Abstracts Data - Speaker Ready Room by One World

Transcription

Abstract ID: 12
Clinical Responses Of Metastatic Melanoma Using Adoptive Transfer Of â€œYoung
Author List
1. Additional Author: Michal Besser
2. Presenting Author: Avi Treves
3. Additional Author: Jacob Schachter
Submitter's Presentation Preference
Oral Sessions
Accepted Presentation Preference
Oral Sessions
Status
Accepted
Presentation Time / Poster No.
October 25, 2012 @ 02:40 PM
Consider for E-poster?
Yes
General Information
General Attendee
Abstract History
This material has not been presented at a national or international meeting.
Abstract Category
Clinical development
Uploaded Files
none
Summary
Introduction
Adoptive cell therapy (ACT) utilizing Tumor Infiltrating Lymphocytes (TIL) has developed into a promising approach for
the treatment of metastatic melanoma patients. We have modified the standard TIL generation procedure and used
short-term cultured, unselected TIL (â€œYoung-TILâ€•) for treatment, as short culture periods were shown to correlate
with clinical response and significantly simplify the laboratory process. In addition, patients received lymphodepleting
chemotherapy and high-dose bolus Interleukin-2.
Methods
Ninety patients were enrolled to the study and Young-TIL cultures were successfully generated for 81 patients (90%).
Twenty-three patients were dismissed from the study, mainly due to clinically deterioration, resulting in a total drop-out
rate of only 26%, compared to 70% in previous TIL ACT. Fourteen patients will complete their treatment shortly and 53
patients have been evaluated. At the time of treatment all patients were refractory to prior IL-2 based therapy and mainly
staged M1c (76%). Eight patients had CNS involvement.
Results
Twenty-three treated patients (=43%) achieved clinical responses, including six complete remissions (CR) and 17 partial
responses (PR). Five patients with brain metastasis showed responses (1 CR and 4 PR). Thirteen additional patients
demonstrated disease stabilization (SD). There was a significant correlation between clinical response and overall survival
(OS) (p<0.001). Non-responding patients had a median OS of 5.4 months, whereas the median OS for complete and partial
responders has not been reached yet. 70% of the responders are alive two years after treatment. Side effects were transient
and manageable. The positive correlation between short TIL culture duration and clinical response was clearly
demonstrated.
Conclusion
We report here that treatment with Young-TIL can mediate tumor regression in 43% of metastatic melanoma patients with
manageable toxicity. Multi-institutional trials are crucial to support the widespread application of this promising approach.
Financial Disclosure (Avi Treves)
Have a financial arrangement or affiliation with commercial companies whose products may be mentioned in this material?
No
Non-Exclusive License
FDA Disclosure
Cleared:Yes
Keywords
melanoma
immunotherapy
adoptive cell therapy
None
Abstract ID: 13
Ethnographic Mapping Identifies A Feasible Venue For A Community Evaluation Of Self-Sample HPV Testing
With Cytology Triage Among Latina Immigrant Screening Non-attendees In Harris County, Texas
Author List
1. Presenting Author: Jane Montealegre
2. Additional Author: Patricia Mullen
3. Additional Author: Maria Jibaja-Weiss
4. Additional Author: Michael Scheurer
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
Consider for Resident Research Awards?
N/A
Abstract History
Abstract Category
Cancer epidemiology, behavioral science, intervention and outcomes research
Uploaded Files
none
Summary
Introduction
Self-sample human papillomavirus (HPV) testing with clinic-based cytology triage targeted among screening
non-attendees (i.e., women who never or sporadically attend for Pap testing) may be a strategy to increase the population
coverage of current cervical cancer screening programs. A significant challenge to its implementation in the U.S., however,
is to find an effective strategy to identify screening non-attendees and connect high-risk HPV positive women with an
organized cervical cancer screening program for follow-up. Here we describe our identification of productive and feasible
venues for reaching Latina immigrant screening non-attendees in Harris County, Texas for a pilot community evaluation of
self-sample HPV testing with cytology triage.
Methods
We conducted ethnographic mapping to create a list of candidate venues where medically-underserved Latina immigrants
interface with the healthcare system. This was an iterative process that drew from eclectic data sources, including a review
of the scientific literature, interviews with immigrant women, and field observations at select venues. We also consulted
researchers and staff at candidate venues to assess the feasibility of partnering with the venues for the pilot study. Venues
were evaluated based on the observed proportion of venue attendees who were Latina immigrant women and who lacked a
medical home; availability of private space; complexity of the administrative approval process; and willingness of venue
leadership and staff to accommodate pilot study activities.
Results
Candidate venues were: Women, Infants, and Children (WIC) Centers; County Hospital District eligibility centers,
emergency rooms, and community clinics; migrant clinics; health fairs; immunization clinics; and organizations that we
termed community health referral agencies (CHRA). CHRAs are community-based organizations that assist
medically-underserved immigrants with on-site health assessments and linkage to available health services. CHRAs were
selected as finalists given the large proportion of their clients who lack a medical home and who are Latina immigrant
women, as well as their generally expedited administrative approval process. Ultimately, for the pilot study, we established
a partnership with a CHRA at the Mexican Consulate.
Conclusion
Through ethnographic mapping, we identified sites where medically-underserved Latina immigrant women interface with
the public healthcare system. While there is a precedent for utilizing the other types of venues, CHRAs may be an untapped
resource for upstream interventions targeting the medically-underserved, given that their clients are individuals without a
medical home. Additionally, they generally involve an expedited approval process, which makes them feasible for pilot
studies.
Financial Disclosure (Jane Montealegre)
No
FDA Disclosure
Cleared:Yes
Keywords
immigrants
medically-underserved
ethnographic mapping
Human Papillomavirus
Abstract ID: 14
Oral siRNA Delivery System For The Treatment Of Colon Cancer
Author List
1. Presenting Author: Diane Forbes
2. Additional Author: Mar Creixell
3. Additional Author: Hannah Frizzell
4. Additional Author: Nicholas Peppas
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Translational, pre-clinical product development
Uploaded Files
none
Summary
N/A
Introduction
Potential siRNA-based therapeutics for the treatment of cancer and other diseases are limited by delivery challenges. While
most siRNA delivery strategies in clinical trials rely on injections, oral administration may be able to improve patient
comfort while providing an effective treatment for diseases including colon cancer. The challenges of oral administration
include protecting the therapeutic agent through the GI tract, allowing for cellular uptake, and then promoting endosomal
escape and release of siRNA into the cytosol. In this work, we propose polycationic hydrogel nanoparticles protected by
alginate matrices which may be used as carriers to overcome these challenges in order to delivery siRNA specifically to the
colon for the treatment of colon cancer.
Methods
Crosslinked, pH-responsive polymer nanoparticles composed of 2-(diethylamino) ethyl methacrylate, poly(ethylene glycol)
methyl ether methacrylate, tetraethylene glycol dimethacrylate, and hydrophobic methacrylate monomers were synthesized
using Activators ReGenerated by Electron Transfer Atom-Transfer Radical Polymerization (ARGET ATRP). The
nanoparticles were encapsulated in an alginate matrix with calcium ions as a crosslinking agent to provide colon-targeted
oral delivery of the siRNA. Nanoparticles are released from the alginate matrix following matrix degradation and erosion
by colonic bacteria; fluorescently labeled nanoparticles were synthesized to analyze release under simulated intestinal
conditions.
Results
Using hemolysis of red blood cells as a measure of endosomal membrane disruption, the nanoparticles demonstrate strong
membrane disruption at acidic pH 6.5 (endosomal pH) but not at pH 7.4 (extracellular pH). The ARGET ATRP
nanoparticles also have pH-responsive swelling from ~115nm at low pH to ~160 nm at high pH, according to dynamic
light scattering. Very low cytotoxicity was observed for both cancerous and non-cancerous cells types, and cytotoxicity
was correlated with hemolysis at pH 7.4. The positive surface charge of the nanoparticles measured as zeta potential
promotes complexation of the cationic carrier with the negatively charged siRNA.
Conclusion
The low cytotoxicity and strong membrane disruption activity of the pH-responsive ARGET ATRP nanoparticles are
critical properties for an effective siRNA carrier. Upon encapsulation in the non-toxic, biodegradable alginate matrix, the
two-part system may be able to meet the challenges of oral delivery to provide an improved treatment strategy for colon
cancer. Acknowledgements: National Science Foundation (CBET 10-33746), National Science Foundation Graduate
Research Fellowship to DCF (DGE-1110007)
Financial Disclosure (Diane Forbes)
No
FDA Disclosure
Cleared:Yes
Keywords
drug delivery
siRNA
oral delivery
colon cancer
Abstract ID: 15
Investigating The Role Of DNA Repair-coupled Chromatin Assembly In DNA Damage Checkpoint Recovery
Author List
1. Presenting Author: Ting-Hsiang Huang
2. Additional Author: Jessica Tyler
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer biology and genetics
Uploaded Files
none
Summary
N/A
Introduction
Genomic DNA damage, which activates and coordinates with several signaling molecules, leads to genomic instability that
is a threat to cell survival in the absence of proper repair. To this end, eukaryotes have developed several sophisticated
mechanisms to regulate repair pathways in response to DNA double-strand breaks (DSBs). However, we know very little
about how DNA break repair occurs in chromatin in which DNA is packaged within the cell. While chromatin functions to
organize DNA, it also creates barrier that inhibits fundamental DNA processes such as allowing access for the repair of
DSBs. Recent reports in yeast have shown chromatin structure around a DNA lesion is altered and remodeled by histone
chaperones and other modifiers. Our studies further indicate that the histone chaperone Asf1 that promotes acetylation of
histone H3 on lysine 56 is important for chromatin reassembly and checkpoint recovery after DNA damage repair in
budding yeast. Given that there is a high level of conservation of DNA repair processes and chromatin structure in
eukaryotes, we expect the similar phenomenon will also be observed in mammalian cells after DNA damage.
Methods
To examine whether the mechanism of DNA damage checkpoint recovery is conserved from yeast to mammals, I will
utilize a novel HO-endonuclease inducible mammalian DSB repair system to induce a DSB per cell efficiently and
checkpoint activation at specific loci followed by DNA repair.
Results
In terms of this unique system, histone dynamics in chromatin structure close to DNA lesions as well as its relevance for
checkpoint recovery can be explored.
Conclusion
Furthermore, detailed mechanisms and novel molecules involved in DNA repair initiation, termination, and checkpoint
recovery will also be investigated in this study.
Financial Disclosure (Ting-Hsiang Huang)
No
FDA Disclosure
Cleared:Yes
Keywords
chromatin
histone chaperone
DNA damage
checkpoint recovery
Abstract ID: 16
ERBB3 (HER3) Is A Key Sensor In The Regulation Of ERBB-mediated Signaling In Both Low And High
ERBB2(HER2) Expressing Cancer Cells.
Author List
1. Presenting Author: Byung-Kwon Choi
2. Additional Author: Zhiqiang An
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
This Material has been published or accepted for publication.
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Aberrant expression and activation of EGFR and ERBB2 (HER2) have been successfully targeted for cancer therapeutics.
Recent evidence from both basic and clinical studies suggests that ERBB3 (HER3) serves as a key activator of downstream
signaling through dimerization with other ERBB proteins and plays a critical role in the widespread clinical resistance to
EGFR and HER2 targeting cancer therapies. As a result, HER3 is actively pursued as an antibody therapeutic target for
cancer. Ligand binding is thought to be a prerequisite for heterodimerization of HER3 with other ERBB proteins, which
results in phosphorylation of its c-terminal tyrosine residues and activation of downstream AKT and MAPK signaling
pathways.
Methods
To monitor the cell proliferation of MCF7 cells under the treatment of anti-HER2 antibody (HER2Mab), we employed
xCelligence instrument (Roche). To investigate the changes of HER2/HER3 interactions in MCF7 and MCF7-HER2 cells,
we performed in situ proximity ligation assay (PLA) (Olink). And also we performed western blot analysis for detecting
total and phosphor-form of HER2, HER3, AKT and ERK in the cells. We employed NanoPro immnofluidic assay for
further verification of AKT phosphorylation in the cells.
Results
In this study, we report that an anti-HER2 monoclonal antibody (HER2Mab), which blocks HER2 dimerization with
HER3, induces HER3 dimerization with EGFR in both low and high HER2 expressing cancer cells. Treatment of the low
HER2 expressing MCF7 cancer cells with HER2Mab promoted cell proliferation and migration in the absence of HER3
ligand stimulation. Follow-up studies revealed that HER2Mab induced HER3 signaling via EGFR/HER3
heterodimerization and activation of downstream AKT signaling pathways.
Conclusion
In conclusion, the equilibrium of dimerization among the ERBB proteins can be perturbed by HER2Mab and HER3 plays a
key role in sensing the perturbation. This study underlines the complexity of targeting ERBB signaling for cancer therapy
and provides a mechanistic rationale for combination therapy to overcome drug resistance when targeting the ERBB
signaling pathway for cancer treatment.
Financial Disclosure (Byung-Kwon Choi)
No
FDA Disclosure
Cleared:Yes
Keywords
Anti-HER2 antibody
EGFR
ERBB2/HER2
ERBB3/HER3
Abstract ID: 17
Pumilio Regulates EMT And The TGFÎ²/BMP Pathway In Cancer Cells And During Early Development
Author List
1. Presenting Author: Vanessa Damoulis
2. Additional Author: Tharun Paruchuri
3. Additional Author: Amanda Prechtl
4. Additional Author: Gray Pearson
5. Additional Author: James Amatruda
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Limitless replicative potential is one of the hallmarks of cancer, suggesting that there is a rare community of cells, the
â€˜cancer stem cells,â€™ which possess the potential to self-renew and drive tumorigenesis. We are interested in how the
molecular programs maintaining stem cell identity are misregulated and exploited by cancer cells to promote growth,
survival and metastasis. We have identified novel zebrafish homologs of Pumilio, a putative stem cell regulator implicated
in development, organogenesis and cancer. Pumilio family proteins are RNA-binding proteins that act as translational
repressors, however their role in vertebrates and direct functional targets have yet to be elucidated.
Methods
Homologs of Pumilio family proteins have not previously been described in zebrafish. We chose to use this powerful
vertebrate model system to assess the role of Pumilio in embryogenesis and stem-cell maintenance. By using the tools
readily available to manipulate and analyze gene expression and function in vivo we were able to define a role
for Pumilio.
Results
We performed morpholino antisense knockdown of the two zebrafish paralogs and found these genes have non-redundant,
essential roles in early vertebrate development. Pumilio morphants display early dorsal-ventral patterning defects as well as
impaired gastrulation. This led us to investigate a role for Pumilio in the epithelial-to-mesenchymal transition (EMT) of
cells, as EMT is necessary to allow for the cell movements required for gastrulation. Expression of e-cadherin is increased
while n-cadherin is decreased in morphants suggesting EMT is inhibited. Additionally, siRNA of Pumilio in human breast
cancer cells blocks the ability of cells to undergo EMT. To understand how Pumilio regulates gastrulation and EMT we
investigated its targets. Members of the TGFÎ²/BMP pathway, most notably Activin Receptors (ACVR), are predicted
targets from in silico and RNA-immunoprecipitation experiments in vitro. Our in vivo
experiments validate AVCR1b as a target for translational repression by Pumilio and also show changes in TGFÎ²/BMP
pathway members in morphant embryos. This regulation of the TGFÎ²/BMP pathway is likely how Pumilio acts to control
both EMT and dorsal-ventral patterning in early vertebrate embryos.
Conclusion
Our current model is that Pumilio acts to control gastrulation through regulating EMT and the TGFÎ²/BMP pathway.
Additionally, it plays a novel role in dorsal-ventral patterning during early embryogenesis. Ongoing studies will examine
the direct functional targets of Pumilio, as well as its role in tumorigenesis and the initiation of metastasis.
Financial Disclosure (Vanessa Damoulis)
No
FDA Disclosure
Cleared:Yes
Keywords
Pumilio
EMT
TGFÎ²/BMP
Development
Abstract ID: 19
Mechanism of NF-ÎºB And IRF3 Activation by MAVS in RIG-I Antiviral Pathway
Author List
1. Presenting Author: Jueqi Chen
2. Additional Author: Siqi Liu
3. Additional Author: Zhijian Chen
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 02:15 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
Introduction
RIG-I antiviral pathway plays a pivotal role in innate immune response against RNA viruses. Upon virus infection, viral
RNA in the cytoplasm is detected by the RIG-I family of receptors, which activates MAVS (mitochondrial antiviral
signaling), an adaptor protein localized on the mitochondrial outer membrane. MAVS in turn leads to the activation of two
transcription factors, NF-ÎºB and IRF3. NF-ÎºB and IRF3 then translocate to the nucleus where they coordinately induce
type-I interferons and proinflammatory cytokines, which suppress viral replication and facilitate further adaptive immune
responses to eliminate viral infection. However, the exact mechanism of NF-ÎºB and IRF3 activation by MAVS is still
largely unknown. Identifying the key players in this pathway will help us explore novel therapeutic targets for infectious
diseases caused by RNA viruses. Moreover, given the fact that approximately 12% of worldwide cancers are closely
associated with virus infection, understanding the innate immune mechanisms against RNA viruses will be beneficial for
prevention and treatment of many types of cancer.
Methods
Our lab has recently developed a cell-free system to specifically study NF-ÎºB and IRF3 activation downstream of MAVS.
In this system, addition of mitochondria isolated from virus-infected cells activates NF-ÎºB and IRF3 in the cytosolic
extracts.
Results
Using this system, we identify three E3 ligases that are crucial for both NF-ÎºB and IRF3 activation. Live cell experiments
using lentivirus-driven RNAi knockdown and rescue cell lines suggest that these E3 ligases play redundant roles in this
pathway. Moreover, we found that MAVS recruits these E3 ligases to the mitochondria upon virus infection, and together
they form large aggregates to activate the downstream signaling. Using fractionation and cell-free system, we also
identified E2 enzymes that are essential for NF-ÎºB and IRF3 activation by MAVS.
Conclusion
In summary, after virus infection, MAVS utilizes multiple ubiquitination signaling pathways to trigger NF-ÎºB and IRF3
activation. These redundant pathways not only amplify the antiviral signal, but also serve as backup systems against
specific viruses that can degrade components in antiviral pathways. Currently we are trying to identify other components
that function downstream of these E3 ligases, such as potential ubiquitination targets. Our final goal is to dissect the
detailed mechanism of the whole pathway.
Financial Disclosure (Jueqi Chen)
No
FDA Disclosure
Cleared:Yes
Keywords
Antivirus
NF-ÎºB
MAVS
Ubiquitination
Abstract ID: 21
A Novel Signaling Process And Biochemical Mechanism Regulating Cellular Behavior Through Actin Filament
Disassembly
Author List
1. Presenting Author: Ruei-Jiun Hung
2. Additional Author: Jonathan Terman
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Human cancers share a small number of well-characterized cellular attributes including the ability to regulate proliferation,
replicate endlessly, avoid programmed death, promote angiogenesis, and mobilize throughout the body. However, the
molecular mechanisms that underlie these cellular behaviors are incompletely understood, prompting us to investigate how
our research advances into the molecular and biochemical mechanisms controlling cell growth, motility, and navigation
might offer new strategies for cancer prevention, diagnosis, and treatment. In particular, Semaphorins and their Neuropilin
and Plexin receptors have recently emerged as new targets for cancer research because they are one of the largest families
of extracellular proteins regulating these cellular behaviors. Furthermore, a new oncogene named MICAL has been
identified and we find that the MICALs are Redox enzymes that mediate Semaphorin signaling. Specifically, our recent
results reveal that Mical provides a long-sought-after direct link between Semaphorins and the modification of the actin
cytoskeleton; the structure underlying many aspects of normal and cancer cell behavior. Our results reveal that Mical
binds to actin and utilizes its Redox enzymatic activity to directly disassemble actin filaments, but the mechanisms by
which Mical affects actin disassembly are unknown.
Methods
Biochemical chromatography approaches, mass spectrometric analyses, total internal reflection fluorescence microscopy
imaging and Drosophila models.
Results
Employing biochemical chromatography approaches and mass spectrometric analyses, we have now found that Mical adds
16 Da (the equivalent of one oxygen) to an actin amino acid residue. Mutagenesis studies in vitro and in vivo confirmed
that Mical induced actin disassembly occurs through oxidation of a single actin amino acid, which is phylogenetically
conserved from flies to humans and is also conserved among all fly and human actins including muscle and cytoplasmic
actins. This Mical-modified amino acid residue lies within the D-loop of the subdomain 2 portion of actin, a region that
mediates actin-actin contacts and polymerization. Further, using total internal reflection fluorescence microscopy
(TIRFM) analysis, our results reveal that Mical cuts individual actin filaments into multiple smaller pieces, indicating that
Mical-mediated oxidation of actin disrupts the association between individual actin monomers.
Conclusion
Thus, our results uncover a new, oxidation-dependent signaling pathway that selectively regulates actin dynamics through
a specific post-translational modification of an amino acid residue present in actin. Furthermore, these novel mechanisms
of action aid our understanding of inhibitory cell responses such as contact inhibition, first described close to 100 years ago
and immediately suggest new ways to prevent the motility and spread of cancer cells.
Financial Disclosure (Ruei-Jiun Hung)
No
FDA Disclosure
Cleared:Yes
Keywords
actin cytoskeleton
semaphorin
Mical
cell movement
Abstract ID: 22
Reconstitution Of An Argonaute-dependent Small RNA Biogenesis Pathway Reveals A Handover Mechanism
Involving The RNA Exosome And The Exonuclease QIP
Author List
1. Presenting Author: Zhihong Xue
2. Additional Author: Haiyan Yuan
3. Additional Author: Jinhu Guo
4. Additional Author: Yi Liu
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
0.jpg
Summary
N/A
Introduction
During past few years, biologists have identified hundreds of genes that encode small RNAs (sRNAs). These sRNAs, as
negative regulators of gene expression, are involved in many cellular processes. Since cancer is the consequence of
disordered genome function, many sRNAs show abnormal expression pattern in cancerous tissue. Argonaute proteins are
required for the biogenesis of some sRNAs, including the PIWI-interacting RNAs and some microRNAs. How Argonautes
mediate maturation of sRNAs independent of their slicer activity is not clear. The maturation of the Neurospora
microRNA-like sRNA, milR-1, requires the Argonaute protein QDE-2, Dicer, and QIP.
Methods
We reconstitute this Argonaute-dependent sRNA biogenesis pathway in vitro and discover that the RNA exosome is also
required for milR-1 production.
Results
Our results demonstrate that QDE-2 mediates milR-1 maturation by recruiting exosome and QIP and by determining the
size of milR-1. The exonuclease QIP ï¬•rst separates the QDE-2-bound pre-milR-1 duplex and then mediates 3â€™to
5â€™ trimming and maturation of pre-milRNA together with exosome using a handover mechanism. In addition, exosome
is also important for the decay of sRNAs.
Conclusion
Together, our results establish a biochemical mechanism of an Argonaute-dependent sRNA biogenesis pathway and critical
roles of exosome in sRNA processing. This study will shed light on the regulation of sRNAs in cellular processes.
Financial Disclosure (Zhihong Xue)
No
FDA Disclosure
Cleared:Yes
Keywords
Argonaute QDE-2
Exosome
Exonuclease QIP
miRNAs
Abstract ID: 23
Transcriptomine, The Nuclear Receptor Transcriptome Database
Author List
1. Additional Author: Scott Ochsner
2. Additional Author: Chris Watkins
3. Additional Author: Apollo Mcowiti
4. Additional Author: Yolanda Darlington
5. Additional Author: Michael Dehart
6. Additional Author: David Steffen
7. Additional Author: Lauren Becnel
8. Presenting Author: Neil McKenna
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Nuclear receptors (NRs), their ligands and coregulators control the expression of a large number of genes with critical roles
in the genesis and progression of myriad cancers, including those of the breast, prostate and ovary. A thorough
understanding of the ligand and tissue-specific regulation of these genes is widely accepted as essential both to improving
the efficacy of existing NR-based therapeutics such as Tamoxifen, and to developing novel ones. The NR signaling field
has generated a wealth of genome-wide expression data points, but due to deficits in their accessibility, annotation and
integration, the full potential of these studies has not yet been realized.
Methods
We searched public gene expression databases and MEDLINE for global transcriptomic datasets relevant to NRs, their
ligands and coregulators. We carried out extensive, deep re-annotation of the datasets using controlled vocabularies for
RNA Source and regulating molecule, and resolved disparate gene identifiers to official gene symbols to facilitate
comparison of fold changes and their significance across multiple datasets.
Results
We assembled these data points into a database, Transcriptomine (www.nursa.org/transcriptomine), that allows for
multiple, menu-driven querying strategies of this transcriptomic "superdataset", including single & multiple genes, Gene
Ontology (GO) terms, disease terms and uploaded custom gene lists. Experimental variables such as regulating molecule,
RNA Source, as well as fold-change and p-value cutoff values can be modified, and full data records can either be browsed
or downloaded for downstream analysis. We demonstrate the utility of Transcriptomine as a hypothesis generation and
validation tool using in silico and experimental use cases.
Conclusion
Our resource empowers users to instantly and routinely mine the collective biology of millions of previously disparate
transcriptomic data points. By incorporating future transcriptome-wide datasets in the NR signaling field, we anticipate
Transcriptomine developing into a powerful resource for cancer research communities in Texas and further afield. 
Financial Disclosure (Neil McKenna)
No
FDA Disclosure
Cleared:Yes
Keywords
Nuclear receptors
Transcriptomics
Microarray
Bioinformatics
Abstract ID: 24
Development Of Therapeutics Targeting Truncated Adenomatous Polyposis Coli (APC) For The Selective Killing
Of Colorectal Cancer Cells
Author List
1. Presenting Author: Lu Zhang
2. Additional Author: Ugur Eskiocak
3. Additional Author: Bruce Posner
4. Additional Author: Jerry Shay
5. Additional Author: Woodring Wright
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Adenomatous polyposis coli (APC) is a multifunctional tumor suppressor mutated in over 80% of colon tumors and its
mutation is believed to be one of the earliest events that contribute to colon cancer initiation [1, 2]. APC has been
implicated in the negative regulation of the canonical Wnt signaling pathway, cell cycle control, cell migration,
differentiation, and apoptosis. Nevertheless, the precise roles of APC in colon cancer progression remain unclear. Over
90% of APC mutations result in truncated proteins that lack microtubule-binding and EB-1 binding motifs, among which
termination mutations at codons 1309 and 1450 occur the most frequently [2]. There is mounting evidence that these
truncated APC proteins play a dominant role in the initiation and/or progression of colon cancer as opposed to being a
recessive/loss of function change[3-5]. Although defects in APC occur in a high fraction of colon cancer cases, there are
currently no therapeutic agents targeting APC truncations. As part of our efforts to elucidate the molecular underpinnings
of colon cancer tumorigenesis, our lab has developed a unique series of immortalized human colonic epithelial cell
(HCEC) lines. We have made derivatives with ectopic expression of the most commonly observed APC truncations found
in patients. We have utilized these isogenic cell lines with defined genetic alterations to identify small molecules that are
selectively toxic to HCECs with APC truncations while sparing normal HCECs.
Methods
A primary toxicity screen was carried out with the UT Southwestern Medical Center 200K small molecule compound
library using HCECs with TP53 and APC knockdowns, as well as ectopic expression of oncogenic KRASV12and
truncated APC1309. Counter screens were performed in isogenic HCECs lacking the APC1309 mutation but retaining
KRASV12, TP53 and APC knockdowns, as well as normal HCECs. Dose response studies were also performed in
authentic colon cancer cell lines HCT116 and DLD1 harboring wild type and truncated APC, respectively.
Results
Two selectively toxic lead compounds have been identified from this screen with IC50s of 63nM and 131nM, respectively
in DLD1 cells. These two compounds have little effect on HCT116 cells or normal HCEC cells.
Conclusion
Our compound screen has identified two lead compounds that are selectively toxic towards colon cancer cells with APC
truncations. These lead compounds and their analogs may represent a novel strategy for the treatment of colon cancer.
Financial Disclosure (Lu Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
colorectal cancer
Adenomatous Polyposis Coli
compound screen
drug development
Abstract ID: 25
Aneuploid Human Colonic Epithelial Cells Are Sensitive To AICAR-induced Growth Inhibition Through
Epidermal Growth Factor Receptor Degradation
Author List
1. Presenting Author: Peter Ly
2. Additional Author: Sang Kim
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Trisomy for chromosome 7 is frequently observed as an initiating event in sporadic colorectal cancer. Although unstable
chromosome numbers and recurrent aneuploidies drive a large fraction of human cancers, targeted therapies selective to
pre-neoplastic trisomic cells are non-existent. We have previously characterized a trisomy 7 cell line (1CT+7)
spontaneously derived from normal diploid human colonic epithelial cells that aberrantly expresses the epidermal growth
factor receptor (EGFR, chromosome 7p11). Recent studies identified AICAR as a pharmacological inhibitor of aneuploid
murine fibroblast proliferation.
Methods
Here, we use a variety of cell-based assays, western blot analyses, and immunohistochemistry to elucidate the effects of
AICAR on HCECs and human colorectal cancer cell lines.
Results
We report that AICAR induces profound cytostatic and metabolic effects on 1CT+7 cells but not their isogenic diploid
counterpart. Dose-response experiments indicate that 1CT+7 cells are four-fold preferentially sensitive to AICAR
compared to diploid cells. Unexpectedly, treatment of 1CT+7 cells with AICAR led to a reversible 3.5-fold reduction
(p=0.0025) in EGFR overexpression. AICAR-induced depletion of EGFR protein can be abrogated through
inhibition of the proteasome with MG132. AICAR also heavily promoted EGFR ubiquitination in cell-based
immunoprecipitation assays, suggesting enhanced degradation of EGFR protein mediated by the proteasome. Moreover,
treatment with AICAR reduced EGFR protein levels in a panel of human colorectal cancer cells in vitro and in xenograft
tumors in vivo.
Conclusion
Our data collectively supports the pharmacological compound AICAR as a novel inhibitor of EGFR protein abundance and
as a potential anti-cancer agent for aneuploidy-driven colorectal cancer.
Financial Disclosure (Peter Ly)
No
FDA Disclosure
Cleared:Yes
Keywords
Aneuploidy
Chromosomal Instability
EGFR
Trisomy
Abstract ID: 26
Nuclear Export Inhibition Through Covalent Conjugation And Hydrolysis Of Leptomycin B By Crm1
Author List
1. Presenting Author: Qingxiang Sun
2. Additional Author: Youcai Hu
3. Additional Author: Yazmin Carrasco
4. Additional Author: John Macmillan
5. Additional Author: Yuhmin Chook
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 02:30 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The polyketide natural product known as Leptomycin B is a potent, specific and widely used inhibitor of CRM1-mediated
nuclear export. CRM1 (Chromosome Region Maintenance 1 protein/Exportin1/Xpo1) transports hundreds of proteins and
ribonucleoprotein complexes out of the cell nucleus through recognition of their leucine-rich nuclear export signals
(NESs).
Methods
Here we present 1.8-2.0 Ã… resolution crystal structures of CRM1 bound to Leptomycin B (LMB) and to related
inhibitors Anguinomycin A (AGA) and Ratjadone A (RJA).
Results
The compounds make extensive hydrophobic and electrostatic interactions to fill ~70% of the NES-binding groove of
CRM1, explaining their inhibition of NES binding. Comparison of inhibitor bound CRM1 grooves to empty and
NES-bound grooves suggests structural plasticity of the site. In the complexes, the inhibitors are conjugated to a reactive
cysteine residue and their lactone rings have been hydrolyzed to hydroxyl acids, even though hydrolysis of free
Î±,Î²-unsaturated lactones is disfavored. To explore the reaction mechanisms, we made mutations in the CRM1 groove
resulting in a trapped a reaction intermediate that identified three basic residues driving lactone hydrolysis through
stabilization of the anionic tetrahedral intermediate and/or the hydroxy acid product.
Conclusion
Therefore, the NES-binding groove of CRM1 is able to catalyze a chemical reaction in addition to binding protein cargos
for transport through the nuclear pore complex. CRM1 may possibly catalyze analogous reactions with other yet
undiscovered biological substrates.
Financial Disclosure (Qingxiang Sun)
No
FDA Disclosure
Cleared:Yes
Keywords
CRM1
Leptomycin B/inhibitor
Hydrolysis/enzyme
Structure
Abstract ID: 27
WNK3 Regulates The Neuronal Splicing Factor Fox-1
Author List
1. Presenting Author: A-Young Lee
2. Additional Author: Melanie Cobb
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
RNA binding feminizing gene on X (RBFoxâ€‘1 or Fox-1) splices pre-mRNAs in a tissue-specific manner. In brain it has
been implicated in autism and other neuronal developmental disorders.With No lysine (K) 3 (WNK3) is highly expressed
in brain, kidney and some other tissues. WNK3 modulates neuronal excitability through control of ion cotransporters.
Duplication or deletion of the genomic location encompassing the WNK3 gene has been found in individuals with neuronal
disorders including autism spectrum disorder (ASD) and glioma.Here, we report a novel action of the protein kinase
WNK3 on the neuronal mRNA splicing factor Fox-1.
Methods
Yeast two-hybrid assay was performed to identify novel WNK3-binding proteins. The interactions were confirmed through
in vitro pull-down assay and cell-based in vivo assay. For functional verification of WNK3-Fox-1 interaction, mRNA
splicing assay, in vitro kinase assay, subcellular fractionation assay, and inmmunofluorescence assay were performed. 
Results
WNK3 binds to a unique region of Foxâ€‘1 and inhibits its splicing activity in a kinase activity-dependent manner. WNK3
phosphorylation of Foxâ€‘1 does not change its RNA binding capacity; instead, WNK3 increases its cytoplasmic
localization, thereby suppressing Fox-1-dependent splicing. 
Conclusion
These findings demonstrate a new role of WNK3 in RNA processing. Considering the implication of WNK3 and Fox-1 in
neurological disorders such as autism and glioma, WNK3 may offer a target for treatment of Fox-1-induced disease.
Financial Disclosure (A-Young Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
Fox-1
WNK3
neuronal excitation
glioma
Abstract ID: 28
Characterization Of Disease-initiating Cells In Two Models Of Myeloproliferative Neoplasms
Author List
1. Presenting Author: Huiyu Yao
2. Additional Author: Yue Ma
3. Additional Author: Lily Huang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Myeloproliferative neoplasms (MPNs) are a phenotypically diverse group of pre-leukemic diseases characterized by
overproduction of one or more of the myeloid cell lineages, and are currently in need of novel therapeutics. The
development of these agents is hindered by the lack of information on MPN-initiating stem cells. We propose to use a
novel set of MPNs models to guide us in identifying MPN-initiating stem cells and key signaling networks therein that
sustain their self-renewal. This information will form the essential knowledge base for designing of better and more
effective therapies.
Methods
Gain-of-function mutations in the JAK2 tyrosine kinase are found in the majority of patients with MPNs, and are sufficient
to cause a similar disease in mice. We utilize a bone marrow transplant model to introduce JAK2(K539I) (K539 resides in
exon 12) and JAK2(V617F), as well as wild-type JAK2 into Balb/C mice. Every two weeks post transplant, blood was
collected from these mice and analyzed.
Results
Mice expressing JAK2 mutants but not wild-type JAK2 exhibited overproduction of myeloid cells, and distinctive subsets
of myeloid cells were overproduced in mice expressing the two JAK2 mutants. In line with clinical data, mice receiving
JAK2(V617F)-transduced bone marrow cells exhibited erythrocytosis and neutrophilic granulocytosis, while recipients of
JAK2(K539I)-transduced cells showed primarily erythrocytosis. We hypothesized that MPN-initiating cells are the
JAK2-targeted hematopoietic stem cells (HSCs). Therefore, we used SLAM markers CD150 and CD48 to identify
long-term HSCs (LT-HSCs) in various hematopoietic compartments. Interestingly, a robust increase in numbers of
LT-HSCs was found in JAK2(K539I) mice, and they are particularly enriched in the Lin-Sca1+c-Kit+ compartment in both
the bone marrow and the spleen compared to the Lin-Sca1-c-Kit+ compartment. In contrast, LT-HSCs from JAK2(V617F)
decreased dramatically in the bone marrow and instead were found in the Lin-Sca1+c-Kit+ compartment in the spleen.
These results suggest that JAK2(K539I) but not JAK2(V617F) enhances LT-HSCs self-renewal. To determine that
LT-HSCs are enriched for MPN-initiating cells, we performed secondary transplantation using Lin-Sca1+c-Kit+ cells from
the bone marrow of JAK2(K539I) mice. Consistent with our hypothesis, 5 of the 6 recipients of GFP+/Lin-Sca1+c-Kit+
cells developed a similar disease 4 weeks post secondary transplantation. In contrast, none of the 6 recipients of
GFP+/Lin-Sca1-c-Kit+ cells from JAK2(K539I) expressing mice developed MPNs.
Conclusion
Our results suggest that MPN-initiating cells are enriched in LT-HSCs, and the differences in re-distribution of LT-HSCs
in mice expressing JAK2V617F vs. exon 12 mutations may contribute to MPNs phenotypic diversity.
Financial Disclosure (Huiyu Yao)
No
FDA Disclosure
Cleared:Yes
Keywords
JAK2
JAK2V617F
myeloproliferative neoplasms
MPN-initiating cells
Abstract ID: 30
Adapting The Spontaneous Canine Osteosarcoma Model For T-cell Therapies
Author List
1. Presenting Author: Melinda Mata
2. Additional Author: Sunitha Kakarla
3. Additional Author: Juan Vera
4. Additional Author: Lisa Wang
5. Additional Author: Cliona Rooney
6. Additional Author: Heather Wilson
7. Additional Author: Stephen Gottschalk
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Osteosarcoma (OS) is the most common primary bone malignancy. The outcome for patients with metastatic/refractory
disease remains poor and new targeted therapies are needed. The use of genetically modified T-cells expressing chimeric
antigen receptors (CAR) against the OS tumor antigen HER2 has shown promise as a targeted cancer treatment in murine
xenograft models. However, these models do not allow for the detailed study of engrafted T-cells in a natural tumor
environment since the mice are immunodeficient. Furthermore, the small size of the animal does not allow for frequent
blood sampling and survival surgeries. OS disease and progression in canines has been shown to mimic human pathology
in terms of tumor location and metastasis to the lungs, making it an ideal model for the preclinical evaluation and
optimization of CAR+ T-cell therapies. The immediate goal of this study is to optimize expansion and transduction of
canine T-cells to express CARs against OS tumor antigens, such as HER2 and FAP, as a prelude to a future clinical study
in canines.
Methods
Results
To activate and expand canine T-cells, canine PBMCs were activated with PHA, irradiated artificial antigen presenting
cells (K562 cells expressing CD80, CD83, CD86, and 4-1BBL), and IL21. Cells expanded on average 3.4 fold (n=9)
within 7 days of co-culture. The majority of cells were CD3+ (mean: 80%) with a mixture of CD8+ and CD4+ T-cell
subsets. Restimulation of T-cells in Grex tissue culture devices with the addition of IL2 resulted in ~60-fold expansion of
cells, generating sufficient number of T-cells for future clinical studies in canines. To determine if we can retrovirally
transduce canine T-cells, T-cells were transduced 3 days post-activation with GALV-pseudotyped retroviral particles
encoding HER2-specific CARs or RD114-pseudotyped retroviral particles encoding FAP-specific CARs. Post
transduction, up to 38% of canine T-cells expressed CARs with no significant difference between GALV- and
RD114-pseudotyped retrovirus-transduced T-cells. HER2-CAR T-cells and FAP-CAR T-cells were able to recognize
HER2+ or FAP+ cell lines as evidenced by the production of canine IFNÎ³ in co-culture assays. In addition, transduced
T-cells were able to kill HER2+ or FAP+ cell lines in 51Cr release cytotoxicity assays.
Conclusion
Our results indicate that it is feasible to activate, expand, and genetically modify canine T-cells. Adapting the canine OS
model for T-cell therapies will not only facilitate their translation into the clinic, but will also allow us to realistically study
how to best combine T-cell therapy with other OS-targeted therapies.
Financial Disclosure (Melinda Mata)
No
FDA Disclosure
Cleared:Yes
Keywords
osteosarcoma
HER2
chimeric antigen receptors
canine
Abstract ID: 32
Deregulation Of Steroid Receptor Coregulator-2 Causes Severe Sub-fertility And Abnormal Hormone
Responsiveness In The Murine Endometrium
Author List
1. Presenting Author: Maria Szwarc
2. Additional Author: Ramakrishna Kommagani
3. Additional Author: San-Pin Wu
4. Additional Author: Sophia Tsai
5. Additional Author: Ming-Jer Tsai
6. Additional Author: Francesco DeMayo
7. Additional Author: John Lydon
8. Additional Author: Bert O'Malley
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Steroid receptor coregulator-2 (SRC-2) is a member of the p160/SRC family of coregulators, which includes SRC-1 and
SRC-3. These coregulators modulate the transactivational potency of both nuclear receptor (NR) and non-NR transcription
factors. Mouse studies demonstrate that SRCs exert diverse regulatory effects in vivo, ranging from modulating mammary
morphogenesis to controlling metabolic homeostasis. Apart from normal physiology, deregulation of these coregulators is
causal for many tissue pathologies. In the case of the endometrium, clinical studies reveal that SRC-2 and SRC-3 levels are
elevated in endometrial biopsies from patients diagnosed with polycystic ovary syndrome (PCOS). Significantly, the
endometrium of PCOS patients displays severe defects in functionality, including cancer susceptibility. Elevated
expression of both coregulators is also found in the hyperplastic and neoplastic endometrium. Collectively, these findings
suggest a causal link between elevated expression of one or both coregulators and the emergence of these endometrial
disorders.
Methods
Using state-of-the-art experimental mouse genetics, we engineered an SRC-2 overexpressor (SRC-2: OE) mouse in which
high levels of human SRC-2 expression are specifically targeted to cells that express the progesterone receptor. Long
term-breeding studies, a decidual response assay, gonadotropin-induced superovulation, and measurement of serum
hormone levels were conducted on SRC-2: OE mice to evaluate fertility status. Uterine response to acute and long-term
estradiol exposure was also examined at the gross morphological and histological level. In parrallel, the proliferative
consequence of reducing endogenous SRC-2 levels in human endometrial cancer (Ishikawa) cells was achieved by
shRNAs delivered by lentiviral transduction.
Results
Although ovulation and serum hormone levels are normal, six month breeding studies show that elevated levels of
endometrial SRC-2 in the SRC-2: OE mouse result in a severe subfertility defect. Compared to wild-type siblings, the
endometrium of adult SRC-2:OE mice is significantly enlarged due to epithelial and stromal hyperproliferation.
Ovariectomy followed by short-and long-term estradiol treatment reveals that SRC-2 markedly potentiates
estradiol-induced uterine epithelial proliferation and stromal edema, suggesting an important role for SRC-2 in the
promotion of unopposed estrogen-action. Importantly, knockdown of SRC-2 levels alone significantly attenuated the
proliferative response of human endometrial cancer cells in culture, implicating a role for this coregulator in endometrial
cancer progression.
Conclusion
We conclude that tight control of SRC-2 levels is mandatory not only for normal endometrial functionality that is required
for pregnancy but also to prevent unscheduled endometrial hyperplasia which can lead to cancer. This research was funded
by NIH grants (U54 HD-07495) and (CA-077530).
Financial Disclosure (Maria Szwarc)
No
FDA Disclosure
Cleared:Yes
Keywords
endometrial cancer
infertility
steroid hormone action
nuclear receptor coactivator
Abstract ID: 33
Development of a highly sensitive molecule-sized T2 contrast agent for targeted molecular imaging of cancer by
MRI
Author List
1. Presenting Author: Todd Soesbe
2. Additional Author: James Ratnakar
3. Additional Author: Zoltan Kovacs
4. Additional Author: A Dean Sherry
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Cancer imaging and diagnosis
Uploaded Files
033_image.jpg
Summary
Introduction
Magnetic resonance imaging (MRI) offers superior anatomic resolution and soft tissue contrast compared to x-ray
computed tomography, making it an excellent tool for cancer prevention studies. It was recently shown that
lanthanide-based Ln3+DOTA chelates (Ln3+ La3+, Gd3+, Lu3+) create enhanced negative contrast (i.e., darkening) in
MRI through the chemical exchange of water molecules. The level of this â€œT2-exchangeâ€• contrast, which adds to the
inherent paramagnetic T2 contrast of the Ln3+ ion, reaches a maximum at a specific water molecule exchange rate. It was
also recently demonstrated that T2-exchange contrast could be increased by several orders of magnitude through simple
linear polymerization of the Ln3+DOTA chelate. We hypothesize that by using these methods a highly sensitive
molecule-sized T2 contrast agent can be created. The transverse relaxivity (r2) would be an order of magnitude greater than
any currently existing contrast agent (e.g., super paramagnetic iron oxide nanoparticles), while retaining the advantages of
using small molecules rather than nanoparticles for improved biological targeting, uptake, and clearing.
Methods
Four different versions of a Dy3+DOTA chelate were synthesized, each having a different water molecule exchange rate at
37 Â°C. The Dy3+ ion was chosen because it has the largest bound water chemical shift (Î”Ï‰) and one of the largest
paramagnetic relaxation enhancements (PRE) of the lanthanides (second only to Gd3+). Both characteristics will maximize
the level of T2 contrast achieved for the monomer structure (r2 approximately 16 s-1 mM-1). The total r2 for each
compound was measured in vitro on a vertical 9.4 T system. Initial in vivo data were taken on an animal 9.4 T system and
used renal uptake due to glomerular filtration in healthy mice to assess the sensitivity of the contrast agent.
Results
The experimental relaxivity data were in excellent agreement with the theoretical Swift-Connick plot of relaxivity (r2)
versus the bound water molecule lifetime (Ï„B), with Dy3+DOTA-(gly)2 giving the highest r2 value at 37 Â°C. A 0.1
mmol/kg intravenous dose of Dy3+DOTA-(gly)2 caused a 60% reduction in the mouse kidney signal at 15 minutes
post-injection.
Conclusion
By using chemical structure to tune the water molecule exchange rate, a highly sensitive T2-exchange MRI contrast agent
has been created. Further work includes polymerization of the agent to increase the sensitivity by up to 100 times, and
attaching molecular targeting groups along the linear backbone of the polymer chain to target specific over-expressed
cancer cell receptors (e.g., NER2/neu and PSMA). These agents have the potential to accurately image the location and
size of cancerous lesions and differentiate between indolent and aggressive forms, thereby performing disease staging
entirely non-invasively.
Financial Disclosure (Todd Soesbe)
No
FDA Disclosure
Cleared:Yes
Keywords
MRI
T2 contrast agent
chemical exchange
targeted molecular imaging
Abstract ID: 34
Impact Of Cancer Associated Fibroblasts And Collagen I Mediated Signals On Bladder Cancer Progression
Author List
1. Presenting Author: Antonina Kurtova
2. Additional Author: Erica Lay
3. Additional Author: Jing Xiao
4. Additional Author: Weiguo Jian
5. Additional Author: David Rowley
6. Additional Author: Seth Lerner
7. Additional Author: Keith Chan
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Metastatic bladder cancer is mostly incurable disease with only 6% overall survival rate; therefore it is crucial to
understand the mechanisms that drive bladder cancer progression. We reported that a higher frequency of tumor-initiating
cells (TICs) in bladder cancer patients correlates with poorer survival outcome and is associated with progression to
invasive disease. Our preliminary results revealed the presence of activated cancer-associated fibroblasts (CAFs),
characterized by co-expression of vimentin, alpha-smooth muscle actin, and tenascin C in close proximity to CD44+ TICs
in muscle invasive bladder cancer. CAFs have been reported to regulate various biological properties of tumor cells, while
little is known about its interaction with TICs and functional role in bladder cancer. In the current study we investigate
whether collagen I secreted by CAFs contribute to the invasive progression and distal metastasis via modulating TICs
behavior.
Methods
To evaluate the functional significance of CAFs and its secreted extracellular matrix (ECM), we co-transplanted CAFs or
collagen I with bladder cancer cells in vivo and analyzed the resulting phenotype of xenograft tumors. To analyze whether
collagen I enhances metastatic lung colonization, bladder cancer cells were injected via tail vein followed by real-time
imaging.
Results
We found that tumors formed from co-transplantation of TICs and CAFs showed higher collagen I deposition and were
unexpectedly smaller than controls. Oncomine gene expression analysis showed that muscle-invasive bladder cancer
expressed higher mRNA levels of collagen I and its receptors: integrins, discoidin domain receptors (DDRs) and Endo180,
than non-invasive bladder cancer, indicating that collagen I may play a role in cancer invasion. We demonstrated that
collagen I as a single ECM component induced tumor phenotype recapitulating the one observed after co-injection of TICs
and CAFs, these include formation of smaller tumors and expansion of TICs. Pre-stimulation with collagen I enhanced
metastatic lung colonization of T24 bladder cancer cells. Molecular analysis of these collagen I stimulated cancer cells
showed up-regulation of collagen receptors such as DDR1 and Endo180, but not integrins. Finally, immunohistochemical
analysis of T24 xenografts confirmed the presence of DDR1+ subpopulation in close proximity to CAFs in the primary
tumor site, with significantly enhanced and widespread expression of DDR1 in corresponding lung metastasis.
Conclusion
These results revealed a crosstalk between CAFs and TICs, likely mediated through collagen I signal in enhancing
metastasis and therefore warrant further analysis of downstream signaling molecules for collagen I. Functional knockdown
of DDR1 may identify potential drug targets to attenuate bladder cancer progression.
Financial Disclosure (Antonina Kurtova)
No
FDA Disclosure
Cleared:Yes
Keywords
bladder cancer
cancer associated fibroblasts
tumor initiating cells
collagen
Abstract ID: 35
Targeting The TBK1/AKT Pathway In Cancer
Author List
1. Presenting Author: Yi-Hung Ou
2. Additional Author: Malia Potts
3. Additional Author: Yazmin Carrasco
5. Additional Author: Michael White
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The goal of my research is to define the immediate downstream effector proteins engaged by TBK1 to support cancer cell
survival and evaluate the consequence of antagonizing TBK1 pathway activation on primary tumor growth and metastasis.
Methods
.
Results
The atypical IKK family member TBK1 plays a pivotal role in the innate immune responses. We have reported that the
RalB/Sec5 effector complex directly recruits and activates TBK1 in this physiological context. Moreover, cancer cells
hijack this RalB/Sec5/TBK1 pathway to deflect apoptosis. In this disease setting, depletion of TBK1 or Sec5 is selectively
toxic. We further show that TBK1 directly activates AKT by phosphorylation of the canonical activation loop and
hydrophobic motif sites independently of PDK1 and mTORC2. A population of AKT is bound to components of the
exocyst complex. Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or
oncogene activation, TBK1 is recruited to the exocyst, where it activates AKT. In cells lacking TBK1, insulin activates
AKT normally, but AKT activation by these exocyst-dependent mechanisms is impaired. Discovery and characterization of
a 6-aminopyrazolopyrimidine derivative, as a selective low nanomolar TBK1 inhibitor, indicates this regulatory arm can be
pharmacologically perturbed independently of canonical PI3K/PDK1 signaling. To identify additional chemical inhibitors
of TBK1, with distinct structural scaffolds and specificity profiles, we carried out a chemical/genetic screen of a large
collection of marine-derived natural products. From this effort, we isolated a pure metabolite, 5SNB-003-11-3, which
directly inhibits TBK1 kinase activity at picomolar concentrations. Here we describe identification and biochemical
characterization of this natural product lead.
Conclusion
.
Financial Disclosure (Yi-Hung Ou)
No
FDA Disclosure
Cleared:Yes
Keywords
Cancer
Oncogenes
Signal transduction
None
Abstract ID: 36
Preliminary Results: Exito! Latino Cancer Research Leadership Training
Author List
1. Additional Author: Amelie Ramirez
2. Additional Author: Kipling Gallion
4. Additional Author: Cynthia Wittenburg
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
exito logo.jpg
Summary
Introduction
Latinos are currently the largest and youngest U.S. minority group, but only 3% of Latinos receive a terminal degree and
the number of Latino researchers in biomedical and behavioral science is even less. Exito! Latino Cancer
Research Leadership Training (Exito!) is a five-year program funded by the National Cancer Institute to
increase the number of Latinos pursuing a doctoral degree and a career in Latino cancer health disparities (CHD) research.
Methods
Each year, up to 20 masterâ€™s-level students and masterâ€™s-level health professionals are selected to participate in the
Exito! program. Exito! has two components: (1) A five-day Summer Institute (SI) where
participants hear from internationally recognized researchers conducting Latino CHD research and receive resources, tips
and motivation to apply to and complete a doctoral program and (2) a 6-month internship to receive mentorship and an
opportunity to conduct research related to Latino CHD.
Results
Thirty-seven individuals have completed the Exito! program. Nearly one-third of these individuals (27%) have
applied to doctoral programs, and 70% of those who have applied have been accepted. Follow-up survey results indicate,
after attending the SI, participants self-efficacy to apply (p<.00), be accepted (p<.00) and complete a doctoral program
increased. Further, after attending the SI, participants reported being more confident they will apply to a doctoral program
in the next year, and are more confident they will pursue a career in CHD research.
Conclusion
Cultural competency is quickly becoming recognized as an important factor in cancer prevention and control research.
Increasing the number of Latinos conducting CHD research is necessary to create effective cancer prevention and control
programs for this population that experiences disproportionate incidence and mortality rates for certain cancers. Programs
such as Exito! are providing the mentorship and encouragement necessary to ensure Latinos obtain a doctoral
degree and conduct culturally effective research and programs as the Latino population continues to grow.
Financial Disclosure (Yi-Hung Ou)
No
FDA Disclosure
Cleared:Yes
Keywords
Latino
Cancer health disparities
Training program
Doctoral degree
Abstract ID: 40
Lactate Dehydrogenase B In Breast Cancer Contributes To Glycolytic Phenotype And Predicts Response To
Neoadjuvant Chemotherapy
Author List
1. Presenting Author: Jennifer Dennison
2. Additional Author: Jennifer Molina
3. Additional Author: Shreya Mitra
4. Additional Author: Ana Maria Gonzalez-Angulo
5. Additional Author: Gordon Mills
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Biomarker/Diagnostic discovery/development
Uploaded Files
none
Summary
Introduction
Although breast cancers are known to be molecularly heterogeneous, their metabolic heterogeneity is less well
characterized and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual
biomarkers in breast cancer.
Methods
mRNA microarray data from breast cancer cell lines were used to identify bimodal genes â€“ those with the highest
potential for robust high/low classification in clinical assays. Using a panel of breast cancer cell lines, expression and
activity of the highest scoring bimodal metabolism gene, lactate dehydrogenase B (LDHB) was quantified and
associated with glycolytic phenotype. The contribution of LDHB to glycolysis was evaluated using MDA-MB-231 and
HCC1937 cell lines with stable lentiviral knockdown of LDHB. mRNA expression of LDHB was evaluated
for association with neoadjuvant chemotherapy response within clinical and PAM50-derived subtypes.
Results
LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Knockdown of LDHB in cell lines
reduced glycolytic dependence, linking LDHB expression directly to metabolic function. LDHB mRNA
expression was positively associated with basal subtype and negatively associated with luminal and HER2 subtypes.
Furthermore, LDHB predicted basal phenotype independently of hormone-receptor (HR) clinical status (OR =
21.3 for HR-positive/HER2-negative and OR = 10.3 for triple-negative). While LDHB expression could
predict basal phenotype, high LDHB expression identified aggressive breast cancer tumors that were primarily but not
exclusively basal. Importantly, high LDHB expression predicted pathological complete response to
neoadjuvant chemotherapy for both hormone receptor (HR) positive/HER2-negative (OR = 4.0, P = .0002) and
triple-negative (OR = 3.0, P = .003) cancers. Consistent with increased response to chemotherapy, LDHB in
basal cancers within the triple-negative group was associated with the proliferative marker CCNB1 (P <
.0001). In multivariate analyses, LDHB predicted response independently of known prognostic biomarkers
including tumor size, HR status, PAM50 basal subtype, and grade.
Conclusion
mRNA expression of LDHB as a single marker predicted glycolytic phenotype in cell lines and response to
neoadjuvant chemotherapy in breast cancers independently of known prognostic biomarkers. These observations support
prospective clinical evaluation of LDHB as a predictive marker of response for breast cancer patients treated
with neoadjuvant chemotherapy.
Financial Disclosure (Jennifer Dennison)
No
FDA Disclosure
Cleared:Yes
Keywords
breast
metabolism
biomarker
chemotherapy
Abstract ID: 41
Salivary mRNAs For Oral Cancer Detection In Oral Cancer Patients In Remission And Oral Lichen Planus
Patients
Author List
1. Presenting Author: Yishing Cheng
2. Additional Author: Lee Jordan
3. Additional Author: Terry Rees
4. Additional Author: Huey-Shys Chen
5. Additional Author: Ole Brinkmann
6. Additional Author: David Wong
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The current five-year survival rate for oral squamous cell carcinoma (OSCC) is around 60% and is one of the lowest
among all major cancer types. Early detection has been emphasized and several non-invasive approaches, including
salivary biomarkers, have been proposed. The levels of seven salivary mRNAs, IL-8, IL-1Î², dual specificity phosphatase 1
(DUSP1), H3 histone family 3A (H3F3A), ornithin decarboxylase antizyme 1 (OAZ1), S100 calcium binding protein P
(S100P) and spermidine/spermine N1-acetyltransferase 1 (SAT1), have been reported significantly elevated in OSCC
patients and suggested as possible OSCC salivary biomarkers. However, the levels of these biomarkers in two high-risk
groups: OSCC patients-in-remission and oral lichen planus (OLP) patients (both with and without symptoms/signs), were
still unknown. The purpose of this pilot study was to compare the levels of these 7 salivary mRNAs in the above mentioned
patient groups with normal controls, to gather data as basis for possible application of these salivary components for oral
cancer detection.
Methods
Twenty-five saliva samples were collected from each of five study groups: newly-diagnosed OSCC; OSCC in-remission;
OLP in disease-active state; OLP in disease-inactive state; and normal controls. Relative quantity (RQ) of these seven
salivary mRNAs in patient groups (OSCC or OLP) to the normal controls were determined by a pre-amplification
RT-qPCR approach with nested gene-specific primers. Results were recorded and analyzed by Bio-Rad CFX96 Real-Time
System. Mean fold changes between each pair of patient vs. control groups were analyzed by Mann-Whitney U test.
Results
RQ of salivary OAZ1, S100P and DUSP1 mRNA were significantly higher in OSCC compared to levels in normal controls
(p=0.003; p=0.003; and p<0.001, respectively), OSCC in-remission (p<0.001; p=0.001; and p<0.001, respectively), OLP
disease-active (p<0.001; p=0.016; and p<0.001, respectively), and OLP disease-inactive (p=0.043; p<0.001; and p<0.001,
respectively). There were no significant differences in the RQ of salivary IL-8, IL-1Î², H3F3A and SAT1 mRNAs in OSCC
compared to normal controls (p=0.093; 0.327; 0.764; and 0.560, respectively). Salivary H3F3A and SAT1 mRNAs were
significantly elevated in OSCC compared to OSCC in-remission (p=0.026 and 0.046), but not to OLP disease-active
(p=0.954 and 0.318) or OLP disease-inactive (p=0.077 and 0.367). Salivary IL-1Î² mRNA was marginally elevated in
OSCC compared to OLP disease-inactive (p=0.049), but not to OLP disease-active or OSCC in-remission (p=0.357 and
0.421).
Conclusion
Salivary mRNA of OAZ1, S100P and DUSP1 are good candidate biomarkers for detecting OSCC development in OSCC
in-remission and in OLP in disease-active or disease-inactive states.
Financial Disclosure (Yishing Cheng)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 42
RHOA-FAK is a Required Signaling Axis for the maintenance of K-RAS-Driven Lung Cancer
Author List
1. Presenting Author: Georgia Konstantinidou
2. Additional Author: Giorgio Ramadori
3. Additional Author: Francesca Torti
4. Additional Author: Pier Paolo Scaglioni
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Non-small cell lung cancer (NSCLC), the most common type of lung cancer, often expresses oncogenic mutations of the
small GTPase K-RAS (mutant K-RAS) in association with inactivating mutations of the CDKN2A locus (which comprises
the p16/INK4a and p14/ARF tumor suppressors). The presence of these mutations is associated with aggressive, therapy
resistant NSCLC. To date, no strategy has been demonstrated effective to unmask molecular vulnerabilities of this type of
tumor.
Methods
Here, we unraveled specific requirements for the maintenance of NSCLC harboring K-RAS mutations by undertaking a
multifaceted approach that employs a mutant K-Ras (K-RasG12D);Ink4a/Arf-/- mouse model of NSCLC and functional
studies in human NSCLC-derived cells.
Results
We have established that the RhoA/focal adhesion kinase (FAK) oncogenic network is specifically deregulated in
high-grade lung cancer in vivo. Suppression of either RHOA or FAK, a downstream effector of RHOA, causes striking
inhibition of tumor growth and apoptosis selectively in lung adenocarcinomas. These data suggest that NSCLCs expressing
mutant K-RAS and deficient for INK4A/ARF are critically addicted to RHOA/FAK signaling.
Conclusion
Our findings provide the rationale for the rapid implementation of personalized targeted therapies with FAK inhibitors in
cancer patients.
Financial Disclosure (Georgia Konstantinidou)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 43
The Combination Of Proteasome Inhibition With Histone Deacetylase Inhibition For Glioblastoma Therapy
Author List
1. Presenting Author: Christa Manton
2. Additional Author: Joya Chandra
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Proteasome inhibition leads to an accumulation of misfolded and abnormal proteins in cells, and has been shown to
selectively kill cancer cells with limited toxicity to normal cells. This therapeutic strategy has been successful in
hematologic malignancies, leading to FDA-approval of the proteasome inhibitors bortezomib and carfilzomib. We seek to
determine whether proteasome inhibition is an effective therapeutic approach for glioblastoma. Glioblastoma multiforme
(GBM) is a deadly disease with a median survival time of 15 months. In this study, we examined the single agent efficacy
of two proteasome inhibitors in GBM; the reversible, FDA-approved inhibitor bortezomib, and the irreversible inhibitor
marizomib. We also tested the potency of these inhibitors combined with histone deacetylase inhibitors (HDACi), a
combination that is synergistic in hematologic malignancies. We used multiple HDACi to determine which HDACs must
be inhibited for the most potent apoptotic effect. Additionally, we looked at the effect of the combination on cellular
factors that may explain a synergistic effect, such as histone acetylation and mRNA levels of proteasome subunits. 
Methods
Cells treated with proteasome inhibitors or the combination with HDACi were stained with propidium iodide and analyzed
by flow cytometry for DNA fragmentation, a marker of apoptosis. Synergy of the combinations was determined using
CalcuSyn software to calculate combination index (CI) values. Proteasome activities were measured during a timecourse of
inhibitor treatment using specific substrates for proteasome catalytic activities. Histone acetylation after treatment with the
combination was assessed by Western blot. Proteasome subunit beta 5 mRNA levels were measured by q-PCR after
treatment with individual inhibitors or the combination. 
Results
Despite its reversible nature, bortezomib led to longer-lasting proteasome inhibition and a stronger induction of cell death
than the irreversible marizomib. Both bortezomib and marizomib synergized most potently with the pan-HDACi vorinostat
in GBM cells. There was also some synergy with the pan-HDACi panobinostat, but not much of an effect with the class I
HDACi entinostat. The most synergistic doses for each drug involved much lower doses of bortezomib than marizomib (10
nM versus 100 nM, respectively, when combined with vorinostat). 
Conclusion
This study unexpectedly reveals an increased potency of the reversible inhibitor bortezomib over the irreversible
marizomib. Furthermore, lower doses of bortezomib were able to synergize with vorinostat to the same extent as much
higher doses of marizomib. This study revealed a strongly synergistic action of proteasome inhbitors combined with
HDACi, giving rationale for their use in future in vivo and clinical studies. 
Financial Disclosure (Christa Manton)
No
FDA Disclosure
Cleared:Yes
Keywords
proteasome
glioblastoma
HDACi
bortezomib
Abstract ID: 44
Texture And Density Extracted From Computed Tomography Imaging Can Quantify The Change Of Normal Lung
Tissue In Response To Radiation
Author List
1. Presenting Author: Shane Krafft
2. Additional Author: Laurence Court
3. Additional Author: Tina Briere
4. Additional Author: Mary Martel
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Figure 1.jpg
Summary
Introduction
Approximately 20-30% of patients treated with standard radiotherapy (4 to 6 weeks duration) for non-small-cell lung
cancer experience severe radiation-induced lung injury. The potential exists to identify and quantify changes within the
normal lung during treatment using CT imaging features (biomarkers) such as texture and density. The goal of this study
was to determine if selected CT features correlate with dose to the lung and if features analyzed early during treatment are
predictive of toxicity outcome later during therapy.
Methods
A retrospective analysis was performed utilizing pre-treatment simulation CT and weekly 4D-CTs obtained from 7 patients
treated with photon radiotherapy. Planned dose distributions were deformed/mapped to each of the weekly CTs using
deformable image registration. A series of CT image features were extracted in 5Gy intervals of planned dose (5-10Gy,
10-15Gy, etc.). Features included measures of density and texture (based on gray level co-occurrence matrix and gray level
run length matrix). Paired Wilcoxon signed rank test determined significance between a feature at a given dose interval and
time point. The correlation of extracted feature between time points was assessed using the Spearman rank correlation.
Results
A selected feature from each of the three categories is plotted as a function of dose and time in Figures 1a-3a. There was no
statistically significant difference in any of the selected features between the simulation and weeks 1-5 CT datasets, though
qualitative differences were seen as early as week 2. In relation to features extracted from simulation CT, there was a
significant difference compared to week 6 over multiple levels of dose (p values shown in Figures 1b-3b). Measured
feature at simulation is plotted as a function of the measured value at week 6 in Figures 1c-3c. The Spearman rank
correlation for each of the presented features was R = 0.80, 0.76, 0.73, for mean, sum of squares variance, and long run
emphasis, respectively.
Conclusion
Lung texture/density measures change in response to radiation over time and as a function of delivered dose. The high
degree of correlation between features at simulation and features during week 6 of treatment indicate potential to predict
changes in lung texture/density based on CT scans collected before or during therapy. Ongoing analyses are being
performed to correlate these findings to clinical toxicity outcome. Quantifying changes in the lung in response to radiation
can aid in minimizing the degree of resulting lung injury and lead to further personalizing radiotherapy treatment for
individual patients.
Financial Disclosure (Shane Krafft)
No
FDA Disclosure
Cleared:Yes
Keywords
Radiation induced lung injury
Quantitative imaging
Texture analysis
None
Abstract ID: 45
Engineering of a human L-Asparagine-degrading enzyme for cancer treatment by systemic depletion
Author List
1. Presenting Author: Giulia Agnello
2. Additional Author: Everett Stone
3. Additional Author: Jason Cantor
4. Additional Author: Yan Zhang
5. Additional Author: Wenzong Li
6. Additional Author: Tae Hyeon Yoo
7. Additional Author: George Georgiou
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Acute lymphoblastic leukemia (ALL) cells, about 20% of ovarian carcinomas, certain adult non-Hodgkin lymphomas and
pancreatic carcinomas are auxotrophic for L-Asparagine (L-Asn) and therefore rely on the uptake of this amino acid from
serum for cellular proliferation. Under conditions of L-Asn starvation the auxotrophic cancer cells undergo cell cycle arrest
and apoptosis, whereas non-malignant cells that can synthesize L-Asn are unaffected. Systemic depletion of L-Asn via the
administration of L-Asparaginase (ASpase) is a potent chemotherapeutic approach for the treatment of L-Asn auxotrophic
cancers. The PEGylated E.coli Aspase has been developed for therapeutic purposes and is in clinical use under the trade
name OncosparÂ®. OncosparÂ® has been reported to be very effective in the treatment of childhood ALL; however,
consisting of a bacterial enzyme, it elicits adverse immune responses that impede its use in the treatment of a variety of
patients affected by L-Asn auxotrophic cancers. Human proteins are much less immunogenic than their heterologous
counterparts as natural tolerance is likely to prevent recognition by the adaptive immune system. We previously reported
the bacterial expression and enzymatic characterization of the human asparaginase-like protein 1 (hASRGL1), a
mammalian enzyme exhibiting beta-aspartyl peptidase activity as well as ASpase activity.
Methods
We have been using combinatorial mutagenesis approaches that, coupled to a high throughput screening, aim at optimizing
the catalytic and pharmacological properties of hASRGL1 for chemotherapy by L-Asn depletion.
Results
We recently reported the engineering of a circularly permuted form of the enzyme hASRGL1 (cp-hASRGL1). The circular
permutation decoupled the enzyme auto-processing from substrate hydrolysis, circumventing the incomplete processing of
the wild type enzyme and allowing the kinetic and structural characterization. The determination of the apo- and product
bound cp-hASRGL1 structures provide new insights for the combinatorial mutagenesis aimed at increasing the L-Asn
hydrolytic activity.
Conclusion
The engineering of the cpASRGL1 is the first step towards the development of a fully human, non-immunogenic ASpase
with the requisite catalytic activity and pharmacological properties for the treatment of L-Asn auxotrophic cancers by
systemic L-Asn depletion.
Financial Disclosure (Giulia Agnello)
No
FDA Disclosure
Cleared:Yes
Keywords
Human non-immunogenic Asparaginase
Systemic depletion
Auxotrophic cancers
Acute lymphoblastic leukemia
Abstract ID: 46
Characterizing CTCs In Breast Cancer Brain Metastasis
Author List
1. Additional Author: Lixin Zhang
2. Additional Author: Lon Ridgway
3. Additional Author: Michael Wetzel
4. Additional Author: Jason Ngo
5. Additional Author: Jerry Goodman
6. Additional Author: Wendy Schober
7. Additional Author: Morris Groves
8. Presenting Author: Dario Marchetti
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Mechanisms of fatal brain metastatic breast cancer (BMBC) are largely unknown. Similarly, properties and biomarker
identification of circulating tumor cells (CTCs), the "seeds" of metastasis, remain elusive. Here we report novel strategies
investigating CTCs isolated from peripheral blood mononuclear cells of patients with BMBC, including the development
and characterization of CTC lines.
Methods
We isolated subsets of CTCs from patients with BMBC by combining technologies alternative to CellSearchTM, such as
FICTION (BioViewTM) which allows the determination of gene amplification by FISH coupled with protein detection by
IF within the same slide and cells; along with multiparametric flow cytometry, and a highly sensitive RT-PCR employing
a thermodynamically-matched primer design to evaluate wild-type and variant gene expression.
Results
We have made four key discoveries shedding new light on the biology of CTCs, and have discovered CTC biomarkers to
predict and guide treatment of BMBC in the clinic. We identified a unique marker set investigating CTCs that could not be
captured by the Federal Drug Administration-approved Veridex CellSearchTM platform (EpCAM - negative CTCs). CTC
biomarkers included human epidermal growth factor receptor1 and 2 (EGFR and HER2), Notch1 and heparanase (HPSE)
which are high-risk predictors of BMBC onset (the CTC signature). Second, we isolated subsets of CTCs from patients
with BMBC by combining technologies alternative to CellSearchTM; along with multiparameter flow cytometry and a
highly sensitive RT-PCR employing a thermodynamically-matched primer design to evaluate wild-type and variant gene
expression. Third, we established CTC lines and analyzed their invasive and metastatic competency. EpCAM-negative
CTCs over-expressing the CTC signature were highly invasive and capable to form brain metastasis in xenografts. Tumor
cell morphologies of CTC - induced metastases closely resembled those of pathologically assessed tumors of patients
whose blood was source of isolated CTCs. Lastly, the expression of proteins of the CTC signature was detected in CTC induced xenografts BMBC.
Conclusion
Collectively, we provide first-time evidence of human CTCs isolation and long-term growth, the establishment of CTC
lines, and CTC metastatic competency in the presence of a biomarker signature necessary to promote BMBC. This study is
relevant to improve mechanistic understandings and key biomarkers driving BMBC. Strategies and results can be of
significance to develop new therapeutics for breast cancer metastasis in general, BMBC in particular.
Financial Disclosure (Dario Marchetti)
No
FDA Disclosure
Cleared:Yes
Keywords
Brain metastasis
Breast cancer
Circulating Tumor Cells
The CTC Signature
Abstract ID: 47
Isolation Of Natural Products From Marine Actinomycetes And Their Selective Therapeutic Properties
Author List
1. Presenting Author: Yazmin Carrasco
2. Additional Author: Malia Potts
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Over the course of the last 10 years, marine actinomycetes have become the frontier of natural products chemistry yielding
a large number of biologically important compounds. The MacMillan lab has developed new techniques to isolate >400
unique species of marine actinomycetes from marine sediments.
Methods
My research efforts have focused on using a library of natural product fractions created from these bacterial strains to
screen for molecules that exhibit selective cytotoxicity against a panel of tumor derived cell lines that include lung, colon,
melanoma, pancreatic cancer and glioblastoma.
Results
Screening of ~1200 fractions has resulted in a variety of active fractions that display unique activity profiles. A thorough
analysis of the activity profiles has revealed >20 fractions that exhibit selective cytotoxicity, while a large number of
fractions (>150) showed broad spectrum cytotoxicity. One of the most selective fractions exhibited an IC50=13.2 ng/mL
against the glioblastoma cell line T98G, while 10-100 times less potent against other lines. In parallel to structure
elucidation efforts of our active metabolite (SNB-003-6-6-5), the determination of its mode of action was ongoing in the
White laboratory. Through the use of a new screening tool, called FUSION (Functional Similarity Ontology) we
determined that SNB-003-6-6-5 had similar activity to inhibitors of the TBK1 signaling pathway. This led us to directly
measure the ability of the compound to inhibit AKT, GSK3b and TSC2 phosphorylation. We have screened the active
fraction and pure compound in both in vivo and in vitro TBK1 phosphorylation assays. The results indicated that
SNB-003-6-6-5 has low nM IC50 against TBK1 kinase activity. In addition, SNB-003-6-6-5 has more selectivity towards
TBK1 when compared to PDK1 and AKT.
Conclusion
We have used a combination of chemical and biochemical techniques to determine the chemistry and biology of this and
other natural products.
Financial Disclosure (Yazmin Carrasco)
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 48
Ensuring Person-centered Care: Implementing Routine Psychosocial Distress Screening Within An Ambulatory
Community Cancer Center
Author List
1. Presenting Author: Joni Watson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Evidence-based prevention services: primary, early detection, survivorship
Uploaded Files
none
Summary
Introduction
The Commission on Cancer (CoC) Standard 3.2, Psychosocial Distress Screening, will be phased into national, accredited
cancer care during 2015. The standard ensures â€œon-site psychosocial distress screening and referral for the provision of
psychosocial careâ€• in accordance with the Institute of Medicineâ€™s 2007 landmark report Cancer Care for the Whole
Patient: Meeting Psychosocial Health Needs. Cancer-related distress may arise from physical, emotional, spiritual, or
practical concerns, and it can impact treatment plans, quality of life, and patient outcomes. Psychosocial distress must be
assessed and addressed in order to provide quality, person-centered care.
This presentation discusses Seton Healthcare Familyâ€™s successful efforts to implement routine psychosocial distress
screening within Shivers Cancer Center, an ambulatory community cancer center providing care to uninsured and
underinsured cancer patients within an 11-county Central Texas region.
Methods
Utilizing the National Comprehensive Cancer Networkâ€™s Distress Thermometer - a standardized, validated, one-page
visual-analog scale and patient-generated problem list - the Cancer Care Team (CCT), which provides supportive care
services to Shivers Cancer Center patients, developed a pilot process for the new distress screening practice; translated the
screening tool into Spanish; secured care pathways to include patient navigation and other services based upon mild,
moderate, or severe distress scoring; educated staff of the tool and pathways; and created a full-implementation timeline to
include revisions of the forms and process flow as a result of the pilot results.
Results
The pilot screening process lasted two weeks. The CCT learned many valuable lessons to improve routine distress
screening in our ambulatory setting. In addition, we were able to assess anticipated health-literacy issues as a potential
barrier to completing the patient-generated tool and evaluate the amount of time health professionals spent with patients
conducting the screening and coordinating referrals based on the scoring criteria. The CCT took the lessons learned, made
adjustments, and began routinely assessing all new cancer patients within Shivers Cancer Center of psychosocial distress in
January 2012.
Conclusion
Setonâ€™s psychosocial distress screening process and care pathways leverage existing organizational and community
resources to provide holistic cancer care to a disparate and vulnerable population. The process and pathways continue to
evolve within the Seton Healthcare Family and Central Texas community as new policies are developed and additional
resources are identified, providing a new depth of psychosocial cancer care. Setonâ€™s model has been shared with other
community cancer centers and is replicable by other organizations to ensure person-centered care.
Financial Disclosure (Joni Watson)
No
FDA Disclosure
Cleared:Yes
Keywords
psychosocial
distress
CoC Guidelines
person-centered care
Abstract ID: 49
Continuous-wave Radar Sensor For Accurate Respiration Pattern Monitoring In Motion-adaptive Cancer
Radiotherapy
Author List
1. Additional Author: Changzhan Gu
2. Presenting Author: Changzhi Li
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
setup.jpg
Summary
Introduction
Cancer is the second leading cause of death in US. Radiotherapy is a major modality for treating cancer patients. However,
in many anatomic sites, e.g. lung and liver, the tumor is subject to motion caused by respiration. Accurate respiration
measurement is of vital importance in motion-adaptive cancer radiotherapy. However, the conventional respiration
measurement techniques either need close patient contact to the device or do not have efficient accuracy. Continuous-wave
radar sensor has been proposed by the researchers for noncontact respiration measurement. However, the respiration
motion has such a low frequency (< 0.5 Hz) that the conventional AC coupled radar sensor leads to significant signal
distortion, which makes it challenging for effective motion adaptive radiotherapies that strictly rely on accurate respiration
signals. Tumor tracking is a promising motion-adaptive radiotherapy. It requires simultaneous measurement of the
respiration motions at chest and abdomen. However, it suffers from the limited space available in the LINAC to house two
radar sensors.
Methods
In this paper, a DC coupled continuous-wave radar sensor with beam-scanning capability is presented for accurate
simultaneous measurement of the respiration motions at chest and abdomen. Unlike the conventional AC coupled radar
sensor, the proposed DC coupled structure allows all the respiration information to be accurately detected, including the
short stationary moment at the end of expiration. The radar sensor was integrated with a beam-scanning antenna that is able
to sweep the radiation beam within a predefined angle by electronically controlling the phases of the feed-in signals. The
beam-scanning antenna can sweep very quickly (1 <Âµs). In this way, one radar sensor is enough to simultaneously
measure the respiration motions at the chest and abdomen, which resolve the problem of space constraint.
Results
This paper would report our recent experiments using the DC coupled radar sensor to accurately measure respiration
motions. Comparison will be discussed by comparing with the conventional AC coupled radar sensor. The capability of the
beam-scanning antenna would be experimentally tested in the lab environment. It is shown that the proposed DC coupled
radar sensor with beam-scanning capability can simultaneously measure the respiration at two locations and preserve the
signal integrity of the respiratory motion.
Conclusion
It will be shown that the proposed DC coupled radar sensor with beam-scanning capability can reliably measure respiratory
motion for both gated radiotherapy and accurate tumor tracking. Further development and potential collaboration
opportunities will also be discussed.
Financial Disclosure (Changzhi Li)
No
FDA Disclosure
Cleared:Yes
Keywords
radar
respiration measurement
cancer radiotherapy
motion-adaptive
Abstract ID: 50
The Rural Texas Physician Cancer Screening Education Program In High-risk Cancer Cluster Regions
Author List
1. Additional Author: Elizabeth Balyakina
2. Additional Author: Ana Luz Chiapa-Scifres
3. Additional Author: Kimberly Fulda
4. Additional Author: Anna Espinoza
5. Additional Author: John Bowling
6. Additional Author: Keith Argenbright
7. Presenting Author: Roberto Cardarelli
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Public and health professional education and training
Uploaded Files
none
Summary
N/A
Introduction
While cancer rates in rural and urban areas are similar, those living in rural Texas are found with more advanced cancer at
the time of diagnosis. Therefore, it is critical for rural physicians to be up-to-date with the most recent knowledge about
cancer screening guidelines and be prepared to offer prevention to patients at every opportunity. To address these needs,
this project aimed to (1) distribute a developed educational evidence-based DVD on cancer screening guidelines to rural
physicians practicing in cluster regions with high cancer rates in Texas, and (2) impact cancer screening behavior of
physicians in the proposed rural Texas regions by providing the educational DVD on cancer screening guidelines.
Methods
A developed 1-hour DVD with evidence-based lectures on seven cancer screening guidelines delivered by respected Texas
specialists was mailed to 2458 rural physicians practicing in high-risk cancer cluster regions in Texas. The seven lectures
include cancer screening guidelines for the following cancers: breast, colorectal, lung, skin, cervical and ovarian, and
prostate. The 78 Texas counties included in the mail-out are Health Professional Shortage Areas (HPSAs) in high-risk
cluster areas for one of the cancers that are lectured in the DVD. The evaluation component of the program utilizes 12 rural
clinics that are affiliated with the Rural Osteopathic Medical Education (ROME) program at the UNT Health Science
Center at Fort Worth to assess changes in knowledge, attitudes, and practices of physicians using a developed pre-post
questionnaire and 750 medical chart reviews.
Results
Of the 2458 DVDs that were sent out in May 2011, 2405 DVDs were delivered to physicians practicing in high-risk cancer
cluster regions in Texas. Thirteen physicians completed the consent process and the pre- and post-test portion of the study.
Analysis of the pre-post surveys indicate a change in skin cancer screening (p=0.007) and ovarian cancer screening beliefs
(p=0.03).
Conclusion
The program offers to bring evidence-based education using a DVD format to rural physicians specifically practicing in
high-risk cancer cluster regions in Texas. This extends to 78 counties in Texas and approximately 2,500 physicians, thus
impacting the populations they serve. Chart reviews are currently in progress to evaluate physician cancer screening
practices and intermediate study outcomes.
Financial Disclosure (Roberto Cardarelli)
No
FDA Disclosure
Cleared:Yes
Keywords
Cancer screening
Continuing medical education
High-risk cancer cluster regions
Rural medicine
Abstract ID: 51
Geographic Variation Of Medical Discrimination And Cancer Testing In The United States
Author List
1. Presenting Author: Roberto Cardarelli
2. Additional Author: Kristen Hahn
3. Additional Author: Vishwam Pandya
4. Additional Author: Elizabeth Balyakina
5. Additional Author: Kendra Malone
6. Additional Author: Kathryn Cardarelli
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Experiencing discrimination in a healthcare setting can have a harmful impact on utilization of medical services and
general health, resulting in delayed medical care and prescription refills, lower rates of cancer screening and other
preventive screening tests, loss of trust in medical providers, decreased adherence to medical recommendations, and less
definitive recommendations from providers. The goal of this study was to examine the impact of discrimination in
healthcare settings on cancer screening behaviors for colorectal, breast, cervical, and prostate cancer by region of the
United States. We posited that higher rates of medical discrimination in the Southern United States would be associated
with an increased odds of inadequate cancer screening in that region as compared to other parts of the United States.
Methods
The geographic regions examined in this study were â€œSouthâ€•â€™ and â€œOther.â€• Responses of non-Hispanic
African American and non-Hispanic white participants from the 2004 Behavioral Risk Factor Surveillance System
Reactions to Race module were utilized in the analysis. Adequacy of cancer testing and exposure to discrimination in a
medical setting were examined separately by cancer type and region. Simple and multiple logistic regression were
performed to determine the association between adequacy of cancer testing and perceived racial or ethnic-based medical
discrimination. Multivariate results were further stratified by race for colorectal cancer testing in the South region due to
the modifying effect of race on the relationship between medical discrimination and colorectal cancer testing.
Results
Multivariate analysis showed that after adjustment for covariates, experiencing discrimination in a medical setting was only
significantly associated with higher odds of inadequate colorectal cancer testing in the South region among whites. Results
approached significance for cervical and prostate cancer in the South.
Conclusion
Although the present study only indicated a strong association between perceived medical discrimination and adequacy of
colorectal cancer testing among non-Hispanic whites in the South region, underlying geographic patterns related to cancer
testing and discrimination may become apparent with a larger sample size or with the addition of other geographic regions.
Studies utilizing individual-level data and Geographic Information Science would be able to more accurately describe the
underlying phenomena.
Financial Disclosure (Roberto Cardarelli)
No
FDA Disclosure
Cleared:Yes
Keywords
Medical geography
Early detection of cancer
Social discrimination
None
Abstract ID: 52
Identification Of Binding Partners And Pathway Identification For Novel DNA Repair Proteins
Author List
1. Additional Author: Kei-ichi Takata
2. Additional Author: Junya Tomida
3. Additional Author: Shelley Reh
4. Additional Author: Chia Fang Lee
5. Additional Author: Marvin Mercado
6. Additional Author: Yueping Chen
7. Additional Author: Jianjun Shen
8. Additional Author: Richard Wood
9. Presenting Author: Maria Person
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Over 175 proteins contribute directly to repair of DNA damage in human cells and for some of them little is known of their
precise functions. One approach to clarify function is to discover protein partners, revealing the relevant cellular pathways
in which a protein acts. Recent improvements in the sensitivity of ion trap mass spectrometers enable identification of low
abundance proteins and modification analysis. We are identifying partners of novel DNA repair proteins by mass
spectrometry of gently isolated protein complexes. 
Methods
A retroviral vector is used to obtain HeLa cells stably expressing an epitope-tagged protein as “bait”, usually
with FLAG and HA epitope tags. A cell free protein extract is prepared from the culture of an expressing HeLa cell clone
and sequentially immunoprecipitated with anti-FLAG and anti-HA antibodies. Proteins are then separated on
polyacrylamide gels and analyzed by silver and Sypro-Ruby staining. Proteins from gel sections are identified using LTQ
Velos Pro and Orbitrap Elite mass spectrometry instrumentation. The SEQUEST search in the Proteome Discoverer
software is used for protein identification, followed by validation using the Scaffold program. Results are filtered for
peptide and protein confidence, and known background proteins (recurrent hits obtained with unrelated bait proteins in the
same or similar system). Protein identifications are checked for agreement with the molecular mass predicted from the
relevant gel slice. Post-translational modifications are identified via the PhosphoRS and Scaffold PTM programs.
Results
As an example, HELQ is a DNA helicase initially cloned in the Wood laboratory by homology with the DNA polymerase
POLQ. The cellular function of HELQ is unclear. Using HELQ as bait, we identified the RAD51B, RAD51C, RAD51D
and XRCC2 proteins as binding partners. The latter four proteins are known as the "BCDX2" complex, a group of
RAD51-related proteins with functions in homologous recombination. The DNA damage-responsive kinase ATR and its
partner ATRIP were also identified as binding partners. In contrast, interaction of HELQ with the DNA polymerase POLN,
proposed by others as an interacting partner, was not verified. All results were confirmed by immunoblotting.
Phosphorylation and ubiquitination sites were also identified on HELQ. We constructed a knockout of HELQ in a human
cell line using zinc finger technology. Like RAD51 paralogs, HELQ knockout cell lines showed sensitivity to
DNA-crosslinking agents including MMC and cisplatin.
Conclusion
These experiments suggest that HELQ operates in a pathway of DNA recombinational repair and as part of a
“checkpoint” response to damaged DNA.
Financial Disclosure (Maria Person)
No
FDA Disclosure
Cleared:Yes
Keywords
mass spectrometry
protein identification
DNA repair
HELQ
Abstract ID: 54
Content Analysis of Online Social Networks suggests Strategies for Personalizing Smoking Cessation Support
Systems
Author List
1. Presenting Author: Sahiti Myneni
2. Additional Author: Nathan Cobb
3. Additional Author: Trevor Cohen
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Figure 1- Network visualization of QuitNet Communication Themes.jpg
Summary
Introduction
Ubiquitous virtual social networks provide us with a unique opportunity to deliver scalable interventions for supporting
lifestyle modifications in order to change behaviors that predispose toward cancer. At the same time these networks act as
rich data sources to understand end-user needs and motivation. Traditionally, social network analysis is conducted based on
communication frequency among members. In this work, we introduce communication content as a complementary frame
for studying these networks.
Methods
QuitNet, an online social network developed to provide smoking cessation support was considered for analysis. A total of
16,475 messages were analyzed using qualitative coding, automated content mining, and network analysis to construct
QuitNet sub-networks based on both frequency and content of communication. This merging of qualitative, quantitative,
and automated methods enabled us to characterize the nature of communication among network members, thereby
expanding the breadth and depth of the existing network analysis techniques. The grounded-theory based qualitative
analysis provided a microscopic view of the QuitNet message themes. Using automated text analysis, links between
network members were derived based on the relatedness of the content in the exchanged messages to exemplar terms
pertinent to each of the identified themes. Such automated analysis allowed us to expand the labor-intensive qualitative
methods to a large data sample using minimal time and resources. By modifying methods of network analysis to
accommodate the content of communication, we were also able to characterize content-specific networks of
communication within QuitNet.
Results
Content analysis of QuitNet messages identified themes ranging from reinforcement, social support, stories of personal
experience to cravings, Nicotine Replacement Therapy, and reasons for relapse. Preliminary visualization allowed us to
model content-specific sub-networks for each theme separately. We also found that different theme-based networks had
different opinion leaders and each theme had more than one opinion leader, observations that were not apparent when the
network was derived from communication frequency data alone. In the â€œreinforcementâ€• sub-network, all the opinion
leaders were clustered forming a community of their own, while in â€œsupportâ€• sub-network the leaders were dispersed.
Conclusion
This study provides insights into the nature of communication among members in a smoking cessation virtual network. The
ability to identify critical nodes and content-specific network patterns has implications for the development and
maintenance of support networksto promote positive health behavior changes. Modeling health-related social network data
using both frequency and content can allow us to generate ecologically-valid, tailored, and targeted behavioral
interventions.
Financial Disclosure (Sahiti Myneni)
No
FDA Disclosure
Cleared:Yes
Keywords
smoking cessation
content analysis
social network
behavior change
Abstract ID: 55
Next Generation Sequencing And Chromosomal Microarray Analysis Provide Novel Insight Into The Genomic
Landscape Of Metastatic Breast Cancer
Author List
1. Presenting Author: Condie Carmack
2. Additional Author: Marilyn Li
3. Additional Author: Yu-Ye Wen
4. Additional Author: Phillip Chen
5. Additional Author: Erica Fang
6. Additional Author: Yanchun Li
7. Additional Author: Ganka Douglas
8. Additional Author: C. Kent Osborne
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Although most breast cancer cases are curable nowadays, approximately 25% of breast cancer patients develop metastatic
disease and eventually die of breast cancer. To understand the mechanism of tumor metastasis and identify potential
prognostic and therapeutic biomarkers, we studied 10 metastatic breast cancer tumors with paired blood samples using
Next Generation Sequencing (NGS) (CMA) and Chromosomal Microarray Analysis technologies.
Methods
The NGS mutation panel interrogates 739 common mutations in 46 key cancer genes including many clinically actionable
mutations using a technology that merges multiplex PCR with ion semiconductor sequencing. The arrays used in the study
are custom-designed CGH+SNP arrays that target approximately 2,300 cancer genes or cancer-associated genes with an
average of 6 probes per exon.
Results
NGS identified 10 mutations in 7 tumor samples including mutations in TP53, PIK3CA, APC, ATM, MET, NRAS, and
EGFR. CMA showed genomic aberrations in all tumor samples. The most common genomic alterations were 1q
duplication or amplification observed in 9 of 10 cases followed by 8q duplication/amplification, part or full chromosome 5
duplication, and 17p deletion. Other common aberrations were 20q duplication/amplification, 9p deletion, and different
alterations of chromosome 16. TP53 mutations appear to be associated with complex genomic alterations involving many
chromosomes, especially 8q duplication/amplification, 7p deletion, and 20q duplication/amplification, and poor prognosis.
Conclusion
Studies of primary tumor and tumor samples before and after treatment showed similar genomic alteration patterns,
suggesting that the genomic alterations identified in primary tumors could be used to predict tumor metastasis and choose
appropriate treatment regimens. In addition, mutations identified may help in selecting an effective targeted therapy.
Financial Disclosure (Condie Carmack)
Have a financial arrangement or affiliation with commercial companies whose products may be mentioned in this
material? Yes
Paid consultant or employee: Yes
- Science Advisory Board
FDA Disclosure
Cleared:Yes
Keywords
next-generation sequencing
chromosomal microarray analysis
mutational analysis
targeted therapy
Abstract ID: 56
Introducing New Effector Function To IgG By Engineering Affinity For The IgAFcÎ±RI Receptor
Author List
1. Presenting Author: William Kelton
2. Additional Author: Nishant Mehta
3. Additional Author: Oana Lungu
4. Additional Author: Takaaki Kojima
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
All of the current antibody therapeutics approved for clinical use are derived from the IgG isotype. A key contributor to the
therapeutic effect mediated by these antibodies is the activation of the human immune system through the engagement of
FcÎ³Rs on innate effector cells. Upon activation, potent ADCC and ADCP responses neutralize a wide variety of targets
including cancer cells, bacteria and inflammatory proteins. However, it may be possible to improve therapeutic response by
engaging additional Fc receptors that typically bind the other antibody isotypes. We have engineered an IgG domain with
affinity for FcÎ±RI, a receptor that typically binds exclusively to IgA. FcÎ±RI is strongly activated by immune complexes
and constitutively expressed on many myeloid cells with potent ADCC function such as neutrophils. By introducing
FcÎ±RI binding to an IgG, several complications that would arise during production of an IgA therapeutic are circumvented
including low expression yields and challenging purification regimes encountered during recombinant production. Our
antibody variant retains binding to the activating FcÎ³Rs so that synergistic activation can occur with FcÎ±RI.
Methods
We have used a combination of rational design, computer aided design using the Rosetta software suite and the screening
of large libraries of Fc variants by FACS to generate our antibody variants. Affinity characterization by ELISA and
Biacore has been used to select variants with high receptor binding for evaluation by in vitro ADCC assays.
Results
We have isolated Fc variants that retain high binding affinity for the activating Fc receptors (FcÎ³RI, FcÎ³RIIa and
FcÎ³RIIIa) and have new binding for FcÎ±RI introduced. Interestingly there is a reduced affinity for the inhibitory receptor
FcÎ³RIIb.
Conclusion
By selectively engaging certain Fc receptors on immune cells we hope our antibody variants will be useful for treating a
wide range of human ailments including cancers.
Financial Disclosure (William Kelton)
No
FDA Disclosure
Cleared:Yes
Keywords
Protein engineering
Antibody engineering
Bacterial display
Directed evolution,
Abstract ID: 57
Dissociation Of ATP-binding Cassette Nucleotide-Binding Domain Dimers Into Monomers During The Hydrolysis
Cycle
Author List
1. Additional Author: Maria Zoghbi
2. Additional Author: Srinivasan Krishnan
3. Presenting Author: Guillermo Altenberg
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Altenberg-Associated file.JPG
Summary
N/A
Introduction
ATP-binding cassette (ABC) proteins catalyze the transport of substrates across membranes. Many ABC proteins,
including P-glycoprotein, pump substrates out of the cells. There are two competing models to explain the mechanism of
ABC exporters: 1) The alternating-access model, where large conformational changes take place during the transport cycle
as a consequence of ATP-induced nucleotide-binding domain (NBD) dimerization. 2) An alternative model, which
suggests that the power stroke triggered by ATP binding consists of only moderate rearrangements, with the NBDs in
contact at all times during the transport cycle.
Methods
We performed experiments on isolated bacterial NBDs using luminescence resonance energy transfer (LRET) and
tryptophan fluorescence spectroscopy, to assess monomer association/dissociation in real time. We used MJ0976, a NBD
from the thermophile M. jannaschii, as a model.
Results
NBD dimerization can be monitored by both, Trp174 fluorescence and LRET. In the absence of Mg, ATP slowly induces a
stable dimerization of the NBDs, which can be observed as 1) quenching of Trp174 fluorescence due to the pi-stacking of
the Trps, and 2) an increase in LRET signal due to the increased proximity of donor- and acceptor-labeled monomers.
Addition of Mg promotes hydrolysis of ATP by the dimers and reverses 50-60% of the ATP-induced Trp quenching and
LRET signal. Lifetime measurements with calculations of the donor-acceptor LRET distances indicate that the
donor-acceptor distances remained unchanged in the dimers during the ATP hydrolysis cycle.
Conclusion
We conclude that : 1) The dependence of dimerization for MgATP is stronger (Kd of ~ 5 micromolar) than that for NaATP
(~80 micromolar). 2) The rate of dimerization increased >10-fold in MgATP vs. NaATP. 3) A steady-state dynamic
equilibrium is reached in MgATP, with ~50% of the protein in dimeric form. 4) The dimers completely dissociate into
monomers during the hydrolysis cycle. Our LRET distance calculations strongly favor the first scenario, and therefore
support the ABC NBD hydrolysis models that include association/dissociation, as opposed to constant-contact models.
Financial Disclosure (Guillermo Altenberg)
No
FDA Disclosure
Cleared:Yes
Keywords
ABC protein
multidrug resistance
spectroscopy
energy transfer
Abstract ID: 59
A Human Virus Oncoprotein Activates PI3K By Tethering The p85-p110 Heterocomplex To Dlg1 At The Plasma
Membrane
Author List
1. Presenting Author: Kathleen Kong
2. Additional Author: Manish Kumar
3. Additional Author: Midori Taruishi
4. Additional Author: Ronald Javier
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Kong CPRIT data.jpg
Summary
Introduction
Tumor viruses are powerful tools for revealing mechanisms of cancer. In infected experimental animals, human adenovirus
type 9 generates estrogen-dependent mammary tumors. The tumorigenic potential of this virus depends on the
virus-encoded E4-ORF1 oncoprotein and its ability to activate cellular phosphatidylinositol 3-kinase (PI3K). It is not
known how E4-ORF1 activates PI3K, though previous findings show that this crucial activity requires an interaction
between E4-ORF1 and the cellular protein Dlg1, as well as translocation of the complex to the plasma membrane. The goal
of the current study was to determine the mechanism for E4-ORF1-induced PI3K activation.
Methods
Human MCF10A mammary epithelial cells expressing a wild-type or mutant E4-ORF1 protein were generated using
retroviral vectors. Oncogenic cellular transformation was measured in focus formation and soft agar assays.
Immunoprecipitation/GST pulldown, western blot, and immunofluorescence assays were used to detect protein complexes,
levels, and subcellular localization, respectively. An shRNA approach was used to knockdown protein expression.
Results
Mass spectrometry analysis of cellular proteins that associate with a GST-E4-ORF1 fusion protein identified the p85
regulatory and p110 catalytic subunits of PI3K as candidate binding partners. Immunoprecipitation (IP) assays confirmed
that these interactions occur in cells. Specifically, (i) E4-ORF1 was recovered after IP of either p85 or p110 and (ii) p85,
p110, and E4-ORF1 were recovered after IP of Dlg1. Results with cells expressing either an E4-ORF1 mutant unable to
bind Dlg1 or a Dlg1 shRNA indicated that E4-ORF1 binds to PI3K independently of Dlg1. Western blot analyses
additionally showed that E4-ORF1 elevates p85 and p110 protein levels in cells, and immunofluorescence assays revealed
PI3K activation at the plasma membrane where PI3K/E4-ORF1/Dlg1 complexes accumulated. Linking these findings to
oncogenic transformation, focus formation and soft agar growth of E4-ORF1-expressing MCF10A cells were abolished by
treatment with a PI3K inhibitor or by E4-ORF1 mutations that reduce or eliminate binding to PI3K or Dlg1.
Conclusion
This study revealed a novel mechanism for oncogenic PI3K activation. Specifically, our findings support a model wherein
E4-ORF1 uses separate domains to bind PI3K and Dlg1 and, in so doing, tethers these cellular factors into a single
complex that potently activates PI3K at the plasma membrane. Given the high frequency of PI3K pathway dysregulation in
human cancers, studies of this viral-cellular protein complex may provide new insights into PI3K regulation in normal cells
and dysregulation in cancer cells. This information may lead to the development of new therapeutic drugs capable of
treating and preventing many human cancers.
Financial Disclosure (Kathleen Kong)
No
FDA Disclosure
Cleared:Yes
Keywords
Virus
Oncoprotein
Dlg1
PI3K
Abstract ID: 60
Developing Putative Inhibitors Of Uroporphyrinogen Decarboxylase : Towards Novel Radiosensitizers
Author List
1. Presenting Author: Zhan Zhang
2. Additional Author: Kenneth Yip
3. Additional Author: Jonathan Sessler
4. Additional Author: Fei-Fei Liu
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Uroporphyrinogen decarboxylase (UROD) is the fifth enzyme of the heme biosynthetic pathway. Previous studies have
served to show that inhibiting heme biosynthesis by UROD knockdown promotes radiation-induced apoptosis.Thus UROD
has been suggested as a radiosensitizing target for head and neck cancer. In separate studies, it was found that
uroporphomethenes, a partially oxidized uroporphyrinogen, can inhibit the activity of UROD. However, such compounds
are chemically unstable in the the presence of oxygen.
Methods
In the current study, a series of linear pyrrolic compounds and porphomethenes have been developed as putative inhibitors
of UROD. We carried out the enzymatic assay using both UROD and the upstream porphobilinogen deaminase (PBGD).
Various products were detected using RP-HPLC/450 nm absorbance. FaDu cells were seeded for cell viability assay which
was measured using ATPLite (PerkinElmer). Clonogenic assay was performed using FaDu cells as well. After the cells
were seeded and later treated with the synthetic compounds, they were exposed to ionizing radiation. Cells were fixed and
stained and colonies were counted.
Results
Our preliminary studies show that one of the synthetic compounds displayed good selectivity toward UROD and did not
affect the activity of the upstream PBGD. In vitro tests provided support for the predicative hypothesis associated with this
project, namely that the surviving chance of the carcinoma cells upon radiation can be reduced in the presence of the
putative inhibitors.
Conclusion
Based upon the observations, synthetic porphomethenes can work as novel, promising radiosensitizers by inhibiting
UROD, albeit the potency observed so far needs to be improved through structural modification of these putative
inhibitors.
Financial Disclosure (Zhan Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 61
The Total Synthesis Of Actinophyllic Acid
Author List
1. Presenting Author: Brett Granger
2. Additional Author: Ivan Jewett
3. Additional Author: Jeffrey Butler
4. Additional Author: Bruce Hua
5. Additional Author: Claire Knezevic
6. Additional Author: Paul Hergenrother
7. Additional Author: Stephen Martin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Capture.JPG
Summary
N/A
Introduction
Actinophyllic acid is a complex indole alkaloid isolated in 2004 by Carroll and co-workers from the leaves of Alstonia
actinophylla, a tree native to the Cape York Peninsula, Queensland, Australia. It was isolated via bioassay-guided
fractionation utilizing an activated thrombin-activatable fibrinolysis inhibitor (TAFIa)/hippuricase coupled enzyme assay,
and is a potent inhibitor of this two-step enzymatic process (IC50 = 0.84 ÂµM).In addition to its pertinent role in
regulating fibrinolysis, TAFIa has also been implicated in several cancer related studies. Of particular interest, patients
with various types of lung cancer, breast cancer, and gastric cancer invariably show significantly increased levels of TAFI
in plasma relative to healthy controls. Currently, no information is available about the inhibition of TAFIa in humans with
cancer, but it is expected to contribute to the arrest of tumor growth and metastasis.
Methods
To date, there have been two publication disclosing the progress towards the synthesis of (Â±)-actinophyllic acid by the
Wood group and the Taniguchi group, as well as two separate reports on the total synthesis of (Â±)- and
(â€“)-actinophyllic acid by the Overman group. Our strategy relies on the union of two fragments through a novel
N-acyliminium ion mediated cascade reaction to provide the core of the natural product. Subsequent closure of the upper
pyrrolidine ring, and lower tetrahydrofuran ring complete the skeleton of the natural product.
Results
We have successfully developed our key N-acyliminium ion mediated cascade reaction to proceed in 92% yield, giving rise
to the formation of one ring, one quaternary carbon, and two stereocenters. Adaption of known chemistry has subsequently
allowed for synthesis of the natural product. Additionally, several advanced intermediates were shown to have potent
activity against various breast cancer cell lines, and were shown to act by interfering with mitosis. Current studies are
aimed at the interaction of these intermediates with tubulin.
Conclusion
We have developed a novel N-acyliminium ion mediated cascade reaction that has allowed for the total synthesis of
(Â±)-actinophyllic acid in an efficient manner. We are currently investigating structure-activity relationships of active
intermediates as well as the mechanism of action of these compounds. Upon completion of the synthesis it is now our hope
to probe the effects of inhibiting TAFIa in cancer patients.
Financial Disclosure (Brett Granger)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 62
Concomitant Targeting Of Tumor Cells And Induction Of T Cell Response Synergizes To Effectively Inhibit
Trastuzumab-resistant Breast Cancer
Author List
1. Additional Author: Qingfei Wang
2. Additional Author: Shau-Hsuan Li
3. Additional Author: Hai Wang
4. Additional Author: Yi Xiao
5. Additional Author: Ozgur Sahin
6. Additional Author: Samuel Brady
7. Additional Author: Ping Li
8. Additional Author: Elizabeth Jaffee
9. Additional Author: Gabriel Hortobagyi
10. Presenting Author: Dihua Yu
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Trastuzumab is an iconic example of rationally designed targeted therapy for HER2-positive breast cancers; however,
trastuzumab resistance is an imposing clinical challenge that calls for novel approaches to better benefit patients. The
purpose of this study was to find alternative combinatorial targeted therapies to overcome trastuzumab resistance.
Methods
We used two distinct PTEN-loss mediated trastuzumab resistant mammary tumor mouse models. Cytotoxic
T-lymphocyte-associated antigen 4 (CTLA-4) and Akt inhibitor triciribine (TCN) were applied alone or in combination
with 7.16.4 antibody, the mouse equivalent of the trastuzumab, for the treatment of tumor-bearing mice. Immunoblotting,
immunohistochemistry, in vivo cytotoxicity assay and quantitative real time PCR were employed to dissect the in vivo
effects of the treatments and molecular changes.
Results
Concomitant targeting of tumor cells with Akt inhibitor TCN plus trastuzumab, and activation of T cells with anti-CTLA-4
antibody in the tumor microenvironment results in a synergistic inhibitory effect on tumor growth and overcomes
trastuzumab resistance in both mammary tumor mouse models. In vivo combinatorial treatment with the 7.16.4 HER2/Neu
antibody and TCN effectively inhibited tumor growth in both models via inhibiting PI3K/AKT and MAPK signaling
accompanied by increased T cell infiltration in the tumor microenvironment. We demonstrated that both CD8+ and CD4+
T cells were essential to the optimal antitumor effect of the combination treatment in an IFN-Î³-dependent manner.
Importantly, the antitumor activities of HER2/Neu antibody and TCN combination treatment were further improved when
we blocked co-inhibitory receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to enhance the T cell response.
Conclusion
Our data indicate that multi-targeted combinatorial therapies targeting tumor cells and concomitantly enhancing T-cell
response in the tumor microenvironment cooperated to exert maximal therapeutic activity. We propose that concomitant
targeting tumor cells and tumor microenvironment is a promising clinical strategy for treating trastuzumab-resistant breast
cancers and other advanced malignancies. 
 
Financial Disclosure (Dihua Yu)
No
FDA Disclosure
Cleared:Yes
Keywords
trastuzumab resistance
Akt inhibitor
anti-CTLA4
breast cancer
Abstract ID: 63
The Role Of The Androgen Receptor In Metastasis And Hormone Resistance Of Estrogen Receptor Positive Breast
Cancer.
Author List
1. Presenting Author: Andrew Ciupek
2. Additional Author: Lauren Brusco
3. Additional Author: Kyle Covington
4. Additional Author: Nancy Weigel
5. Additional Author: Yiling Lu
7. Additional Author: Suzanne Fuqua
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
We have previously developed a novel model of breast cancer metastasis involving shRNA knockdown of Rho GDIÎ±, an
inhibitor of the GTP hydrolyzing enzymes of the Rho family. Also although it is known that androgen receptor (AR) is
frequently expressed along with estrogen receptor (ER) Î± in breast tumors, ARâ€™s role in resistance or metastasis is
unknown. Here we explore the role of AR in these processes in the Rho GDIÎ± knockdown model.
Methods
shRNA knock down was used to block expression of Rho-GDIÎ± in the ERÎ±-positive MCF-7 breast cancer cell line.
Reverse phase protein arrays (RPPA) were also used to analyze global changes in growth factor pathway expression.
Metastasis of the cells was analyzed by injection into athymic mice followed by histological analysis of isolated tissues.
Western blot analysis was used to look at activation of the AR, ER, and Rho-GTPase pathways. The effects of AR
inhibitors and agonists on anchorage independent growth, proliferation, and invasion were measured in soft agar colony
formation assays, MTT growth assays, and matrigel invasion assays respectively.
Results
The MCF-7 Rho GDIÎ± knockdown cells exhibited increased lung metastases, and were resistant to the growth inhibitory
effects of Tam when grown as xenografts in vivo. We discovered that AR was overexpressed in the Rho GDIÎ±
knockdown cells as well, as confirmed by both western blot and RPPA. Increased activation of the Rho-GTPases was seen
in knock down cells through Immunoprecipitaion assays. Increased basal levels of anchorage independent growth and
proliferation were seen in knockdown cells which could be blocked by inhibition of AR function using the antagonist
bicalutimide, known as CasodexTM. The synthetic AR agonist R1881 increased invasion of knock down cells
but not parental control cells.
Conclusion
Given our data showing that AR was significantly overexpressed with the metastatic and Tam-resistant phenotype, we
hypothesize that AR overexpression may play a role in these processes. We are focused on understanding whether the
resistance conferred by AR overxpression is pivotal for the multistep process of metastasis. Our results suggest that AR
may represent a new clinical target for hormone therapy resistance of ERÎ± positive breast cancer.
Financial Disclosure (Andrew Ciupek)
No
FDA Disclosure
Cleared:Yes
Keywords
breast cancer
androgen receptor
metastasis
endocrine resistance
Abstract ID: 64
Nurse And Social Worker Training - Access To Cancer Care For Low-income And Uninsured Patients
Author List
1. Presenting Author: Melissa Mims
2. Additional Author: Carolyn Bernard
3. Additional Author: James Cavalier
4. Additional Author: Donna Suckow
5. Additional Author: Robert Volk
6. Additional Author: Rosalind Bello
7. Additional Author: Lewis Foxhall
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Many Texas nurses and social workers work with low-income and uninsured patients, particularly those in rural and
underserved areas and areas with large Spanish-speaking populations. These populations face barriers in identifying
potential sources of preventive services and medical care. Increasing nursing and social worker knowledge of available
services and tools, such as TCIâ€™s Access to Care interactive database, and improving competencies in
using the best procedures to get patients the information they need can improve access and ultimately improve outcomes.
Methods
TCI created the Access to Cancer Care for Low-Income and Uninsured Patients online continuing education
program (CE) for nurses and social workers who facilitate connecting individuals with the care they need. The TCI CE
planning committee consisting of TCI staff, MD Anderson nurse educators and social workers, an online curriculum
specialist, a Nurse Oncology Education Program representative and the program evaluator guided the content development
for online, learner-paced CE modules. These slidecasts include slides with voiceover containing content related to six
learning objectives. A series of four case study video vignettes demonstrate the desired behaviors enabling the learner to be
more actively engaged in the educational experience. A framework was developed to deliver online CE, testing, evaluation
and certification.
Results
Within one week of the release of the CE, over 100 participants were reached. The goal of reaching 1500 nurses and 500
social workers in Texas is expected within one year. Project has further strengthened collaboration with the TCI Advisory
Committee, made up of health, education and planning professionals from a wide variety of cancer-related and
community-based agencies and fostered new, rewarding collaborative relationships with nurses and social workers.
Promotion and dissemination of the CE has been possible through partnerships with nursing and social work organizations
with emphasis on reaching those in rural, underserved areas and areas with large Spanish-speaking populations.
Conclusion
Within one week of the release over 100 participants were reached. The goal of reaching 1500 nurses and 500 social
workers in Texas is expected within one year. Project has further strengthened collaboration with the TCI Advisory
Committee, made up of health, education and planning professionals from a wide variety of cancer-related and
community-based agencies and fostered new, rewarding collaborative relationships with nurses and social workers.
Promotion and dissemination of the CE has been possible through partnerships with nursing and social work organizations
with emphasis on reaching those in rural, underserved areas and areas with large Spanish-speaking populations.
Financial Disclosure (Melissa Mims)
No
FDA Disclosure
Cleared:Yes
Keywords
Nurse
Social Worker
Training
Uninsured
Abstract ID: 65
Atomic Diagnostic In Cancer
Author List
1. Presenting Author: Valentin Curosu
2. Additional Author: Diana Haras
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Holmes Table.jpg
Summary
N/A
Introduction
Firstly, must exactly specify what biomatter(living matter) really is. Organismic self= normal organismic biomatter +
abnormal(tumoral) organismic biomatter. Because of its evolution to cachexia, cancer evidently is a disease of organism's
materiality. Cancer's (patho-)genesic mechanism: Genesic level of variable debiomaterialized tissue is reached by a
oncogenic disatomic quota, which is intravital tolerated only by a malignant cell genesis. Biomatter (to
level of cell as functional biomateril unit) has triple stucture.Biomateriality(troficity) of cell= sum of all its structural
bioatoms and parabioatoms. Materiality of cell = matter's quantity from all its bioatoms and parabioatoms. Last analysis,
cell has pure atomic substratum(H,O,N,C, more than 95%). Isoatoms and anionic disatoms of bioatoms and parabioatoms
enter aminoacids from cellular proteinic substratum. Vegetable and animal aminoacids are absorbed to intestinal level and
will form "probiomaterial organismic Field"(specific organismic proteins), which continually delivers necessary
aminoacids from organismic cell genesis.
Methods
Disatoms has a less materiality(atomic mass) than their isoatoms. Oncogenic disatoms are represented by anionic
intermediary disatoms of bioatoms(H,O,N,C) and parabioatoms(S,P,etc). Debiomaterializing oncogenic vectors reduce
tissue's troficity. Dematerializing oncogenic vectors reduce cell's materiality. To not die, when its materiality becomes a
underliminal one, tissue neoplasiates its cell genesis. By malignant cell genesis, tissue repairs its liminal missing
materiality. Always, tissue is biostructural level of neoplasic impact. There are FOUR CARDINAL
ONCOTHERAPEUTIC PRINCIPLES: 1.-eliminate malignant tumour(representing "organismic area of normal
biomatterhage"); 2.-stop each debiomaterializing oncogenic vector's action; 3.- supress oncogenic disatomic quota's action;
4.- iso-regenerate probiomaterial organismic Field. Only ATOMIC DIAGNOSTIC permits to find out how much is
debiomaterialized a neoplasiated tissue and so how to make it again a minimum liminal. Hystopatological examinations
permit to evaluate: how to dilute oncogenic disatomic quota, how to increase tissue's troficity, how to induce
MALIGNANT CELL'S APOPTOSIS BY UNDERLIMINAL MATERIALITY. etc.
Results
To treat a cancer having its atomic diagnostic is as to play a melody having its score. So many times there is an oncogenic
organismic Field, the malignant tumour's recurrence is not only a menace, but a rule.
Conclusion
Must eliminate the malignant cell to the last one, but in the same time, have to preserve each normal genesic cell from the
neoplasiated tissue.
Financial Disclosure (Valentin Curosu)
No
FDA Disclosure
Cleared:Yes
Keywords
atomic diagnosis
oncogenic vector
oncogenic disatom
oncogenic organismic Field
Abstract ID: 67
EMT Programs, Metastasis And Therapeutic Resistance In Claudin-low Breast Cancer
Author List
1. Presenting Author: Jana Knezevic
2. Additional Author: Jeffrey Rosen
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Breast cancer is the most prevalent cancer, and the second leading cause of cancer-related deaths in women. It is a
heterogeneous disease divided into multiple subtypes with different clinical outcomes. Our laboratory has developed a
novel transplantable genetically engineered p53-null model, which has the advantage of an intact immune system and the
appropriate microenvironment. A small subset of these tumors corresponds to the claudin-low breast subtype. Claudin-low
tumors exhibit mesenchymal properties, are resistant to conventional chemo and radiotherapy, and are enriched in
Tumor-Initiating-Cells (TICs). TICs exhibit decreased expression of certain microRNAs, critical for
Epithelial-Mesenchymal Transition (EMT). miR-200 family members are down-regulated in both normal mammary stem
cells and TICs, and represent part of a TGFÃŸ-regulated dual negative feedback loop with inducers of EMT, such as
Zeb1/2 and Snail. miR-200 expression is down-regulated in claudin-low tumors, so we hypothesized that restoring
miR-200 expression in these tumors will change their TIC profile, therapeutic sensitivity and metastatic potential.
Methods
In order to re-express the miR-200 members, we created doxycycline-inducible lentiviral constructs and transduced the
primary claudin-low (T11) tumor cells. We performed a reverse-phase protein array (RPPA) on the tumor samples to
determine the changes in the protein expression after up-regulation of miR200 family members. To determine whether the
induction of mir-200c renders the claudin-low tumors more sensitive to chemotherapy, mice were treated with doxycycline
and carboplatin in combination, or alone.
Results
We observed altered tumor histology, as the spindloid morphology changed into more epithelial-like structures
post-induction. RPPA analysis revealed that the epithelial marker E-cadherin was highly up-regulated after Dox treatment.
Additionally, the luminal marker keratin-8, not normally expressed in these tumors, following induction was re-expressed.
Tumors treated with doxycycline and chemotherapy also showed altered histology, increased macrophage infiltration and
increased apoptosis compared to control groups. The tumor growth rate significantly decreased.
Conclusion
MiR200 expression changed the morphological phenotype of the claudin-low tumors, as well as their growth properties.
Our model provides a unique opportunity to determine which step of the dissemination process requires the expression of
miR-200 members by inducing or repressing miR-200 family member expression at specific times during tumor
progression using both orthotopic transplantation into the cleared mammary fat pad and tail vein injection. Our longterm
goal is to enhance the chemosensitivity of TICs by regulating the expression of miR-200 at different stages of metastasis.
Financial Disclosure (Jana Knezevic)
No
FDA Disclosure
Cleared:Yes
Keywords
claudin-low
mir-200
EMT
TICs
Abstract ID: 68
Selective Histone Methyltransferase DOT1L Inhibitors Targeting MLL Translocated Leukemia
Author List
1. Additional Author: Justin Anglin
2. Additional Author: Lisheng Deng
3. Additional Author: Yuan Yao
4. Additional Author: Michele Redell
5. Additional Author: Shuo Dong
6. Presenting Author: Yongcheng Song
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
MLL (mixed lineage leukemia) gene translocated leukemia accounts for ~75% of infant and ~10% adult acute leukemia
with a particularly poor prognosis (survival <40%). There is therefore a pressing need to discover new drugs. Histone
H3-lysine79 (H3K79) methyltransferase DOT1L plays critical roles in the tumorigenesis of MLL translocated leukemia
and therefore represents a drug target for intervention. The first DOT1L inhibitor EPZ004777 was reported in July 2011
and showed selective activity against MLL leukemia. However, it has poor pharmacokinetics and more metabolically
stable DOT1L inhibitors are needed. Here, we show our independent work on DOT1L inhibitor discovery, development
and biological activity on MLL leukemia.
Methods
We used an integrated strategy of structure-base inhibitor design, medicinal chemistry, protein X-ray crystallography,
biological activity testing, QSAR and thermodynamic studies to discover and develop novel DOT1L inhibitors. Selected
inhibitors were further tested for their activities on MLL leukemia cell lines, MLL-oncogene transformed leukemia
initiating cells, as well as two in vivo MLL leukemia mouse models.
Results
Rational drug design and development have led to the discovery of several potent inhibitors of DOT1L with Ki values as
low as 0.5 nM. These inhibitors exhibit no or weak activities against four other representative histone lysine and arginine
methyltransferases, G9a, SUV39H1, PRMT1 and CARM1, showing excellent selectivity. X-ray crystallographic study of a
DOT1L:inhibitor complex reveals that the N6-substituent of the inhibitor, located favorably in a predominantly
hydrophobic cavity of DOT1L, provides the observed high selectivity. Structural analysis shows that it will disrupt at least
one H-bond and/or have steric repulsion for other histone methyltransferases. Structure activity relationship (SAR) and
quantitative SAR (QSAR) studies were performed, providing implications for future DOT1L inhibitor design. Isothermal
titration calorimetry (ITC) studies showed the binding of selected inhibitors to DOT1L are enthalpy-driven, and
competitive with the cofactor SAM (S-adenosyl-L-methionine), but not the substrate nucleosome. These compounds were
also found to have selective activity against the proliferation of MLL-translocated leukemia cells with EC50 values as low
as 4 ÂµM and promote differentiation of MLL leukemia initiating cells.
Conclusion
These compounds represent novel chemical probes for biological function studies of DOT1L as well as potential
therapeutics to treat MLL-rearranged leukemia.
Financial Disclosure (Yongcheng Song)
No
FDA Disclosure
Cleared:Yes
Keywords
Rational inhibitor design
Mixed lineage leukemia
structure activity relationship
chemical cancer biology
Abstract ID: 69
2012 Cervical Cancer Summit: Raising Awareness, Identifying Barriers
Author List
1. Presenting Author: Edith Silvas
2. Additional Author: Lois Ramondetta
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
A collaborative effort between MD Andersonâ€™s Cervical Comprehensive Cancer Control Workgroup, Cervical
Cancer-Free Texas, Houston Community College (HCC) Coleman College for Health Sciences, and Latinos Contra El
Cancer produced the cityâ€™s first annual Cervical Cancer Summit held January 31, 2012 at HCCâ€™s System
Administration Building. Texas State Representative Carol Alvarado helped kick-off the summit by presenting a resolution
in honor of the 2012 Cervical Cancer Summit.
Methods
Cervical cancer incidence and mortality rates among Hispanics and African Americans are higher in Harris County than in
Texas or the United States. In 2011, Harris County had 205 new cases of cervical cancer and 61 deaths from a disease that
is almost completely preventable. 
 
Conference attendees learned about the incidence and prevalence of cervical cancer in Houston and the surrounding area,
information on the human papilloma virus vaccination, evidence-based practices of CPRIT grant awardees, and how to
increase Texas Breast and Cervical Cancer Services participation. Table-top discussions and recruitment to work on the
following initiatives also occurred: 
 
Establishing a HPV/Cervical Cancer Navigation Network in Houston 
School-based Interventions/Education Programs 
2013 Cervical Cancer Summit 
Survivor Group/Establishing National Cervical Cancer Coalition (NCCC) Chapter 
CPRIT Going Forward/Opportunities for Collaboration and Addressing Gaps in Services and Barriers (e.g., submitting a
CPRIT grant: Reaching Women at Highest Risk for Cervical Cancer), and 
Curricula and Conversations: What we are teaching students, what we should be teaching students. 
Results
The summit brought together approximately 150 attendees, representing 40 local and state-wide organizations. Participants
included university and school-based nurses, health professionals from community clinics and academic settings, cervical
cancer survivors, and local community and political leaders. Forty community health workers also received two hours of
certified continuing education units (CEUs) and five hours of non-certified CEUs. The cervical comprehensive cancer
control workgroup is compiling a HPV / Pap resource directory that will be available online. Participants have followed up
on action items from the roundtable discussions.
Conclusion
The summit helped to establish a network of individuals dedicated to reducing the incidence and mortality rates of cervical
cancer in Houston and the surrounding area. Grant collaborations are underway; we are working to promote survivorship
issues and identify the gaps in services and resources that exist. Another summit will be held in January 2013, with plans to
host regional summits by 2014.
Financial Disclosure (Edith Silvas)
No
FDA Disclosure
Cleared:Yes
Keywords
cervical cancer
HPV
community health workers
survivors
Abstract ID: 70
ARF Regulates An Apoptosis-independent Barrier To Tumorigenesis In The Mammary Gland
Author List
1. Presenting Author: Vidya Sinha
2. Additional Author: Hua Dai
3. Additional Author: Yi Li
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
One candidate regulator of the antiproliferative tumor barrier in the mammary gland is the ARF tumor
suppressor, which has been reported to mediate apoptosis and senescence via both p53-dependent and p53-independent
mechanisms. ARF is dysregulated in many human tumors, including those arising from the prostate, breast, liver and lung
(Ozenne, 2010). Mice that have lost both copies of ARF are predisposed to sarcomas, lymphomas and
carcinomas, while those overexpressing ARF exhibit resistance to chemical-induced cancers (Matheu, 2004).
The role of ARF in mediating the apoptotic and senescence tumor barriers in the mammary gland remains controversial:
ARF appears to inhibit HER2/neu/ErbB2-mediated cell and xenograft tumor growth (Zhang, 2004); however
MMTV-ErbB2 mammary glands heterozygous for ARF do not exhibit increased tumor incidence
(Dâ€™Amico, 2003).
Methods
To assess whether the ARF-null mammary epithelium is able to erect an apoptotic and senescence response to
oncogene activation, ARF-null and wildtype mice were exposed to activated ErbB2 and either collected two
weeks post-injection for early lesions or palpated for 6 months for tumors.
Results
Early lesions from ARF-null mice exhibited increased proliferation, decreased senescence, but comparable
apoptosis relative to wildtype, suggesting that ARF may be dispensable for the apoptotic response in early lesions but is
necessary for a robust senescence response that may function as an important anti-proliferative barrier in mammary gland
epithelia. However, it remains unknown whether the observed loss of senescence and increased proliferation lead to a more
rapid development of palpable tumors. Preliminary results indicate that ARF-null mice indeed experience a
shorter mammary tumor latency compared to wildtype mice, suggesting the existence of a physiologically important
apoptosis-independent barrier to tumorigenesis in the mammary gland.
Conclusion
ARF may be dispensable for the apoptotic response in early lesions but is necessary for a robust senescence response that
may function as an important anti-proliferative barrier in mammary gland epithelia. Furthermore, ARF may mediate a
physiologically important apoptosis-independent barrier to tumorigenesis in the mammary gland.
Financial Disclosure (Vidya Sinha)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer
senescence
ARF
Cell cycle
Abstract ID: 71
A Genetic Platform For Deconstructing Mutant p53 Action
Author List
1. Presenting Author: John Abrams
2. Additional Author: Melissa Oneal
3. Additional Author: Nichole Link
4. Additional Author: Alejandro D'Brot
5. Additional Author: Annika Butler
6. Additional Author: Gianella Garcia Hughes
7. Additional Author: Erin Regan
8. Additional Author: Paula Kurtz
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
It is well-known that the human tumor suppressor p53 (hp53) is one of the most frequently mutated genes in human cancer.
This â€œguardian of the genomeâ€• functions as a transcriptional activation hub that promotes cell-cycle arrest, DNA
repair, or apoptosis in response to an arsenal of cellular stresses, such as DNA damage. However, in at least 75% of
cancers p53 acquires missense mutations which render it an oncogene, promoting more aggressive tumors which exhibit
increased invasiveness, metastasis and chemo and radio resistance. Knock-in mice models, together with sophisticated
tumor genotyping, have demonstrated these mutations to be â€œgain-of-functionâ€• and not mere loss-of-function or
dominant negative. The mechanisms by which these missense p53 mutants confer gain-of-function oncogenic activity are
largely unknown.
Methods
To address this problem, we have exploited Drosophila as a platform with which to study in vivo functions of human p53
mutations. Essentially, we have produced genetically identical Drosophila strains which substitute either wild-type or
mutant human p53 genes for the native fly counterpart.
Results
The wild-type strain expresses hp53 protein in an endogenous fashion, both in abundance and localization. Furthermore,
we have shown that the human p53 can genetically complement the fly counterpart and, in these strains, hp53 can bind the
dmp53 recognition element in vivo and trans activate dmp53 target genes. In addition, hp53 can promote
stimulus-dependent apoptosis in dmp53-/- animals. Successful complementation of Drosophila mutants with the wild type
human counterpart now sets the stage for the next phase of our analysis. Toward this goal, we have engineered five strains,
each of which produce p53 mutations most commonly seen in human cancers. Analyses of these are currently underway.
Conclusion
Systematic comparisons of phenotypes and molecular activities seen in these strains could enable discovery of universal
properties underlying oncogenic activity encoded by p53 mutations. Insights derived here could enable a dedicated
platform by which to stratify or group all p53 mutations seen in human cancers.
Financial Disclosure (John Abrams)
No
FDA Disclosure
Cleared:Yes
Keywords
hp53
Drosophila
apoptosis
dmp53
Abstract ID: 72
Estrogen Induces Metastasis Of TRP53 Negative Epithelial Ovarian Cancer Cells
Author List
1. Presenting Author: Lisa Mullany
2. Additional Author: JoAnne Richards
3. Additional Author: Zhilin Liu
4. Additional Author: Yi Ren
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
gfp-mice.jpg
Summary
Introduction
Ovarian cancer is a complex disease that is the fifth most lethal cause of death in women. Overwhelming evidence
documents a strong link between ovarian cancer subtypes and the status (wild type, mutant or null alleles) of the tumor
repressor protein, TP53. Wild type TP53 is expressed in low-grade serous adenocarcinomas in mice and women whereas
mutant or null alleles of TP53 are present in greater than 90% of all high-grade serous adenocarcinomas, the most prevalent
ovarian cancer subtype in women. The absence of functional TRP53 and genetic instability are the major defining features
of high-grade type ovarian cancers. Unfortunately, we do not yet understand how TP53 status relates to the
etiology/progression of this complex disease in women.
Methods
Because TP53 is mutated in the vast majority of human high-grade ovarian cancer, we deleted Trp53 in our
Pten/Kras/Amhr2-Cre mutant mouse model where serous adenocarcinomas develop and levels of wild-type TRP53 are
high. To determine if these Trp53 null tumors respond to estradiol, Trp53 positive and Trp53 null mutant mice were treated
with estradiol or vehicle. OSE cells were also injected intraperitoneally or subcutaneously (SC) into untreated and
estrogen-treated wild type mice. In addition, OSE cells were grown in matrigel and treated with combinations of estrogen,
progesterone or tamoxifen.
Results
When the ovarian cancer cells that lack Trp53 and express high levels of ESR1 are exposed to estradiol in vivo, the tumors
exhibit features characteristic of high-grade type ovarian cancer: enhanced, invasive growth into the ovarian stroma,
rampant metastases to the peritoneal cavity and signs of genomic instability. Estrogen promoted and progesterone blocked
the growth of Trp53 null tumor cells injected SC or when grown in matrigel. Progesterone and tamoxifen also inhibited
estrogen-induced growth and gene expression in Trp53 null cells grown in matrigel. By contrast, estradiol does not
augment tumor growth in the Pten/Kras mice where the mutant OSE cells express wild type TRP53 and low levels of Esr1.
Conclusion
Mouse ovarian tumor cells lacking functional Trp53 express increased levels of ESR1 and are remarkably responsive to
estradiol in vivo and in culture. These observations suggest that cancer cells lacking functional Trp53 may be highly
susceptible to unopposed estradiol and oncogenic insults at specific stages of tumor development and thereby have
relevance not only for women during their reproductive years but also in postmenopausal women on hormone (estradiol)
replacement therapies.
Financial Disclosure (Lisa Mullany)
No
FDA Disclosure
Cleared:Yes
Keywords
Ovarian cancer
P53
Estrogen receptor
Progesterone
Abstract ID: 73
Modulation Of The Thymic Microenvironment And Thymocyte: Stromal Crosstalk During T-ALL Progression
Author List
1. Additional Author: Kim Cardenas
2. Additional Author: Jessica Jones
3. Additional Author: Hilary Selden
4. Additional Author: Guadalupe Jasso
5. Additional Author: Coby Tran
6. Additional Author: Daniel Chupin
7. Presenting Author: Lauren Ehrlich
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
Introduction
As thymocytes develop, they modulate expression of receptors, such as chemokine receptors, that promote migration into
distinct thymic microenvironments. Within these thymic regions, developing T cells interact with heterogeneous stromal
cells, such as epithelial cells, dendritic cells, fibroblasts, and macrophages, which provide survival, selection, and/or
differentiation signals. Thymocyte: stromal crosstalk is essential for proper differentiation of both thymocytes and stromal
cells. In T cell acute lymphoblastic leukemia (T-ALL), molecular changes in developing T cells result in lymphoma
initiation. We hypothesize that altered signaling pathways in nascent lymphoma cells result in improper crosstalk with
thymic stromal cells, resulting in outgrowth of stromal subsets that feedback to support lymphoma proliferation and/or
survival.
Methods
We have identified alterations in the thymic microenvironment in a mouse model of T-ALL using immunofluorescent
analyses of thymic cryosections from LN3 mice at 1, 3, and 6 months of age, as well as from overt tumors. We have also
performed Collagenase IV/dispase digests of thymi from the same aged mice to prepare single cell suspensions of the LN3
thymi for multiparameter flow cytometric analyses, enabling us to quantify changes in stromal subsets during
lymphomagenesis. To visualize LN3 migration, 400 Î¼m thymic slices were vibratome sectioned from 1 month
Foxn1-Cre;mEGFP reporter mice. LN3 lymphoblasts were obtained from mice with acute T-ALL, stained with CMTPX,
incubated on the cut slices for â‰¥3 hours, and imaged via time-lapse 2-photon microscopy. 4D data tracking and image
processing was accomplished with Imaris (Bitplane) and ImageJ software
Results
LN3 mice display early and progressive disorganization of the thymic epithelium and displacement of
thymocytes/lymphoblasts away from the epithelium. In the epithelial-free zone, we find evidence for vascularization, a
network of atypical fibroblasts, and dendritic cells. Using 2-photon microscopy, we find that lymphoma cells migrate much
more slowly and tortuously on wild-type thymic stroma. Finally, we show that stromal cells are required for lymphoma
survival ex vivo.
Conclusion
Here we demonstrate that early and progressive alterations of the thymic microenvironment occur in this T-ALL prone
model, supporting our hypothesis that altered thymocyte: stromal crosstalk interferes with normal thymic organization
during T-ALL progression. Furthermore, T-ALL blasts migrate abnormally within a wild-type environment, suggesting
they fail to respond to normal migration cues from the thymic environment. We show that thymic stromal cells are required
for tumor survival ex vivo, consistent with the idea that the altered thymic microenvironment could supply
mitogenic or survival factors to T-ALL lymphoblasts.
Financial Disclosure (Lauren Ehrlich)
No
FDA Disclosure
Cleared:Yes
Keywords
T-ALL
T cell development
leukemia/lymphoma
tumor microenvironment
Abstract ID: 74
Delivery Of Training Curriculum To 2-1-1 Risk Specialists And Cancer Navigators
Author List
1. Presenting Author: Maria Fernandez
2. Additional Author: Katharine Ball Ricks
3. Additional Author: Sapna Prasad
4. Additional Author: Jazmine Cavazos
5. Additional Author: Ebun Odeneye
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Racial and ethnic minorities, the poor, the uninsured, and lower-educated individuals experience significant cancer-related
health disparities in Texas and across the nation. Late stage diagnosis of cancer, a key factor to survival, is also linked with
lower socioeconomic status, race and ethnicity. Therefore, it is vital to train telephone navigators and risk specialist as part
of an innovative, collaborative project between the University of Texas School of Public Health and 2-1-1 Helplines
(Houston and Weslaco) to motivate and assist these underserved populations to obtain free and/or low-cost screening and
preventive services for cervical, breast and colorectal cancers.Â
Methods
Using Intervention Mapping, we developed a three-day culturally-appropriate training to equip 2-1-1 personnel with
knowledge and skills for conducting preliminary risk assessment and navigation to increase participantsâ€™ adherence to
national recommendations for breast, cervical and colorectal cancer screenings. Training consisted of lectures, small-group
exercises and role-play activities. Modules include: culture and health, introduction to cancer navigation, cancer 101,
special topics in cancer, research ethics, health literacy, communication, protocols and processes.Â
Results
We trained a total of 6 cancer prevention navigators (4 in Houston, 1 in Weslaco and 1 in El Paso) and 39 risk specialists
(31 in Houston, 4 in Weslaco, & 4 in El Paso). Each initial training session spanned a three-day period with weekly
meetings and intermittent booster sessions based on personnel needs and emerging trends in survey data, such as
Motivational Interviewing and Problem Solving (MAPS) training and guest presentations by prominent referral sites and
physicians. Overall, navigators and risk specialists expressed confidence in their knowledge and ability to motivate, assist
and follow-up with 2-1-1 callers regarding mammograms, Pap tests, HPV vaccination and colorectal cancer screening.
Training evaluation called for an increased focus on medical presentations.
Conclusion
The training program enhances the multi-site intervention approach to cancer navigation. The inclusion of panel
discussions and case studies from real participant scenarios allowed navigators from all sites to share experiences and help
train each other using real-life lessons. Future booster sessions will incorporate this type of peer-to-peer training to enhance
the MAPS skills of the navigators and risk specialists. The training materials also help to achieve consistency across the
intervention results by offering the same modules to all navigators and risk specialists at the same time.Â
Financial Disclosure (Maria Fernandez)
No
FDA Disclosure
Cleared:Yes
Keywords
Training
Cancer Navigation
Disparities
Prevention
Abstract ID: 75
Characterization Of An Arachidonic Acid-deficient (Fads1 Knockout) Mouse As A Model For Identifying New
Drug Targets Upstream Of COX-2
Author List
1. Additional Author: Yang-Yi Fan
2. Additional Author: Jennifer Monk
3. Additional Author: Tim Hou
4. Additional Author: Evelyn Callaway
5. Additional Author: Logan Vincent
6. Additional Author: Brad Weeks
7. Additional Author: Peiying Yang
8. Presenting Author: Robert Chapkin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Arachidonic acid (20:4âˆ†5,8,11,14, AA)-cyclooxygenase (COX-2)-derived prostaglandins, e.g.,
PGE2, regulate inflammation and promote cancer development. A significant increase in COX-2 gene
expression has been shown to promote PGE2-dependent colon cancer development, in part, by enhancing cell
proliferation and repressing protective proapoptotic signaling pathways. Most studies to date have targeted prostaglandin
biosynthetic and degradation enzymes in an attempt to suppress PGE2. However, due to safety concerns
surrounding the use of pharmaceutical agents designed to target COX-2 and its downstream targets, it is important to
identify new targets upstream of COX-2. Therefore, we determined the utility of antagonizing tissue AA levels as a novel
approach to suppressing PGE2.
Methods
Mutant Fads1 (fatty acid desaturase 1, Î”5 desaturase) mice were generated using a gene-trapping technique.
Mice (strain C57BL/6) were cloned from an ES cell line (IST11525H2) carrying the fads1 allele disrupted by
the insertion of a gene trap vector with a lacZ (Î²-galactosidase)-neomycin resistance fusion cassette in the first intron. 
All animals were fed commercial 10% safflower oil diet, free of AA. In a separate experiment, the basal diet was
supplemented with ARASCO oil (containing 42% AA, w/w) to determine the effect of dietary AA on the life span of Null
mice. 
Total phospholipids in various tissues were extracted and separated by thin-layer chromatography. Fatty acids were
transesterified and analyzed by gas chromatography/mass spectrometry. Eicosanoids were extracted from various tissues,
and measured by combined high performance liquid chromatography-mass spectrometry. In vivo colonic cell proliferation
was determined by immunohistochemical detection, using the Click-It EdU assay. Immune cell populations were analyzed
by flow cytometry. 
Results
Systemic disruption of the fads1 (âˆ†5 desaturase) gene reciprocally altered the levels of dihomo-Î³-linolenic
acid (20:3âˆ†8,11,14, DGLA) and AA in mouse tissues, resulting in a profound increase in one- and
concurrent decrease in two-series-derived prostaglandins. The lack of PGE2 production was associated with
perturbed intestinal crypt proliferation, immune cell homeostasis, and a heightened sensitivity to acute inflammatory
challenge. In addition, Null mice failed to thrive, dying off by 12 weeks of age. Dietary supplementation with AA extended
the longevity of Null mice to levels comparable to Wild type and Heterozygous mice.
Conclusion
We have generated and characterized a novel AA-deficient (fads1 knock out) mouse model. We propose that
this new mouse model will expand our understanding of how PGE2 mediates inflammation and promotes
malignant transformation, with the eventual goal of identifying new drug targets upstream of COX-2.
Financial Disclosure (Robert Chapkin)
No
FDA Disclosure
Cleared:Yes
Keywords
fatty acid desaturase 1
dihomo-gamma-linolenic acid
prostaglandin
colon cancer
Abstract ID: 76
Characterization Of Osteosarcoma In Children, Adolescents, And Young Adults From South Texas: A 10 Year
Experience
Author List
1. Presenting Author: Aaron Sugalski
2. Additional Author: Allisha Jiwani
3. Additional Author: Yumin Chen
4. Additional Author: Cornell John
5. Additional Author: WIlliams Ronald
6. Additional Author: Josefine Heim-Hall
7. Additional Author: Jaclyn Hung
8. Additional Author: Anne-Marie Langevin
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Osteosarcoma is the most common bone malignancy diagnosed in children, adolescents, and young adults in the United
States. A recent analysis conducted by the Surveillance Epidemiologic End Results (SEER) branch from the NCI shows an
increased incidence of osteosarcoma in Hispanics. In most studies evaluating outcome of osteosarcoma, Hispanic patients
account for <15%. The University of Texas Health Science Center at San Antonio (UTHSCSA) Sarcoma Team serves a
predominantly Hispanic population, thus providing a unique opportunity for evaluating this population.
Methods
A retrospective analysis of demographics, tumor characteristics, response to treatment and survival outcome of all
osteosarcoma patients < 30 years of age diagnosed and treated at UTHSCSA between January of 2000 and December of
2009 was performed.
Results
Sixty children, adolescents, and young adults (median age 15, range: 2-28 years) were diagnosed with osteosarcoma during
this 10-year period. The cohort was comprised of 72% Hispanics. Metastases were present at diagnosis in 9 (15%) of the
patients and 56 (93%) of the tumors were located in an extremity. With a median follow-up of 35 months (range: 4-126),
patients with localized extremity tumors had a 5-year overall survival (OS) and disease-free survival (DFS) of 66% and
44%, respectively. We observed a statistically significant decreased 5-year DFS in patients diagnosed before age 12
relative to patients diagnosed between ages 12-29 (11% vs 54%, P=<0.001). Socioeconomic status (SES) based on family
income was available for 72% of the cohort. Family income was < $25,000 for 19 patients and > $25,000 for 24 patients.
There was no clinical or statistical correlation between SES data and tumor size or metastatic disease at presentation. We
also found that tumor necrosis was not directly predictive of outcome in our patients.
Conclusion
Our study demonstrated that in a predominantly Hispanic population, the preadolescent patients presented with aggressive
disease and had an increased rate of relapse when compared to previous studies. These observations and our finding that
tumor necrosis was not directly predictive of outcome suggests that the tumor biology and/or response to mainstay up-front
chemotherapy agents may be different in the Hispanic population, specifically in pre-adolescent patients.
Financial Disclosure (Aaron Sugalski)
No
FDA Disclosure
Cleared:Yes
Keywords
osteosarcoma
childhood
south texas
adolescents
Abstract ID: 78
Long Noncoding RNAs Link Transcriptional Regulation of Inflammatory Pathway Genes
Author List
1. Presenting Author: Bethany Janowski
2. Additional Author: Masayuki Matsui
3. Additional Author: Huiying Zhang
4. Additional Author: Yongjun Chu
5. Additional Author: Keith Gagnon
6. Additional Author: Sarfraz Shaikh
7. Additional Author: Satya Kuchimanchi
8. Additional Author: Muthiah Manoharan
9. Additional Author: David Corey
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 03:30 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Genome sequencing has revealed that most loci encode long noncoding RNAs (lncRNAs) that overlap the 5â€™ and
3â€™ termini of mRNA. Understanding lncRNAs is important because they may be central factors in a previously
unappreciated layer of genetic regulation. While the significance of many annotated lncRNAs remains under debate, recent
reports have implicated them in the control of transcription. We focused on the cyclooxyenase-2 (COX-2) gene because it
is a critical regulator of inflammation in normal physiology and disease. COX-2 catalyzes the conversion of arachidonic
acid to intermediates that are further metabolized to prostaglandins and other eicosinoids. These eicosanoids mediate
numerous biological processes including inflammation, development, reproduction, cellular immunity, cancer, and energy
homeostasis. Phospholipase A2 group IVA (PLA2G4A) is a cytosolic phospholipase that catalyzes the hydrolysis of
membrane glycerophospholipids to release arachidonic acid, the substrate for COX-2. The gene encoding PLA2G4A is
located on chromosome 1q25, adjacent to the COX-2 locus. The two promoters are organized head to head but are
separated by 149,000 bases. While the functions of COX-2 and PLA2G4A are intimately linked, nothing is known about
regulatory pathways that may connect their expression.
Methods
RNA Seq 
RIP 
qPCR 
western 
in vitro assay 
3C analysis 
5' and 3'-RACE 
transfection 
ChIP
Results
Although many long noncoding RNAs (lncRNAs) are discovered, their mechanism and function remain obscure. We
identify lncRNAs as critical regulators of basal and inducible COX-2 transcription. lncRNAs overlapping the COX-2
promoter are targets for ribonucleoprotein complexes containing complementary small RNAs and RNAi factors,
argonaute-2 and GW182. Recognition of lncRNAs by the RNAi machinery triggers recruitment of RNAP2 and
transcription factors, enhances COX-2 expression, counteracts repression by dexamethasone, and leads to >100-fold
super-activation of COX-2 expression when combined with pro-inflammatory stimuli. Activation alters histone marks and
requires the multifunctional scaffolding protein, WDR5. Gene looping allows long distance interactions between the
promoters of COX-2 and PLA2G4A, an adjacent inflammatory pathway gene. Endogenous miR-589 targets two adjacent
sequences within a promoter lncRNA to regulate basal COX-2 and PLA2G4A expression.
Conclusion
Our data demonstrate that a noncoding RNA network at the COX-2 promoter is controlled by miRNAs and organizes a
novel multi-gene inflammatory response pathway.
Financial Disclosure (Bethany Janowski)
material? Yes
Stock or stock option held in: Yes
- Pfizer
Royalties have been received from: Yes
- ISIS Pharm
- Alnylam Pharm
- RANA
FDA Disclosure
Cleared:Yes
Keywords
long non-coding RNA (lncRNA)
inflammation
COX-2
miRNA
Abstract ID: 80
Inference Of Signaling Network Perturbations Associated With PI3K Pathway Mutations In Endometrial Cancer
Author List
1. Presenting Author: Lydia Wai Ting Cheung
2. Additional Author: Gabor Balazsi
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
 
Cancer is a complex heterogeneous disease that results from accumulation of genomic aberrations reflected in signaling
network alterations. Identifying signaling network signatures involved in carcinogenesis greatly facilitates the development
of rational targeted therapy. Endometrial cancer is the most common gynecologic cancer but treatment options for
advanced or recurrent disease are limited and ineffective. The phosphatidylinositol 3â€™-kinase (PI3K) pathway has been
implicated in the etiology of endometrial cancer and therefore represents an ideal therapeutic target. Through sequencing
on 222 endometrial cancer patient samples, we have demonstrated frequent mutations in multiple PI3K family members
including PTEN (44%), PIK3CA (p110alpha catalytic subunit of PI3K; 40%) and
PIK3R1 (p85alpha regulatory subunit; 20%). Of particular interest, PIK3CA or
PIK3R1 mutations co-exist with PTEN heterozygous mutations at frequencies higher than
expected in contrast to most cancers, indicating the likelihood that they cooperate with PTEN aberrations in
the pathophysiology of endometrial cancer. High-throughput reverse-phase protein array show that PTEN protein loss is a
dominant effect resulting in PI3K pathway activation and that PIK3CA or PIK3R1 mutations
mimic PTEN loss in tumors where PTEN is heterozygously mutated and PTEN protein is retained, suggesting
that PIK3CA or PIK3R1 mutations might be co-selected with heterozygous PTEN
mutations to compensate for incomplete loss of PTEN protein.
Methods
In this study, correlation-based Relevance Networks are built after categorization of the patient samples into subgroups
based on PI3K pathway mutation status (single mutation or co-mutations).
Results
The results elucidate signaling network perturbations associated with different mutation and co-mutation patterns in
endometrial cancer.
Conclusion
Identifying signaling network signatures downstream of the mutations will aid the development of effective molecular
markers and therapeutic targeting in patients with different PI3K pathway aberrations.
Financial Disclosure (Lydia Wai Ting Cheung)
No
FDA Disclosure
Cleared:Yes
Keywords
Somatic mutation
Signaling network
None
None
Abstract ID: 82
DNMT3a And FLT3-ITD In A Mouse Model Of Leukemia
Author List
1. Presenting Author: Liubin Yang
2. Additional Author: Choladda Curry
3. Additional Author: Grant Challen
4. Additional Author: Margaret Goodell
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Figure.jpg
Summary
Introduction
Aberrant DNA methylation has been implicated in cancer development. De novo DNA methylation is mediated by DNA
methyltransferase (Dnmt) 3a and 3b. DNMT3A was recently found to be mutated in 20% of patients with acute myeloid
leukemia (AML) and 10% in myelodysplastic syndrome (MDS) by whole genome sequencing. We have demonstrated that
Dnmt3a deletion in mouse caused increased self-renewal of hematopoietic stem cells and an effective impairment of
differentiation. The deletion also caused aberrant methylation associated with oncogenes and tumor suppressor genes.
These findings suggest that aberrant DNA methylation is a novel mechanism for the initiation of leukemia. Since our null
mouse model of Dnmt3a alone was insufficient for malignancy, we hypothesized that secondary mutations are required for
leukemic transformation. In our Dnmt3a-ablated mouse model, we overexpressed FLT3 internal tandem duplication
(FLT3-ITD), a co-mutation found with DNMT3A in patients with AML.
Methods
Deletion of Dnmt3a in Dnmt3afl/fl; Mx1-cre mice was induced by injections of pIpC. Bone marrow from donor mice was
transduced with MSCV-GFP or MSCV-FLT3ITD-GFP retrovirus and transplanted into lethally irradiated recipients. The
mice were monitored monthly for development of malignancies by serial complete blood count (CBC) and peripheral
blood analysis by FACS and followed for disease latency. Moribund mice were sacrificed and analyzed for peripheral
blood smears, organ size, histology, GFP expression, and immunophenotype.
Results
Dnmt3a deletion with overexpression of FLT3-ITD caused rapid T-cell acute lymphoblastic leukemia/lymphoma (T-ALL)
in 6/8 mice with a median latency of 74 days compared to 106 days in WT mice overexpressing FLT3ITD (Figure 1). The
mice exhibited leukocytosis, splenomegaly, and thymomegaly with high GFP expression detected by FACS. Some
leukemic cells were CD4+CD8+ and some CD4-CD8-CD44+CD25- by flow cytometry. Furthermore, the leukemia was
transplantable to secondary recipients within 2 weeks.
Conclusion
Here, we show that Dnmt3a-ablated bone marrow cells are transformed into T-ALL upon overexpression of the oncogene
FLT3-ITD in a mouse bone marrow transplant model. While DNMT3A and FLT3ITD mutations have been mostly
described in myeloid malignancies, recent studies now describe myeloid gene mutations and myeloid/stem cell gene
expression patterns in a subset of high-risk T-ALL associated with poor prognosis termed immature or early T-cell
precursor leukemia. Our Dnmt3a-null-FLT3-ITD mice with T-ALL, is the first novel animal model of human immature
T-cell leukemia, which can provide valuable insight into the pathogenesis and treatment.
Financial Disclosure (Liubin Yang)
No
FDA Disclosure
Cleared:Yes
Keywords
leukemia
DNA methylation
DNMT3A
FLT3-ITD
Abstract ID: 83
Identification Of Kinases And Phosphatases Critical For ER-negative Breast Cancer Growth And Tumorigenicity
Author List
1. Presenting Author: Leroy Hubert
2. Additional Author: Abhijit Mazumdar
3. Additional Author: Petra den Hollander
4. Additional Author: Graham Poage
5. Additional Author: Powel Brown
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Estrogen receptor (ER)-negative breast tumors constitute 30% to 40% of breast cancers. Characterized by poor
responsiveness to traditional therapies, these tumors represent a major void in breast cancer treatment. We previously
defined transcripts overexpressed in ER-negative breast tumors and therefore may serve as novel pharmaceutical targets.
We hypothesize that inhibition of overexpressed kinases and phosphatases will suppress growth and tumorigenicity of
ER-negative breast cancer cells.
Methods
Specific kinases and phosphatases will be identified using in silico analysis of RNA microarray databases of
human breast cancers and by performing in vitro studies in human breast cancer cell lines. We will use the Oncomine
database to investigate expression levels and clinical prognoses of selected genes found to be overexpressed in human
breast cancers. We will then select 4 kinases and 4 phosphatases to investigate in vitro. ER-negative and
ER-positive breast cancer cells will be used to study the role of the selected genes. Inhibition of the selected kinases and
phosphatases will be achieved by RNAi or small molecule followed by the evaluation of cancer related molecular events
such as cell growth, cell cycle, apoptosis, and invasion. We will next isolate stable clones of ER-negative and ER-positive
breast cancer cell lines expressing inducible shRNAs to the genes found to be critical to these cancer relevant molecular
processes. These clones will then be used for xenograft experiments to test whether inhibition of the selected genes
suppresses ER-negative breast cancer growth in vivo. We will then determine the molecular mechanism by
which these proteins positively regulate ER-negative breast cancers.
Results
We have successfully identified a group of kinases and phosphatases that are overexpressed in ER-negative tumors. The
genes to be targeted are kinases: SGK1, RYK, PTK7 and SMG1 and phosphatases: PLD1, LPIN1, TIMM50 and DLGAP5.
Initial results from ongoing siRNA knockdown experiments targeting this group of genes suggest that inhibition decreases
cell growth of ER-negative cell lines, thus supporting our hypothesis. We anticipate having results of these studies within
the next 6 to 12 months.
Conclusion
Our initial studies have identified 4 kinases and 4 phosphatases as signaling molecules potentially critical for the growth
and tumorigenicity of ER-negative breast cancers. We are currently working to confirm these results, which will provide
detailed information on the role of these signaling molecules in regulating breast cancer growth and survival. Theses
studies will also provide important preclinical information to guide drug development for the treatment of ER-negative
breast cancer.
Financial Disclosure (Leroy Hubert)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer
Estrogen Receptor
Kinase
Phosphatase
Abstract ID: 84
Breast Screening & Patient Navigation For The Rural Underserved In North Texas
Author List
1. Presenting Author: Simon Craddock Lee
2. Additional Author: Trisha Melhado
3. Additional Author: Stephen Inrig
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
qinimage2.jpg
Summary
N/A
Introduction
Despite the national success of the CDCâ€™s Breast & Cervical Cancer Early Detection program, in Texas only a third of
counties could access a BCCS provider in 2010 and less than 1% of eligible women received mammograms through this
federal-state initiative. Consequently, North Texas reports suboptimal mammography rates, especially among rural
communities (US Census; Tx DSHS; BRFSS). To address these needs, we created a multi-county partnership to provide
comprehensive breast cancer screening and patient navigation (BSPAN) program for underserved women that preserves
local autonomy while integrating and coordinating evidence-based care.
Methods
Serving as a contractor for the Texas Breast & Cervical Cancer Services (BCCS), BSPAN leverages federal funds to
provide culturally sensitive services in collaboration with multi-sector local community partners (e.g., civic groups,
physician practices, community hospitals, churches) for underserved women across five North Texas counties. BSPAN has
three components: 1) Outreach & Health Promotion to reach underserved women; 2) Delivery & Navigation to guide
patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to fund mammography services
through our Texas BCCS contract, CPRIT funding, or local philanthropic funds. Investigators implemented the program
using highly visible community outreach events and aligned program implementation with rural community values
including altruism, privacy, and self-reliance.
Results
In two years, our partnership has screened over 3,600 women, 22% of whom were unscreened or had not had a
mammogram in 10 years. BSPAN patients came from vulnerable communities: 89% of symptomatic patients and 96% of
asymptomatic patients reported incomes less than 200% Federal poverty level. Over 80% of asymptomatic and over 90%
of symptomatic women lacked insurance. 30% of patients self-identified as Hispanic; nearly 10% preferred
Spanish-language services. Time to clinical resolution averaged 21.5 days; for symptomatic women, time to clinical
treatment averaged 13.5 days. Among both symptomatic and asymptomatic women, 80% were diagnosed with early stage
BC (Stage 0, I, II) in contrast to the Texas average of 60%.
Conclusion
A community network partnership can provide culturally-sensitive services to increase screening access, improve time to
diagnostic resolution, and facilitate timely referral to local treatment services in rural and underserved communities in
North Texas.
Financial Disclosure (Simon Craddock Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
screening
patient navigation
rural
uninsured
Abstract ID: 85
Evaluating A De-centralized Regional Model For Rural Breast Cancer Screening & Patient Navigation (BSPAN2)
Author List
1. Presenting Author: Simon Craddock Lee
2. Additional Author: Trisha Melhado
3. Additional Author: Stephen Inrig
4. Additional Author: Jasmin Tiro
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Mammography rates in the 12 rural counties targeted in our Breast Screening & Patient Navigation (BSPAN2) expansion
are suboptimalâ€” more than 74,000 screenâ€•eligible women have not had a mammogram within the past two years.
Initial CPRIT funding demonstrated that BSPAN1 is successful when we provide all the necessary resources to a rural
county. However, the complexity of providing outreach, navigation, and centralized reimbursement program components
in every locale constrains our ability to expand to other rural counties. To improve reach and sustainability, we are
evolving into a decentralized regional delivery model; we will train counties to take on outreach and/or navigation program
components while Moncrief/UT Southwestern continues to provide centralized reimbursement as a Texas BCCS
contractor.
Methods
Using the Glasgow RE-AIM strategy, we will: 1) assess which counties have the
resources and capacity to take on Outreach and/or Navigation components, and 2) train partners in each county to
implement program components based on local strengths. Finally, applying lessons learned from implementation in the test
counties, we will 3) assess and train 12 additional rural counties. RE-AIM specifies dimensions at the
participant and organizational levels. Dimensions are defined as the interventionâ€™s: 1)
Reach into the target population, 2) Effectiveness in increasing
screening, 3) Adoption by county partners, 4) consistent
Implementation, and 5) Maintenance of its effects among
participants and county partners. Including both the individual and county levels in the framework allows for investigation
of whether an intervention has an impact on one level but not the other. Our mixed-methods approach, focused at both
levels, will determine how our model adapts to local settings and how we impact screening for the rural underserved
overall.
Results
Our team is developing an assessment tool, training curricula, and internet-based patient tracking database application that
can be used to disseminate this decentralized regional model for the delivery of mammography services to rural
communities across the country.
Conclusion
The RE-AIM model can be used to evaluate the sustainability of a decentralized regional delivery model for breast cancer
screening services. It capitalizes on local community strengths to adapt and maintain delivery infrastructure to provide care
for underserved residents. This standardized expansion will enable partners in the five current and 12 new counties to
increase screening access, improve time to diagnostic resolution, and facilitate timely referral to local treatment services for
breast cancer while developing tools needed to disseminate a de-centralized model of effective service delivery.
Financial Disclosure (Simon Craddock Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
evaluation
sustainability
RE-AIM
patient navigation
Abstract ID: 86
Structure Of Human Mad1 C-Terminal Domain Reveals Its Kinetochore-Targeting Function
Author List
1. Presenting Author: Soonjoung Kim
2. Additional Author: Hongbin Sun
3. Additional Author: Hongtao Yu
4. Additional Author: Xuelian Luo
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The spindle checkpoint prevents aneuploidy by delaying anaphase onset until all sister chromatids achieve proper
microtubule attachment. The kinetochore-bound checkpoint protein complex Mad1â€“Mad2 promotes the conformational
activation of Mad2 and serves as a catalytic engine of checkpoint signaling. How Mad1 is targeted to kinetochores is not
understood.
Methods
Here, we report the crystal structure of the conserved C-terminal domain (CTD) of human Mad1. 
Results
Mad1 CTD forms a homodimer and, unexpectedly, has a fold similar to that of the kinetochore-binding domain of Spc25.
Mutagenesis studies validate a role of Mad1 CTD in kinetochore targeting and implicate Bub1 as its receptor. Deletion of
the CTD does not abolish Mad1 kinetochore localization. Non-overlapping Mad1 fragments retain detectable kinetochore
targeting. 
Conclusion
Our results indicate that CTD is a part of an extensive kinetochore-binding interface of Mad1, and rationalize graded
kinetochore targeting of Mad1 during checkpoint signaling.
Financial Disclosure (Soonjoung Kim)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 87
Development Of Multistage Vectored siRNA Therapeutics For The Treatment Of Breast Cancer
Author List
1. Presenting Author: Haifa Shen
2. Additional Author: Mauro Ferrari
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
RNA interference has the potential to specifically knock down the expression of target genes, and thereby transform cancer
therapy. However, lack of effective delivery of small inhibitory RNA (siRNA) has dramatically limited its in vivo
applications. We have developed a multistage vector (MSV) system, composed of discoidal porous silicon particles loaded
with siRNA oligos packaged in dioleoyl phosphatidylcholine (DOPC) nanoliposomes, that directs effective delivery and
sustained release of siRNA in tumor tissues. We proposed to target the DNA damage repair pathways by multistage
delivery of ATM siRNA to sensitize treatment of breast cancer. As the first step in the development of MSV/ATM siRNA
as a therapeutic agent for breast cancer, we evaluated the acute and sub-acute toxicities of this candidate drug to ensure its
benign safety profile.
Methods
ATM siRNA oligos were packaged into DOPC nanoliposomes, and loaded into the MSV microparticles. To assess acute
toxicity, BALB/c mice were treated once with either free liposomal scramble or ATM siRNA or MSV-loaded siRNA.
Serum samples were collected 3 and 6 hours later, and levels of 32 cytokines and chemokines were measured. To detect
potential sub-acute toxicity, mice were treated weekly with either free liposomal scramble or ATM siRNA or MSV-loaded
siRNA for four weeks. Body weight and behavior changes were monitored during treatment. At the end of the treatment,
hematological analysis was carried out to measure changes in blood cell counts, blood biochemistry was analyzed to
evaluate changes in liver and renal functions, and histological examination of major organs including brain, heart, kidney,
liver, lung, and spleen was performed to check abnormalities.
Results
No measurable changes were detected in serum pro-inflammatory cytokines, chemokines or colony-stimulating factors at
therapeutic doses from free liposomal ATM siRNA or MSV/ATM siRNA. Repetitive treatment of mice with free ATM
siRNA or MSV/ATM siRNA for 4 weeks did not cause significant changes in body weight, hematology, blood
biochemistry, or major organ histology.
Conclusion
The safety profile of MSV/ATM siRNA from the current study warrants further development of this candidate drug for the
treatment of breast cancer.
Financial Disclosure (Haifa Shen)
No
FDA Disclosure
Cleared:Yes
Keywords
multistage vector
siRNA
delivery
toxicity
Abstract ID: 89
Breast Cancer Intrinsic Subtype Specific Interactions With The Microenvironment Dictate The Mechanism Of
Tumor Invasion
Author List
1. Presenting Author: Tuyen Dang
2. Additional Author: Gray Pearson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Breast cancer patients mortality is a consequence of the metastatic dissemination of neoplastic cells into foreign tissues, not
the primary tumor growth. Fibroblasts located in the breast microenvironment may trigger neoplastic cells to invade out of
the mammary duct and into the stroma, an early step in breast cancer metastasis. Investigating how mammary fibroblasts
promote breast cancer invasion may improve both treatment and the accuracy of diagnosis of breast cancer patients.
Methods
We have found that mammary fibroblasts specifically induce the invasion of basal-type breast cancer cells. The propensity
of the mammary fibroblasts to induce the invasion of the basal-type breast cancer cells correlated with the reorganization of
the collagen in the microenvironment. Secreted factors from the mammary fibroblasts were insufficient to induce invasion
of the neoplastic cells. Instead, we discovered that the Cdc42 dependent reorganization of stromal collagen by the
mammary fibroblasts was necessary for the induction of basal-type breast cancer cell invasion.
Results
To determine how the basal-type breast cancer cells opportunistically invaded into paths created in the stromal collagen,
we imaged an organotypic culture model in real-time. The live-imaging revealed that basal-type breast cancer cells within
spheroids were motile and constantly exchanging cell-to-cell partners within the confines of the sphere. In contrast, the
luminal-type breast cancer cells were not motile within the spheroids. When co-cultured with fibroblasts, the basal-type
breast cancer cells that invaded through paths created in the collagen were motile cells. The static luminal-type breast
cancer cells were not able to leave the spheroids and invade into the stroma. Thus, the intrinsic ability of the basal-type
breast cancer cells to move within multicellular spheroids promoted the invasion in response to the accumulation of nearby
mammary fibroblasts. 
 
Cell motility is a complex process with many regulatory components including microRNA dependent control of gene
expression. Expression profiling of patient and breast cancer cell lines has demonstrated that there is differential
microRNA expression between the basal and luminal breast cancer subtypes. We are currently exploring how intrinsic
subtype specific microRNA expression contributes to the differential motility observed between the basal and luminal
breast cancer cells. 
Conclusion
In conclusion, our data suggest that mammary fibroblasts are sufficient to induce motile basal-type breast cancer cells to
invade into the stroma and we are investigating how basal-type breast cancer microRNA expression promotes cell motility.
Financial Disclosure (Tuyen Dang)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer
Tumor microenvironment
Cell motility
microRNA
Abstract ID: 90
Comparison Of Image Analysis Methods For The Segmentation Of The Zebrafishâ€™s Embryonic Anatomical
Structures
Author List
1. Presenting Author: Eleni Zacharia
2. Additional Author: Noah Kessler
3. Additional Author: Sharanya Maanasi Kalasekar
4. Additional Author: Maria Bondesson
5. Additional Author: Jan Ake Gustafsson
6. Additional Author: Ioannis A. Kakadiaris
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Zebrafish obtain their nutrition from the maternally derived yolk during their first week of life. If the yolk for some reason
cannot be absorbed, the embryos are affected by malnutrition resulting in small size and developmental defects, a condition
termed embryonic malabsorption syndrome (EMS). Pharmaceutical lipid regulators such as clofibrate and gemfibrozil,
found in surface, ground, and drinking waters, have been shown to cause EMS in zebrafish. Transgenic fish expressing
GFP in the yolk sac, eyes, and heart can serve as an excellent model system, through which we are able to visualize the size
of the yolk sac during normal and chemically perturbed yolk absorption. Quantifying the size of the yolk sac enables us to
determine the toxicity of a given chemical.
Methods
On the fifth day of embryonic life, the zebrafish is imaged using fluorescent microscopy. The acquired images depict the
fishâ€™s yolk sac, eyes, and heart with higher intensity than the rest of the fish. Three different approaches have been
implemented for the segmentation of these images. The first approach implements the Active Appearance model method.
The second approach is based on a geometric 2D atlas of the anatomical structures of the transgenic zebrafish expressing
fluorescent proteins. This atlas is represented by a subdivision mesh and it is deformed to fit optimally to each zebrafish
depicted in each image. The third approach is based on an iterative process through which the parameters of gamma
correction are tuned. Subsequently, the contours of the anatomical structures of the transgenic fish are determined based on
the image intensities, values, and edges.
Results
Several experiments were performed to evaluate the accuracy of the proposed approach on the segmentation of images
depicting the anatomical structures of transgenic zebrafish expressing GFP. Fifty images were used for the validation of the
first and second approach and 320 for validating the third approach. The ground truth was obtained through manual
annotations. The evaluation of the proposed approaches was based on the Dice Similarity Coefficient. For the first
approach the average Dice was 81.47, 63.70, 67.28, and 62.52 for the yolk, right eye, left eye, and heart, respectively. For
the second approach the average Dice was 93.47, 84.55, 85.47, and 70.52. For the third approach the average Dice was
93.20, 84.54, 85.75, and 73.57.
Conclusion
Three different approaches have been developed for the segmentation of the zebrafishâ€™s embryonic anatomical
structures.
Supported by a training fellowship from the Keck Center Computational Cancer Biology Training Program of the Gulf
Coast Consortia (CPRIT Grant No. RP101489). 
Financial Disclosure (Eleni Zacharia)
No
FDA Disclosure
Cleared:Yes
Keywords
image analysis
segmentation
zebrafish
fluorescent microscopy
Abstract ID: 91
Post Transcriptional Regulation of Induced Myeloid Leukemia Cell Differentiation Protein (Mcl-1)
Author List
1. Presenting Author: Arindam Chaudhury
2. Additional Author: Joseph Fachini
3. Additional Author: Anita Chandler
4. Additional Author: Natee Kongchan
5. Additional Author: Joel Neilson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Over 50% of the genes in the human genome undergo Alternative Cleavage and Polyadenylation (APA), altering the
identity of the 3' untranslated region (UTR) of mRNA transcripts without impacting their coding sequences. Enhanced
cleavage at proximal PAS resulting in global 3â€™-UTR shortening has been linked to cellular differentiation,
proliferation and neoplastic transformation. APA modulates the cognate transcriptsâ€™ visibility to the
post-transcriptional regulatory machinery; however, the actual impact of different isoforms derived from a particular
genomic locus to the ultimate functional expression of that locus remains largely unexplored. Using targeted
high-throughput sequencing techniques, we have assessed APA in a broad panel of primary and transformed hematopoietic
cell types and pathologies. One gene consistently represented by more than one 3' UTR transcript isoform in this study is
the Mcl-1 gene, which encodes a conserved member of the Bcl-2 family of proteins and is overexpressed in a variety of
human hematopoietic and solid organ malignancies. Our goal is to define how APA at the Mcl-1 locus contributes to the
aggregate functional expression of the Mcl-1 gene in normal and transformed cells.
Methods
We utilized a panel of human hematopoietic cancer cell lines as an in vitro model of Mcl-1 transcript isoform variation in
response to cellular stresses associated with tumorigenesis in vivo, and its concomitant impact on Mcl-1 protein expression
and gene function. Pulse-chase assays were employed to assess mRNA and protein stability, and polyribosome
fractionation analysis was used to assess ribosomal occupancy of individual isoforms. To assess the response of individual
isoforms to cellular stimulus, we utilized luciferase reporters and a novel piggyBac-based reporter platform. The impact of
isoform-specific siRNA knockdown of Mcl-1 transcripts was also assessed.
Results
Post-exposure to stresses associated with tumorigenesis in vivo, the steady state Mcl-1 protein expression is increased in
human cancer cell lines that were not attributable, with one exception, to differential protein turnover rates. Polyribosome
fractionation analysis revealed context dependent patterns of Mcl-1 3-UTR isoformsâ€™ localization to either the actively
translating, polysomal or thcre translationally inactive non-polysomal pools. In fact, selective siRNA-mediated knockdown
of the different Mcl-1 isoforms differentially impacts Mcl-1 protein expression.
Conclusion
Mcl-1 isoforms resulting from APA are differentially regulated in cell and context dependent fashion. We are currently
performing experiments to define the functional relevance of this process in defining the critical balance between cell
survival and death during neoplastic transformation.
Financial Disclosure (Arindam Chaudhury)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 92
Cancer Knowledge And Health Perspectives Of Individuals With Intellectual And Developmental Disabilities
Author List
1. Presenting Author: Stephanie Schirber
2. Additional Author: Lex Frieden
3. Additional Author: Vinh Nyugen
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
There is increasing evidence to suggest individuals with intellectual and developmental disabilities (IDD) are not receiving
appropriate health care information and services. Individuals with IDD exhibit a high prevalence of obesity and chronic
conditions, including cardiovascular problems and osteoporosis (Wilkinson et al., 2007, Perkins and Moran, 2010).
Disparities in administration of appropriate preventative care have also been found, including lower rates of certain cancer
screenings (Parish et al., 2006, Tyler et al., 2010). The objective of this study was to obtain the perspectives on health,
knowledge of cancer, and experiences with primary health care providers of individuals with IDD in the Houston
community.
Methods
Two focus groups were held with 5-8 subjects per session, with a total of 13 participants. Participants were recruited from
Houston organizations offering services to individuals with IDD. The discussion was organized around three topics: health,
cancer, and experiences with primary health care provider. Discussion was audio recorded and later transcribed for
identification of common themes and anecdotal information.
Results
Health: Participantâ€™s awareness of general health information was promising. Weaker responses were provided
regarding whether participants apply these health practices to their own lives. Participants described obtaining health
information from radio, television, and caregivers. Doctor: All participants reported having a family member or staff
accompany them to the doctor, as well as facilitate appointment scheduling. All responses on talking with the doctor were
positive, agreeing their doctor spoke to them in a way they could easily understand. Fear of certain tests or of receiving bad
news were reported as negative experiences at the doctor. Cancer: Knowledge of cancer was generally poor and at times
inaccurate. Only one participant indicated that they had ever had a cancer screening, or had ever been talked to about
cancer screening. Anxiety over getting cancer was consistently expressed.
Conclusion
As the awareness of beneficial and harmful health practices was promising, education on general health should not be the
top priority. Although participants reported positive experiences with health care providers, there may be limitations to
these responses. In particular response bias, or wanting to avoid addressing sensitive issues regarding their disability. As
caregivers are a key component of these individualsâ€™ medical care, they should be included in educational
programming. In order to improve preventative cancer knowledge and screenings, education on the importance of
screenings, ways to manage anxiety, and how to advocate their needs should be the focus.
Financial Disclosure (Stephanie Schirber)
No
FDA Disclosure
Cleared:Yes
Keywords
intellectual and developmental disability
health knowledge
focus groups
preventive health services
Abstract ID: 93
Systematic Discovery Of Oncogenotype Selective Vulnerabilities
Author List
1. Presenting Author: Hyun Seok Kim
3. Additional Author: John Minna
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Non small cell lung cancer (NSCLC) remains one of the most common and fatal cancers. Although targeted therapy is
available for a small group of patients with EGFR mutations or ALK fusions, most cancers remain refractory to current
interventions.
Methods
We employed a systematic approach for discovery of genetic vulnerabilities, in the context of a matched pair of
immortalized normal (HBEC30) and tumor (HCC4017) cell lines from a same patient, using one-gene/one-well based high
throughput siRNA screening platforms. We further assessed the penetrance of the isolated tumor-line specific monogenic
lethals within an expanded cancer (21) and normal (2) cell panel.
Results
By associating RNAi toxicity profiles with 10 major oncogenotypes, we discovered dependency of KRAS/LKB1 double
mutant tumor-derived lines, previously characterized as a highly aggressive oncogenotype, on coatomer complex I (COPI)
for their survival. These double mutant lines share gene expression signatures with the claudin low cancer stem cell like
breast cancer subtype again metastatic and one of the most aggressive subtypes.
Conclusion
Isolation of small molecules with similar selective toxicity profiles is now being used to generate intervention leads.
Financial Disclosure (Hyun Seok Kim)
No
FDA Disclosure
Cleared:Yes
Keywords
NSCLC
KRAS
RNA interference
COPI
Abstract ID: 94
Purinergic Signaling In Hepatocellular Carcinoma
Author List
1. Presenting Author: Janielle Maynard
2. Additional Author: Randy Johnson
3. Additional Author: John Goss
4. Additional Author: Sundararajah Thevananther
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Hepatocellular Carcinoma (HCC) is the third lethal cancer worldwide. Despite its increasing incidence the cellular and
molecular mechanisms of pathogenesis are not well understood. Previous findings from our laboratory suggest that
extracellular ATP via activation of P2Y2 purinergic receptors induce hepatocyte proliferation in response to partial
hepatectomy and ATP treatment alone was sufficient to induce hepatocyte proliferation in vitro. The purpose
of this study was to examine the role of purinergic signaling in the pathogenesis of HCC in patients and
Mst1/2-/-, a mouse model of HCC. Mst1/2 kinase activates the hippo signaling pathway which induces tumor
suppression, via phosphorylation of LATS1/2 and Yap preventing nuclear translocation of Yap, which promotes
transcription of pro-proliferative and anti-apoptotic genes. Hypothesis: Dysregulation of
purinergic signaling facilitates aberrant cell proliferation underlying hepatocellular carcinogenesis.
Methods
Mst1/2-/- mice livers (1, 3, & 6 months) were analyzed by qRT-PCR and Western blotting for P2 purinergic
receptor expression. HCC-derived Huh7 cells were treated with P2 receptor agonists; ATPgS, ATP, ADP, UTP (100uM)
for different time intervals. HCC patient samples (n=27) were evaluated by qRT-PCR for expression of all 15 P2 receptor
isoforms.
Results
Mst1/2-/- mice which develop liver tumors (3-6 months) exhibit distinct differences in temporal profile of
multiple P2 purinergic receptor isoforms, as compared to WT. As evidence for functional interaction between purinergic
and hippo signaling pathways, ATPgS, ATP, ADP or UTP treatment alone was sufficient to induce early Mst1/2
phosphorylation in Huh7 cells. Indicative of inactivation of Mst1/2-mediated tumor suppression in Huh7 cells, ADP
treatment decreased Yap phosphorylation and increased nuclear translocation of Yap protein, despite upstream activation
of Mst1/2 and LATS1 phosphorylation. In HCC patients, multiple P2 receptor isoforms were elevated >2-fold in liver
tumors as compared to uninvolved areas in up 50% of patients. P2 purinergic receptor upregulation was more prevalent
among HCC patients infected with Hepatitis C Virus (HCV) as compared to non-viral groups (75% vs 20%; HCV vs
non-HCV) identifying a unique subset of viral-induced HCC over-expressing P2 receptors.
Conclusion
Our analysis of HCC patient and Mst1/2-/- mice livers has uncovered a potential role for purinergic signaling in the
pathogenesis of HCC. We have identified extracellular nucelotide-mediated purinergic signaling as a novel upstream
modulator of hippo tumor suppressor kinases Mst1/2 and LATS1 with dysregulation of purinergic-hippo signaling
interactions in Huh7 cells. These findings highlight the potential for P2 purinergic receptors as potential biomarkers and
novel therapeutic targets for HCC.
Financial Disclosure (Janielle Maynard)
No
FDA Disclosure
Cleared:Yes
Keywords
Purinergic Signaling
Hepatocellular Carcinoma
Hippo Pathway
Hepatitis C Virus
Abstract ID: 95
Seton Healthcare Family Colorectal Screening: A Pilot Program
Author List
1. Presenting Author: Angela Cook
2. Additional Author: Heidi Herndon
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The USPSTF has recommended highly sensitive FOBT, sigmoidoscopy, and colonoscopy for CRC screening based on
substantial evidence, and has not favored recommending one test over another. Evidence suggests similar life years gained
by screening with any of these tests. The similar life years gained for all recommended tests supports the concept that
enabling a patient to participate in any screening strategy is more important than which strategy is chosen. This pilot
program was modeled after the UT Southwestern Colorectal Screening Program. Purpose/Objectives: To implement a
colorectal cancer screening pilot program to improve screening rates among adults ages 50-75 years at a Seton Healthcare
Family Clinic which primarily serves minority and underfunded patients.
Methods
300 packets including Fecal Immunohistochemical Tests (FIT), surveys (English/Spanish) and a letter explaining the
purpose of the packet were mailed to patients who have been seen within the previous year. Phone calls were made prior to
receipt of packets, two weeks after mail out and 30 days after mail out. Positive FIT kits and/or positive surveys led to
follow up with primary care physician for appropriate referral to GI clinic.
Results
A 25% return rate (75 responses) is expected. Descriptive statistics, including: patient demographics, time from positive
FIT test to completion of pre-colonoscopy evaluation, as well as colonoscopy will be determined for this pilot project
Conclusion
This pilot project is in the midst of data collection. Analysis will be concluded by end of August 2012. Lessons learned will
be shared.
Financial Disclosure (Angela Cook)
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal Screening
FIT testing
Underserved
Minority
Abstract ID: 96
Time to Blood Resolution Curves In Prostate MRI: T1, T2, and T2* Epi Signal Curves at 3.0t MRI
Author List
1. Presenting Author: Rulon Hardman
2. Additional Author: Yi Zhang
3. Additional Author: Vijayanadh Ojili
4. Additional Author: Alampady Shanbhogue
5. Additional Author: Ian Thompson
6. Additional Author: Qi Peng
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
left prostate hemorrhage.jpg
Summary
Introduction
One source of false positive on prostate MRI on prostate cancer diagnosis is the presence of hemorrhage in the prostate
after transrectal biopsies. The purpose of this study is to evaluate the hemorrhage resolution curves of T1W turbo spin echo
(TSE), T2W TSE, and T2*W echo planar imaging (EPI) magnetic resonance imaging (MRI) sequences in a prospective
patient cohort referred for clinical MRI.
Methods
This is a HIPAA compliant, IRB approved, prospective trial. 55 men enrolled in this prospective trial and underwent
prostate MRI with T1W axial, T2W axial, and susceptibility imaging by a 2D EPI sequence at 3.0T with endorectal coil.
Image excitation for the T2*W EPI sequence was performed using a 2D spatial RF excitation pulse with spiral k-space
trajectory, scan duration = 30 seconds. Time after biopsy ranged from 3 weeks to 10 years, with 66% of men having a prior
biopsy within 5 months of the MRI. The signal of areas of hemorrhage were plotted against time from biopsy. Contrast of
T1W and T2*W images are compared for diagnostic ease of interpretation.
Results
Signal change persists on T2* EPI images in areas of hemorrhage greater than what is seen on T1W images. T2* EPI
shows greater contrast in identifying calcium than T1 images. Results suggest that hemorrhage may alter T2W signal
intensity beyond the 6 weeks that is currently recommended to wait after biopsy to undergo prostate MRI.
Conclusion
The hemorrhage evolution curves of hemoglobin are more delayed than previously known. These curves should be taken
into consideration with image interpretation and time to scan after biopsy.
Financial Disclosure (Rulon Hardman)
No
FDA Disclosure
Cleared:Yes
Keywords
mri
prostate cancer
hemorrhage
T2*
Abstract ID: 97
Gemcitabine Resistance To Human Pancreatic Cancer Cell Line BxPC3 Is Associated With EMT, Cancer Stem Cell
Markers And miRNA Profile
Author List
1. Presenting Author: Alakesh Bera
2. Additional Author: Kolaparthi VenkataSubbaRao
3. Additional Author: Shujie Zhao
4. Additional Author: Lindsay Peterson
5. Additional Author: James Freeman
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 02:15 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In spite of new therapeutic strategies, human pancreatic ductal adenocarcinomas (PDAC) remain one of the greatest
oncological challenges, as the rate of incidence almost equals the rate of mortality with a 5-year survival of less than 5%.
Gemcitabine is the standard therapy for PDAC and is mostly used alone or in combination with an EGFR inhibitor. While
tumors respond to Gemcitabine treatment initially, they generally develop chemoresistance. In this present study we
investigate the molecular events that promot resistance to Gemcetabine in pancreatic cancer cells BxPC3. 
Methods
A thorough understanding of molecular mechanism which leads to resistance against Gemcitabine may identify pathways
that can be efficiently targeted to reverse chemoresistance. A cell line model resistant to Gemcitabine was generated by
transiently exposing BxPC3 cells to increasing concentrations of Gemcitabine.
Results
This Gemcitabine resistant cell line, BxPC3-GzR, was compared with untreated BxPC3 control cells. BxPC3-GzR cells
showed properties of undergoing epithelial to mesenchymal transition (EMT) and these included spindle shaped
morphology, an increase in expression of vimentin and a decrease in expression of E-cadherin. BxPC3-GzR cells also
showed an increase of expression of CD44 and in expression of phosphorylated STAT3TY705, which are characteristic of
cancer stem cells. BxPC3 and BxPC3-GzR where further compared by microarray analyses for expression of micro-RNAs
(miRNAs). This chemoresistance mesenchymal phenotype (CRM-phenotype) BxPC3-GzR cells showed a specific miRNA
expression profile (9 positively and 8 negatively regulated). Thus far seven of eight miRNAs identified as altered in
BxPC3-GzR cells were validated by real-time RT-PCR (miR-15b, miR-21, miR-100, miRNA -125b, miRNA-155,
miR-205 and miR-455-3p).
Conclusion
These studies suggest that Gemcitabine treatment of PDAC selects for a resistant population of tumor cells that have a
mesenchymal/stem cell-like phenotype and that express a distinct miRNA profile. Targeting these miRNAs may provide
novel targets for restoring or enhancing anti-tumor response of Gemcitabine.
Financial Disclosure (Alakesh Bera)
No
FDA Disclosure
Cleared:Yes
Keywords
pancreatic cancer
Gemcitabine
micro-RNA
Stem cell marker
Abstract ID: 98
Engineering Mesenchymal Stromal Cells (MSC) To Deliver Adenoviral Vectors That Eliminate Normoxic And
Hypoxic Tumor Cells Through Suicide Genes
Author List
1. Presenting Author: Valentina Hoyos
2. Additional Author: Miki Ando
3. Additional Author: Gianpietro Dotti
4. Additional Author: Carlos Ramos
5. Additional Author: Malcolm Brenner
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Following intravenous administration, MSCâ€™s concentrate in the lung and can traffic to areas of inflammation and
tissue destruction. We have therefore engineered MSCs to deliver signals that will activate apoptosis in dividing and
non-dividing (hypoxic) lung tumor cells. To maximize delivery of these signals we modified MSC to release two
adenoviral vectors at the tumor site. The first encodes an inducible caspase 9 (iC9) suicide gene that is rendered selective
for non-dividing (hypoxic) tumor cells by incorporation of hypoxia response elements (HRE), while the second contains
the Tyrosine Kinase (Tk) suicide gene which leads to death of dividing tumor cells.
Methods
We generated MSCs from human bone marrow and transduced them with a retroviral vector encoding the adenovirus E1A
gene. After demonstrating expression of E1A by immunofluorescence, we showed adenovector production following
transduction with an adenovirus-GFP vector by adding supernatant from these engineered MSC to H1299 lung cancer cells
and quantifying GFP expression. We then constructed two Adenoviral vectors; one contained iC9 and truncated CD19
(used as a marker), driven by HREs (Ad.iC9); the second contained TK and GFP (Ad.Tk). We measured the expression of
these vectors after transduction of H1299 tumor cells, and then determined the anti-tumor activity of each by adding to the
culture AP1903, a chemical inducer of iC9 dimerization (CID) or ganciclovir (for Ad.TK transduced cultures). We
quantified the percent of apoptosis by Annexin-7AAD FACS analysis. Finally we transduced E1A-MSC with the Ad.TK or
Ad iC9 vectors and determined the anti-tumor activity of the virus that was produced.
Results
After retroviral transduction, 50-60% of MSCs express E1A, and 60-70% of H1299 cells treated with supernatant from
these E1A MSCs supernatant were GFP+, versus 5% that received supernatant from E1A negative MSCs. Thus, E1A MSC
are able to produce adenovectors that infect tumor cells. Fifty percent of H1299 cells exposed to Ad.iC9 were CD19+, and
the percentage rose to 95% under hypoxic conditions. H1299 exposed to Ad.Tk were 98% GFP positive. Exposure to a
single dose of CID (80nM) killed 65% of hypoxic Ad.iC9 transduced cells versus 12% of normoxic cells, demonstrating
selectivity for hypoxic tumor. Conversely, addition of ganciclovir to normoxic Ad.Tk H1299 cells produced 95%
apoptosis, demonstrating the complementary anti-tumor activity of the two approaches
Conclusion
We were able to generate MSCs that produce adenoviral vectors encoding suicide genes that have specific antitumor
activity both on hypoxic and dividing normoxic lung tumor cells.
Financial Disclosure (Valentina Hoyos)
No
FDA Disclosure
Cleared:Yes
Keywords
Mesenchymal Stromal Cells
Lung cancer
Suicide Gene therapy
None
Abstract ID: 99
Attitudes And Barriers For English And Spanish Promotores/Community Health Workers Educating Cancer
Survivors About Physical Activity
Author List
1. Presenting Author: Deborah Vollmer Dahlke
2. Additional Author: Marcia Ory
3. Additional Author: Jinmyoung Cho
4. Additional Author: Venus Gines
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
In conducting this survey, our team sought to understand Promotores de Salud and Community Health Workers (P/CHW)
attitudes and barriers for educational programming to increase physical activity among older cancer survivors. We also
wanted to understand if there were differences between English vs. Spanish speakers in how P/CHW used social media and
mobile technology in seeking health information.
Methods
Two online surveys were distributed, one in English and one in Spanish, to statewide organizations and individual P/CHW.
Participants were offered both surveys and could select to reply in English or Spanish. After an initial emailing to 150
P/CHW, an additional 137 P/CHW were invited to participate using a snowball methodology. A total of 287 surveys were
emailed with 254 respondents (88.5%) resulting in 168 English language surveys and 86 Spanish language surveys
returned.
Results
(Note: These are preliminary results, additional analyses are underway) When asked if they provided services to older
cancer survivors, 48.5% of the English-speaking PCHW and 60% of the Spanish-speaking P/CHW said they did. When
asked about barriers to physical activity, among Spanish speaking P/CHW, 65% said lack of transportation; 52% identified
lack of groups offering programs for older adults to engage in PA; 49% said costs to participate, and 41% said lack of safe
places to walk. Barriers reported among English-speaking P/CHW included costs to participate 39%; lack of safe places to
walk outside, 23.8%; lack of public transportation, 23.8%. The concern that physical activity is harmful for cancer
survivors was cited as a barrier by 15.5% of English-speaking P/CHW as compared to 27.9% of Spanish-speaking P/CHW.
When asked about accessing information on the Internet, 39.5% of the Spanish-speaking P/CHW and 53.6% of the
English-speaking P/CHW said they mobile phones to access the Internet. Both groups expressed a positive interest in
receiving training to educate their older cancer survivor clients about the benefits of physical activity, with 83.3% of
English-speaking and 91.9% of the Spanish-speaking respondents expressing an interest in such training.
Conclusion
This survey, offered in both English and Spanish, suggests significant opportunities exist for providing P/CHW training in
educating older cancer survivors about the benefits of physical activity. Perceptions of barriers to access for engaging in
physical activity vary across the two groups and should be taken into account in developing training that is culturally
appropriate.
Financial Disclosure (Deborah Vollmer Dahlke)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 100
Identification And Validation Of Novel Drug Targets For The Eradication Of KRAS-independent Pancreatic Stem
Cells
Author List
1. Presenting Author: Nora Sanchez
2. Additional Author: Hoaqing Ying
3. Additional Author: Giulio Draetta
4. Additional Author: Andrea Viale
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 01:50 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Pancreatic Ductal Adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths in the U.S. An in-depth
understanding of the signaling mechanisms in PDAC is needed to allow the rational development of effective targeted
therapies. We have developed an in vivo functional genetic screening platform that takes into account the importance of
genetic context and microenvironment to systematically investigate the tumorigenic potential of driver genetic-elements of
interest (GEOI) in PDAC. Using a unique doxycycline (DOX) inducible KrasG12D driven PDAC mouse model (iKras) we
have identified a population of tumor cells that survive KRAS extinction in vivo and in vitro and is highly tumorigenic
upon re-expression of oncogenic KRAS. These cells behave like bona fide stem cells, are intrinsically more resistant to
drugs and environmental stresses, suggesting an important role in drug resistance and tumor relapse after conventional
therapies.
Methods
We have developed an inducible KRAS* mouse model of PDAC that enables pancreas-specific and doxycycline-inducible
expression of KrasG12D in a p53 mutant background (p53L/L or L/+)(Ying et al 2012). Using this mouse model we
demonstrated that oncogene expression is dispensable for a small subpopulation of tumor cells. Cells surviving KRAS
extinction were extensively characterized including stem cell profile, tumorigenic potential and genome wide transcriptome
analysis.
Results
The ability of these cells to form tumors in vivo or spheres in serum free culture is dependent on expression of KRAS.
Upon oncogene extinction, the majority of the cells undergo apoptosis. The few surviving cells express CD133, remain
quiescent for an extended period of time, and are highly enriched in tumor initiating cells as determined by limiting
dilution assay when re-transplanted in mice. Upon oncogene induction they can reform tumors and spheres. Transcriptional
analysis reveals ~ 600 genes specifically regulated in surviving cells.
Conclusion
The unique characteristics of the surviving cells have provided a system we can exploit to identify GEOIs that cooperate
with K-RAS in promoting PDAC. Enrichment of genes in these highly tumorigenic cells provide a refined set of relevant
GEOIs that we are now interrogating in a high-throughput fashion using a pooled virus, gain or loss of function approach
in vivo. Resulting hits can then be individually validated in mouse and human spheroid assays. We anticipate this powerful
screening approach will identify several potential druggable targets in PDAC.
Financial Disclosure (Nora Sanchez)
No
FDA Disclosure
Cleared:Yes
Keywords
pancreatic cancer
stem cells
gain of function screen
None
Abstract ID: 101
Transparency And Public Trust In Cancer Genomics
Author List
1. Presenting Author: Stacey Pereira
2. Additional Author: Amy McGuire
3. Additional Author: Whitney Davidson
4. Additional Author: Lauren Becnel
5. Additional Author: Richard Gibbs
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Community engagement is necessary to realizing the current goals of cancer genome research. As such, there is a need for
greater transparency in research endeavors that promotes public trust and involvement from the community.
Methods
We have built transparency into the study design for the Texas Cancer Research Biobank (TCRB) in three ways: through
our public webpage, our annotated informed consent document, and our active governance structure.
Results
1) Our public webpage makes TCRB information and news readily available to the public. The webpage includes an
overview of the TCRB project, lay descriptions of ongoing research being done with TCRB samples, a link to the informed
consent document for the project, information on key personnel, and contact information. 2) Our informed consent
document was developed using best practice models and input from leaders in the field and explains in detail how
biological samples are used and the risks related to genomic research in order to ensure that participants are fully informed.
We also created an annotated version of the informed consent document that reviews the relevant literature and describes
the rationale for each section of the consent. These documents are publicly available both on our TCRB webpage and on
the National Human Genome Research Instituteâ€™s (NHGRI) webpage. 3) Our governance structure, the Resource
Access Committee for the TCRB, comprises a broad representation of members, including a bioethicist, a biostatistician,
members from all TCRB contributing sites, other scientific experts outside the TCRB, and a community member. The
Committee applies a standard review policy to all sample and data requests that focuses on the scientific merit and
potential impact of the proposed research project, as well as any potential ethical issues to ensure the best possible use of
resources. In accordance with our commitment to transparency, the Committeeâ€™s policies and procedures are available
to the public on our webpage.
Conclusion
By building transparency into several aspects of the TCRB, we seek to promote public trust and engagement with the
community.
Financial Disclosure (Stacey Pereira)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 102
An Essential Non-cell Autonomous Role For The miR-143/145 Cluster In Epithelial Regeneration In The Colon
Author List
1. Presenting Author: Guanglu Shi
2. Additional Author: Raghu Chivukula
3. Additional Author: Joshua Mendell
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Over the past decade, numerous profiling experiments have established that dysregulation of microRNAs (miRNAs) is a
hallmark of cancer cells. The co-transcribed miRNAs miR-143 and miR-145 are frequently dysregulated in cancer and
their downregulation has been repeatedly reported in colon cancer and other solid tumors of epithelial origin. Furthermore,
overexpression of miR-143/145 inhibits cell proliferation and tumor growth, suggesting that these miRNAs function as
cell-autonomous tumor suppressors. Yet the consequences of loss-of-function of miR-143/145 on tumorigenesis in
vivo have not been evaluated and the physiologic roles of miR-143/145 in epithelial tissues are poorly understood.
Methods
To address these questions, we generated a conditional knockout mouse line in which the miR-143/145 locus, flanked by
LoxP sites, could be deleted somatically or in the germ line.
Results
Germline deletion of miR-143/145 did not result in any overt abnormalities in the development or baseline function of
epithelial tissues including the colon. To determine whether a latent defect might be revealed under stress conditions, we
subjected miR-143/145-/- mice to dextran sulfate sodium (DSS) treatment, which induces an epithelial
injury-repair sequence in the colon that is well tolerated in wild-type mice. Unexpectedly, miR-143/145-/-
mice failed to regenerate colonic epithelium after DSS and rapidly succumbed. To elucidate the cellular mechanism
underlying this defect, we first examined miR-143/145 expression by in situ hybridization and qPCR in
purified cell populations from the colon. Surprisingly, these studies revealed that miR-143/145 were undetectable in the
epithelial compartment of the intestine yet were abundantly expressed in smooth muscle and other mesenchymal cells.
Consistent with these findings, pan-mesenchymal deletion of miR-143/145 (using Twist2-Cre) or smooth muscle-specific
deletion (using SMMHC-Cre) resulted in impaired injury response whereas regeneration was normal following epithelial
knockout (using Villin-Cre).
Conclusion
These results document that, contrary to the prevailing view, miR-143/145 are not intrinsic regulators of epithelial
proliferation in the colon. Furthermore, their lack of expression in epithelium argues strongly against a cell-autonomous
tumor suppressor role for these miRNAs in colon cancer. Additionally, these findings reveal an essential and previously
undocumented role for intestinal smooth muscle in coordinating epithelial regeneration. Ongoing experiments aim to
elucidate the molecular nature of this smooth muscle-epithelial paracrine signaling axis and the mechanisms through which
it is regulated by miR-143/145.
Financial Disclosure (Guanglu Shi)
No
FDA Disclosure
Cleared:Yes
Keywords
microRNA
colon
miR-143/145
None
Abstract ID: 103
Impact Of Comprehensive Tobacco Prevention And Control Coalitions On State-funded Telephone Cessation
Counseling Quitlines: The Texas Experience
Author List
1. Presenting Author: Barry Sharp
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
In 2008, the Texas Department of State Health Services began funding six coalitions around the state to provide
comprehensive tobacco prevention and control activities based on best practice guidelines from the Centers for Disease
Control and Prevention. In addition, these coalitions were supported by state purchased media campaigns to support
tobacco cessation and promote the stateâ€™s telephone quitline. When compared to communities who received only
cessation media or no intervention, communities where local coalitions are active in comprehensive tobacco prevention and
control activities show a dramatically higher rate of calls for cessation services from the stateâ€™s telephone quitline that
has increased over time.
Methods
Telephone quitline services are provided by Alere Wellbeing, Inc., under contract with the DSHS, and provides monthly
reports containing caller demographics and services provided. Caller data is tracked on a monthly basis and is
geographically divided by counties which have DSHS funded comprehensive tobacco prevention and control coalitions
(n=15), counties which share media markets with the coalitions but do not have coalitions (n=88), and areas which receive
neither funded coalitions or media messages supporting cessation (n=151). Call volume was compared across the three
geographic spectrums and analyzed at a per county and per 1,000 residents in order to compare urban, rural and frontier
areas of the state.
Results
While the gross call volume was greatest in the counties with no interventions due to having nearly 10 times the number of
counties as the coalition areas, the coalition counties produced nearly eleven times the number of calls per county on a
monthly basis than the unfunded counties. Coalition counties averaged 22.18 calls per county per month while counties
with no interventions averaged 2.38. Counties that received media only reported an average of 2.61 calls per county per
month. The difference between coalitions areas other the other two areas was only five-times in 2008 and has steadily
increased since then.
Conclusion
The increased number of calls relates to an increased number of individuals who are quitting tobacco, thus creating a
long-term benefit to the community through reduced demand for health care services (and the associated costs) and
increased productivity. The synergy of local activities around prevention to tobacco initiation, promoting cessation and
reducing exposure to secondhand smoke change the social norms within the community and inspire tobacco users thinking
about quitting to make the decision to take action.
Financial Disclosure (Barry Sharp)
No
FDA Disclosure
Cleared:Yes
Keywords
Tobacco
Smoking
Cessation
Coalitions
Abstract ID: 104
Prostate MRI: Access to and Current Practice of Prostate MRI In Texas and Compared to the United States
Author List
1. Presenting Author: Rulon Hardman
2. Additional Author: James Leake
3. Additional Author: Vijayanadh Ojili
4. Additional Author: Alampady Shanbhogue
5. Additional Author: Ian Thompson
6. Additional Author: Javier Hernandez
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Indications for prostate MRI are expanding and this procedure is gaining increasing acceptance in clinical practices. Some
groups advocate the use of prostate MRI in active surveillance and cancer therapy planning. However, prostate MRI must
be performed at a certain quality to accurately detect and stage cancer. This study was conducted to determine the current
access, MRI imaging protocols, and common indications for prostate MRI in Texas among the various practice models.
Methods
A brief survey was sent via the Texas Radiological Society email lists to practicing radiologists. Results are compared
using descriptive statistics. Results were compared to responses from the United States.
Results
Four academic groups, two large private practice and seven community groups responded to the survey. 75% of academic
groups, 100% of the large private practice groups which responded, and 14% of community groups perform prostate MRI.
Academic groups perform prostate MRI at 3.0T with or without endorectal coil. All of the non-academic groups performed
prostate MRI at 1.5T without endorectal coil. All groups perform anatomic T1 and T2 weighted images and an additional
â€œfunctionalâ€• sequence. Academic groups perform both DCE and DWI images while non-academic groups perform
only one of these sequences. Only one center in Texas is able to perform MRI directed biopsy.
Conclusion
Prostate MRI is a commonly performed examination at academic institutions. Areas for improvement include educating
community and private practice groups as to the need to perform high-quality MRI techniques and improving the access to
MRI directed biopsy in institutions performing prostate MRI.
Financial Disclosure (Rulon Hardman)
No
FDA Disclosure
Cleared:Yes
Keywords
MRI
prostate cancer
active surveillance
cancer treatment
Abstract ID: 105
Post-treatment Surveillance In Locoregional Breast Cancer: Guideline Adherence And Patterns In Use Of
Non-recommended Testing
Author List
1. Presenting Author: Abhishek Parmar
2. Additional Author: Kristin Sheffield
3. Additional Author: Gabriela Vargas
4. Additional Author: Yimei Han
5. Additional Author: Celia Chao
6. Additional Author: Taylor Riall
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 02:40 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Figure1_CPRIT.JPG
Summary
Introduction
Annual mammography and physical exam are currently recommended for the post-treatment surveillance of early stage
breast cancer. The current utility of new and non-recommended tests such as dedicated breast MRI, computed tomography
(CT) or magnetic resonance imaging (MRI) of the head, chest, and abdomen, or positron emission tomography (PET) is
unknown. OBJECTIVE: To use population-based data to describe current trends in use of recommended and
non-recommended tests as surveillance modalities in older women following definitive operation for breast cancer.
Methods
We used Texas Cancer Registry-Medicare linked data (2001-2007) to identify physician visits, mammography, MRI, CT,
and PET CT scans in patients 66 and older with ductal carcinoma-in-situ (DCIS) and stage I-III ductal breast cancer who
underwent curative-intent surgery. Time trends in the use of recommended and non-recommended tests were assessed.
Tests were considered surveillance tests if patients had no symptoms of metastatic disease in the 3 months prior to a given
study.
Results
We identified 8,598 patients with resected DCIS (37.3%) or stage I-III breast cancer (62.7%). 58.7% underwent
breast-conserving therapy and 41.3% underwent mastectomy. Adherence to guidelines is comparable to previous
population-based studies, with 78.9% of patients undergoing postoperative mammography and 98.8% seeing a physician in
the two years after initial surgical therapy. Mammography use decreased from 81.0% diagnosed in 2001 to 75.2%
diagnosed in 2007 (P<0.0001). There was a concomitant increase in the use of breast MRI from 0.5% to 7.0% (P<0.0001).
Within 2 years of surgery, 31.9% of patients underwent abdominal CT/MRI, 26.5% underwent chest CT/MRI, 22.6%
underwent head CT/MRI, 26.0% underwent bone scan, 8.3% underwent PET/PET CT, and 95.2% underwent LFTs for
surveillance. Non-recommended tests were used most often in patients with regional disease, but also frequently done in
patients with DCIS, ranging from 3.2% for PET/PET CT to 22.0% for abdominal CT/MRI. For all studies except bone
scans, use increased over the time period, with PET/PET-CT increasing from 1.5% to 12.4%. When stratified by stage, the
same increasing patterns in use were observed; these time trends in testing are shown in Figure 1.
Conclusion
While adherence to evidence-based guidelines has been appropriate, the use of non-recommended tests has increased over
the study period. Use of intensive surveillance testing in asymptomatic patients with DCIS and the increasing trends in use
of new tests imply overuse. Further studies are needed to assess the comparative benefit and/or harm of intensive
surveillance with CT, MRI, and PET/PET-CT.
Financial Disclosure (Abhishek Parmar)
No
FDA Disclosure
Cleared:Yes
Keywords
breast cancer
surveillance
recurrence
metastasis
Abstract ID: 106
Functionally Prioritizing Somatic Driver Aberrations In Cancer
Author List
1. Additional Author: Turgut Dogruluk
2. Additional Author: Yiu-Huen Tsang
3. Additional Author: Ping Wu
4. Additional Author: Armel Gifford
5. Additional Author: Nikitha Nair
6. Presenting Author: Kenneth Scott
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 02:40 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
pdac in vivo screen outline.jpg
Summary
Introduction
The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) are cataloging genomic
aberrations across major tumor lineages. These efforts are revealing an extraordinary level of genome complexity made up
of not only key â€œdriverâ€• events critical to pathogenesis, but also numerous biologically-neutral â€œpassengersâ€•
inherent to unstable tumor genomes. The challenge now is to find ways to identify functional driver aberrations, as
targeting such events or their activated pathways has great potential for improving patient outcomes. Efficient driver
identification requires robust pipelines to prioritize the thousands of putative targets emerging from genomics studies.
However, little progress has been made toward developing gain-of-function systems for validating overexpressed or
activated oncogenes.
Methods
We have assembled a platform of ~32,000 sequence-verified open reading frames (ORFs, hereafter termed â€œgenesâ€•)
for which we have devised high-throughput strategies permitting their introduction into â€œtargetâ€• cells for screen-based
assays. We have integrated these reagents into infrastructure enabling high-content genetic screens to accelerate functional
validation of somatic aberrations driving cancer. This work is made possible through several technological advances made
in our laboratory that include (1) robotics driven, high-throughput modeling of somatic mutations in a manner that permits
construction of every somatic aberration found within a given candidate cancer gene and (2) a novel molecular barcoding
approach that facilitates cost-effective detection of driver events following in vitro and in vivo pooled functional screens.
Results
An important feature of our system is that target cells, once infected with a gene library, can be entered into parallel
screens to maximize discovery potential (e.g., screens for driver addiction, cell invasion, anchorage-independent growth,
drug resistance, etc.). While cell-based screening systems are tractable, in vitro models do not fully recapitulate all
hallmarks of tumorigenesis and metastasis. To address this challenge, we have also developed in vivo screening models
that leverage barcode sequencing technology to identify drivers positively selected within tumors and metastases. In
addition to our CPRIT-funded project aimed at identifying driver aberrations in pancreas cancer, we recently embarked on
a large collaborative project funded by the NIH Cancer Target Discovery and Development Network aimed at leveraging
these tools and TCGA data to identify new targets across a variety of cancer types.
Conclusion
We are employing our novel screening platform to discover functionally important cancer genes identified by cancer
sequencing efforts. Our â€œprioritization pipelineâ€• will provide the cancer research community information on the most
promising somatic aberrations for downstream biomarker and drug development.
Financial Disclosure (Kenneth Scott)
No
FDA Disclosure
Cleared:Yes
Keywords
Genetic screen
Pancreas cancer
TCGA
Somatic mutations
Abstract ID: 107
Extracellular Matrix Compliance Stimulates Estrogen Output In Adipose Stromal Cells Through A
DDR1-Dependent Mechanotransduction Mechanism
Author List
1. Additional Author: Sagar Ghosh
2. Additional Author: Keith Ashcraft
3. Additional Author: Yanfen Hu
4. Presenting Author: Rong Li
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Slide1.jpg
Summary
Introduction
Adipose stromal cells (ASCs) are the primary source for estrogen synthesis in adipose tissue. Aberrant adipose estrogen
production is linked with several hormone-dependent pathologies including breast cancer. Here we show that the
mechanical phenotype of the tissue, as determined by extracellular matrix (ECM) and cytoskeletal dynamics, is critical for
ASC endocrine output.
Methods
Using either synthetic ECMs or elastomeric micropost arrays with tunable rigidity, we find that increasing ECM
compliance significantly induces transcription of aromatase, a rate-limiting enzyme in estrogen biosynthesis.
Results
This ECM-initiated mechanical cue is sensed at the cell surface by DDR1, which in turn triggers JNK-mediated
phosphorylation of transcription factor JunB. Phospho-JunB binds to and stimulates two tissue-specific aromatase
promoters that are known to be hyperactive in breast cancer. In contrast, elevated ECM stiffness results in actin stress fiber
formation within ASCs, which antagonizes aromatase transcription. Functionally, ECM-stimulated stromal estrogen
production enhances estrogen-dependent transcription within breast cancer cells and promotes their growth in a stromal
DDR1-dependent manner.
Conclusion
Our work uncovers a mechanotransduction mechanism that converts biomechanical signals to adipose hormone output.
Financial Disclosure (Rong Li)
No
FDA Disclosure
Cleared:Yes
Keywords
adipose stromal cells
extracellular matrix compliance
estrogen synthesis
obesity-associated breast cancer risk
Abstract ID: 108
Inhibitory Receptors Support Normal And Leukemia Stem Cells
Author List
1. Presenting Author: Chengcheng Zhang
2. Additional Author: Junke Zheng
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
How environmental cues regulate adult stem cell and cancer cell activity through surface receptors is
poorly understood. Angiopoietin-like proteins (ANGPTLs), a family of seven secreted glycoproteins, are known to support
the activity of haematopoietic stem cells (HSCs) in vitro and in vivo. ANGPTLs also have important roles in lipid
metabolism, angiogenesis and inflammation, but were considered 'orphan ligands' because no receptors were identified.
Methods
color: rgb(0, 0, 0); ">We used a number of methods including expression cloning and candidate screening to attempt to
identify receptors for ANGPTLs. Flow cytometry, Co-IP, Biacore, and liquid-phase equilibrium binding assays were used
to characterize the ligand-receptor binding. Bone marrow reconstitution analysis, CFU assay, flow cytometry analysis,
cytospin, immunohistochemistry, and transplanttaion were used to measure hematopoietic stem cell activity and leukemia
development.
Results
color: rgb(0, 0, 0); ">We show that the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor B2
(LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB) are receptors for several ANGPTLs.
LILRB2 and PIRB are expressed on human and mouse HSCs, respectively, and the binding of ANGPTLs to these
receptors supported ex vivo expansion of HSCs. In mouse transplantation acute myeloid leukaemia models, a deficiency in
intracellular signalling of PIRB resulted in increased differentiation of leukaemia cells, revealing that PIRB supports
leukaemia development.
Conclusion
color: rgb(0, 0, 0); ">Our study indicates an unexpected functional significance of classical immune-inhibitory receptors in
maintenance of stemness of normal adult stem cells and in support of cancer development.
Financial Disclosure (Chengcheng Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
leukemia
receptor
stem cells
signal transduction
Abstract ID: 109
Using Qualitative Methods To Identify Effective Communication Strategies Between LIVESTRONG Promotores
And Latino Cancer Survivors In Central Texas
Author List
1. Presenting Author: Sarah Arvey
2. Additional Author: C. Emily Hendrick
3. Additional Author: Haley Justice Gardiner
4. Additional Author: Gema Lane
5. Additional Author: Ruth Rechis
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The challenges of cancer survivorship combined with the barriers many Latinos face to timely and quality health care
access in Texas (e.g. language barriers, lack of health insurance, some cultural beliefs and practices related to health and
disease) call for identification of effective methods for meeting the needs of medically underserved Latino cancer
survivors. Through the LIVESTRONG (LS) Promotores Program, promotores (community health workers who work with
Latinos) are trained to provide basic information about cancer survivorship and LS cancer navigation services. Once
trained, promotores employ the information and skills gained in the training in their communities, yet, as with many
community health worker (CHW) programs, little is understood as to what the “active ingredients” are in
promotor/survivor interactions that result in improved outcomes among Latino cancer survivors. Thus, investigators
utilized a combination of qualitative methods to explore and evaluate this program.
Methods
Using ethnographic methods, investigators conducted semi-structured, open-ended interviews with LS promotores,
survivors, and LS navigators in Central and South Texas. Additionally, through direct observation, investigators observed
promotores as they interacted with survivors in various settings including health fairs, survivors’ homes, and cancer
care clinics. Field notes were recorded and interviews conducted in Spanish and English were transcribed. Demographic
and acculturation data was collected from promotores and survivors. Data was analyzed and triangulated through two
methods: 1) Two investigators, one involved in data collection and one not, conducted qualitative content analysis of
transcripts using NVivo v9 software to identify emergent themes. 2) After initial analyses were completed, focus groups
were held with representatives from each study population to verify findings.
Results
Using qualitative methods to collect data from three different perspectives of the program (promotores, survivors and
navigators) helped to create a nuanced, well-rounded picture of the promotor/survivor interaction. Collecting multiple
perspectives on the same topic served to triangulate and verify findings. Further, verifying the findings from both an
outsider (investigator) and insider (program participant) perspective increased the validity of study findings.
Conclusion
When exploring the “active ingredients” of CHW programs focused on a specific population with unique
cultural attributes that contribute to health outcomes, qualitative methods that focus on collecting and analyzing study data
from a variety of perspectives and via different collection techniques can increase validity and robustness of findings.
Financial Disclosure (Sarah Arvey)
No
FDA Disclosure
Cleared:Yes
Keywords
community health workers
promotores
survivorship
education
Abstract ID: 110
HOXA1 Drives Melanoma Tumor Growth And Metastasis And Elicits An Invasive Gene Expression Signature
That Prognosticates Clinical Outcome
Author List
1. Presenting Author: Joanna Wardwell-Ozgo
2. Additional Author: Turgut Dogruluk
4. Additional Author: Yiqun Zhang
5. Additional Author: Remco Van Doorn
6. Additional Author: Chad Creighton
7. Additional Author: Lynda Chin
8. Additional Author: Kenneth Scott
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Metastatic melanoma is a highly lethal disease that is notorious for its aggressive metastatic course and eventual resistance
to existing therapies. Currently we possess a limited understanding of the genetic events driving progression of melanoma,
particularly those responsible for its metastatic propensity, and much effort is focused on identifying pro-metastatic
genetics aberrations or perturbed signaling networks that constitute new therapeutic targets. We recently reported an
oncogenomics-guided screening approach designed to identify genetic drivers of early-stage melanoma metastasis.
Methods
We functionally validated and assessed the mechanism by which homeobox transcription factor A1 (HOXA1),
the top-scoring enhancer of cell invasion identified by our previous study, contributed to melanoma progression by
numerous in vivo and in vitro biochemical and genetic assays.
Results
Transcriptome and pathway profiling analyses of cells expressing HOXA1 revealed up-regulation of factors
involved in diverse cytokine pathways that include the TGFÎ² signaling axis, which we further demonstrated to be required
for HOXA1-mediated cell invasion. Transcriptome profiling also showed HOXA1â€™s ability to
potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes
required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression
de-differentiates cells into a pro-invasive cell state concomitant with TGFÎ² activation. Our analysis of publicly available
datasets indicated that the HOXA1-induced gene signature successfully categorizes melanoma specimens
based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on
expression in primary tumors. We have identified putative HOXA1 effector genes by defining the
HOXA1 â€œtargetomeâ€• via an integrated analysis of HOXA1 transcriptome and ChIP-SEQ
datasets, and we are leveraging our collection of ~32,000 sequence-verified cDNA clones and molecular barcoding
technologies to conduct in vivo genetic screens to identify genes responsible for
HOXA1-mediated tumorigenesis and metastasis.
Conclusion
Together, these validation data and mechanistic insights suggest that patients whose primary tumors express
HOXA1 are among a high-risk metastasis subgroup that should be considered for anti-TGFÎ² therapy in
adjuvant settings. Moreover, the further analysis of HOXA1 target genes in melanoma may reveal new
pathways or targets amenable to therapeutic intervention.
Financial Disclosure (Joanna Wardwell-Ozgo)
No
FDA Disclosure
Cleared:Yes
Keywords
HOXA1
melanoma
metastasis
TGFb
Abstract ID: 111
AP-1 As A Key Mediator Of Endocrine Resistance In Breast Cancer.
Author List
1. Presenting Author: Mario Giuliano
2. Additional Author: Malorni Luca
4. Additional Author: Mathieu Lupien
5. Additional Author: Abhijit Mazumdar
6. Additional Author: Gary Chamness
7. Additional Author: Rinath Jeselsohn
8. Additional Author: Hansen He
9. Additional Author: Myles Brown
10. Additional Author: Powel Brown
11. Additional Author: C. Kent Osborne
12. Additional Author: Rachel Schiff
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The transcription factor AP-1 is a key regulator of cell growth and survival, and a downstream component of several
pathways deregulated in endocrine-resistant breast cancer (BC), such as epidermal growth factor receptor (EGFR)
signaling. In our preliminary studies, we found that AP-1 inhibition by inducible expression of dominant-negative (DN)
c-Jun sensitizes MCF7 cells to endocrine treatment and reverses resistance in vitro and in vivo. Recent studies of estrogen
receptor (ER) genomic cistromes (genome-wide ER binding sites) suggest that estrogen-independent/ EGF-mediated
activation of MCF7 cells leads to a substantial enrichment of AP-1 regulatory elements in ER DNA-binding sites. Our
overall goals are to better understand the molecular features by which AP-1 modulates ERâ€™s transcriptional program in
the context of endocrine resistance, and to validate AP-1â€™s role in endocrine resistance across diverse ER+ pre-clinical
models.
Methods
Bioinformatic analyses were performed to intersect our previously described MCF7 xenograft/Tam-resistant gene signature
with the datasets of genes associated with ER DNA-binding sites obtained by whole-genome ER cistromic analysis under
estrogen or EGF stimulation of MCF7 cells. An inducible lentiviral system will be used to modulate AP-1 activity in the
preclinical models.
Results
We computed genes localized within 20 kilobases up/downstream of the EGF-unique ER DNA-binding sites (i.e., sites
induced exclusively by EGF- and not by estrogen). This gene list was significantly enriched in our Tam-resistant
signature. Remarkably, 90% of the DNA binding sites associated with the overlapping genes harbored an AP-1 motif.
Additionally, pathway analysis of the Tam-resistant upregulated and overlapping genes identified major signaling
pathways known to be associated with endocrine resistance, including HER2, ERK, JNK, p38 MAPK, PKC, and PI3K.
Using the pINDUCER lentiviral system, we will test whether AP-1 inhibition prevents or reverses endocrine resistance in
multiple pre-clinical models, recapitulating the clinical heterogeneity of BC. ER and AP-1 transcriptional and cistromic
profiles will then be established in the three endocrine-resistant models showing the highest dependency on AP-1
activation, in order to gain further insights into AP-1â€™s role in endocrine resistance, and to identify new molecular
targets.
Conclusion
Overall, our results suggest that AP-1 may be a new hallmark of endocrine resistance by mediating the signaling of various
upstream pathways involved in this resistance. The AP-1-related genetic signatures that we will derive from our study will
lay the foundation for future development of clinical biomarkers and novel pharmacological targets to improve prediction
of endocrine resistance and enhance or restore endocrine sensitivity.
Financial Disclosure (Mario Giuliano)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer
Endocrine Resistance
AP-1
Cistromic analysis
Abstract ID: 112
Rapid Disease Identification And Drug Susceptibility Screening By Microwell Assay
Author List
1. Presenting Author: Yen Nguyen
2. Additional Author: Lidong Qin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
To meet the global needs of point-of-care (POC) devices, a microwell device was developed as a multifunctional assay for
disease diagnostics and drug susceptibility testing.
Methods
The device integrates on-chip cell culturing, immunoassay, and high-resolution fluorescent imaging. Our current study
integrates ELISA techniques into a microfluidic device that can isolate and detect single cells of unprocessed biological
samples (i.e. blood, sputum, or urine). Samples, as small as a few microliters, can be injected into our device for single cell
analysis.
Results
As a result, the microwell device detected antigens released from single cells within 24-48-hour culture. Susceptible
drug-treated cells showed significant decreased in antigen production, while no change was observed when treated with
resistant drugs.
Conclusion
The combination of microwell technology and ELISA assay holds potential to the development of a rapid, sensitive, and
specific diagnostics and susceptibility testing of diseases.
Financial Disclosure (Yen Nguyen)
No
FDA Disclosure
Cleared:Yes
Keywords
DIAGNOSTICS
ELISA
MICROFLUIDICS
POINT OF CARE
Abstract ID: 113
Bridging Access To Breast Healthcare Services
Author List
1. Presenting Author: Erika Cuellar
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The purpose of the Bridging Access to Breast Healthcare Services project is to reduce breast cancer disparities among
minority and medically underserved women by increasing screening mammography in Northern Texas, with a focus on
Dallas and the surrounding Southern and Eastern rural counties. The project will serve 3400 women over two years.
Methods
The project plans to: 1) increase mammography screenings using the Mobile Mammography unit from Methodist Medical
Center of Dallas to reduce structural and geographical barriers to care by providing free mammography services to women
in rural and underserved areas; 2) increase community partnerships in the Eastern/ Southern counties of North Texas to
identify medically underserved population groups and area; 3) conduct education sessions about breast health awareness
and the availability of free mammography services utilizing age, language and culturally appropriate materials; 4) provide
diagnostic care and patient navigation services through treatment for women with abnormal findings.
Results
The Bridge Breast Network served 2,100 in year one of the grant as a result of CPRITâ€™s support. In addition, over 48%
of the women who received a screening or diagnostic mammogram in year 1 were between the ages of 40 and 50, while
60% of the women who received a screening or diagnostic mammogram reported never having received one before.
Seventy-five percent of the 45 positive cancer diagnosis found in year were at stage 1 or stage 2. We have also been
successful in year one by creating 14 new partnerships with organizations such as Texas AgriLife, Lake Pointe Medical
Center and Texas Health Department of Lamar County.
Conclusion
Year 1 data demonstrates the Bridge Breast Network is meeting its goals of expanding screening and diagnostic services to
women residing in rural counties in North Texas as well as increasing the number of minority women who are receiving
first time mammograms.
Financial Disclosure (Erika Cuellar)
No
FDA Disclosure
Cleared:Yes
Keywords
Rural Counties
Screening mammograms
North Texas
underserved
Abstract ID: 115
Inhibition Of PELP1 Oncogenic Functions With Cell Permeable Peptides
Author List
1. Presenting Author: Monica Mann
2. Additional Author: Ratna Vadlamudi
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Estrogen receptor (ERÎ±) is the fundamental transcription factor in breast cancer progression. Therapies targeting ERÎ± are
effective; however, many patients ultimately develop resistance and recur as metastases. ERÎ± signaling is mediated by
coregulator proteins that can have altered expression and/or function that promotes therapy resistance and metastasis by
enhancing hormone-independent ERÎ± signaling that involve epigenetic changes. An alternative strategy for inhibiting
ERÎ± signaling in therapy resistant and metastatic tumors is to inhibit the function of ERÎ± coregulators. PELP1 is an ERÎ±
coactivator and proto-oncogene which is overexpressed in breast cancer, promotes breast cancer progression by epigenetic
changes at ERÎ± target genes and is an independent marker of poor prognosis and breast cancer survival. The objective of
this study is to develop an inhibitor of PELP1-mediated ERÎ± coactivator functions.
Methods
Since PELP1 lacks any known enzymatic activity, we targeted PELP1 protein-protein interactions to inhibit its oncogenic
functions. We used a yeast two-hybrid system to screen a library of random peptides (~10-7) fused to a
transcriptional activation domain and identified 23 peptides with high affinity for PELP1. We then used fluorescent
microscopy, co-immunoprecipitation, proliferation and migration assays to determine the effect of the peptides on PELP1
oncogenic functions.
Results
Two of the PELP1-inhibiting peptides (PIP1 and PIP2) significantly block PELP1 coactivator functions. We used a
TAT-peptide fusion of PIPs to deliver the peptides into cells, confirmed cellular uptake of the TAT- PIPs by fluorescent
microscopy and confirmed PELP1-PIP binding by biotin-avidin peptide pull-down assays. Both PIP1 and -2 significantly
inhibited PELP1-mediated proliferation in two ERÎ±-positive breast cancer cells. A GenBank search revealed homology of
PIPs with the methyltransferase G9a (Bat8/KMT1C/EHMT2) that is commonly overexpressed in aggressive breast cancer,
contributes to epigenetic silencing of tumor suppressors and promotes cancer invasion and metastasis. In vivo
co-immunoprecipitation analysis and an in vitro binding assay confirmed PELP1 interaction with G9a, and
peptide competition assays indicated that the TAT-fused peptides could interrupt PELP1-G9a interaction. Both PIP1 and -2
substantially inhibited PELP1-mediated cell invasion/migration in Boyden chamber assays. Interestingly, disrupting
PELP1-G9a interaction with PIPs sensitized resistant cells to hormonal therapy. Mechanistic studies revealed that
PELP1-G9a interactions play a critical role in epigenetic changes in therapy resistant cells.
Conclusion
Our studies identified a novel inhibitor of PELP1 that can be used for therapeutic targeting of ERÎ±-coregulator driven
cancer progression and therapy resistance.
Financial Disclosure (Monica Mann)
No
FDA Disclosure
Cleared:Yes
Keywords
PELP1
Breast Cancer
Peptide Inhibitor
Estrogen Receptor
Abstract ID: 116
Imaging Shows Breast Cancer-related Lymphedema Is A Systemic Disease
Author List
1. Presenting Author: Melissa Aldrich
2. Additional Author: John Rasmussen
3. Additional Author: I-Chih Tan
4. Additional Author: Renie Guilliod
5. Additional Author: Caroline Fife
6. Additional Author: Erik Maus
7. Additional Author: Latisha Smith
8. Additional Author: Eva Sevick-Muraca
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
CPRIT pic2.jpg
Summary
Introduction
As cancer treatments improve, the number of cancer survivors continues to increase. A serious survivorship concern is the
development of lymphedema, a debilitating, disfiguring disease that develops in ~40% of breast cancer survivors, and in
significant percentages of survivors of other cancers. Current treatment of breast cancer-related lymphedema (BCRL) is
only directed to the affilicted arm. Near-infrared fluorescent (NIRF) imaging of arm lymphatic vessel architecture and
function in BCRL and control subjects revealed a trend of increased abnormalities in both afflicted and the clinically
"normal" arms. These results suggest that BCRL is a systemic disease worthy of bilateral limb and truncal basin treatment.
These data also suggest that NIRF can be used to detect early changes in lymphatics. Early treatment of lymphedema has
proven to reverse/prevent chronic lymphedema development, so NIRF imaging of lymphatics may reduce the suffering and
worry of development of lymphedema in cancer survivors.
Methods
Arm and axillary lymphatics of BCRL and control subjects were imaged using a custom-built near-infrared imaging system
and microdose levels of indocyanine green (ICG), a fluorescent dye. BCRL subjects were classified into three groups: (a)
6 months or less, (b) between 1 and 2 years, and (c) greater than 5 years since onset of BCRL symptoms.
Results
Percentages of lymphatic abnormalities increased with increasing time since BCRL onset on both the afflicted and
"normal" sides.
Conclusion
Lymphedema is a systemic, not unilateral, disease. These results provide impetus for early, aggressive, systemic detection
and treatment of post-cancer lymphedema.
Financial Disclosure (Melissa Aldrich)
No
FDA Disclosure
Cleared:Yes
Keywords
lymphedema
breast cancer-related lymphedema
near-infrared fluorescence imaging
lymph
Abstract ID: 117
Integrated Genomic Characterization Of Oral Cavity Squamous Cell Carcinoma Identifies Frequent Genomic
Drivers
Author List
1. Presenting Author: Curtis Pickering
2. Additional Author: David Wheeler
3. Additional Author: Jeffrey Myers
4. Additional Author: Mitchell Frederick
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Head and neck cancer includes a diverse group of tumors from the upper aerodigestive tract. Oral cavity squamous cell
carcinoma (OSCC) is one subsite of this disease with a five-year survival of about 50%. Although many disparate genomic
studies have been performed on this tumor type, a comprehensive understanding of the genomic alterations which drive
these tumors is still lacking. Additionally, no therapeutically targetable genomic subtypes are appreciated. We performed
an integrated genomic analysis with the goal of identifying genomic drivers and therapeutically targetable genomic
subtypes. 
Methods
Genomic DNA was isolated from 43 frozen tumor and adjacent normal specimens of oral cavity squamous cell carcinoma.
Exome capture sequencing was performed with Nimblegen capture reagents and sequencing was performed on SOLiD or
Illumina platforms. SNP analysis was performed on the Affymetrix SNP6.0 platform and analyzed with Partek, ASCAT,
GISTIC and R software. Total RNA was isolated with Tri-reagent and hybridized to Affymetrix Human Exon1.0ST arrays.
MicroRNA analysis was performed with Agilent rel12.0 miRNA arrays. DNA methylation was determined on the Illumina
Human Methy450 array. MRNA, microRNA, methylation and statistical analyses were performed with R.
Results
Multiplatform integrated genomic analysis was performed on 43 cases of OSCC in order to identify genomic drivers and
subtypes. The most frequently mutated, deleted, amplified and methylated genes were identified. These include; mutations
in NOTCH1, PIK3CA, HRAS, CASP8, MLL2 and FAT1, high level amplifications of CCND1, EGFR, MYC, and TP63,
and focal deletions of CDKN2A, CSMD1 and FAT1. Integrated analysis categorized the genomic alterations into driver
pathways.
Conclusion
The oral cancer genome contains frequent genomic alterations of many types. The majority of tumors contain at least one
oncogenic genomic alteration. However, the genomic landscape of OSCC is dominated by the loss of tumor suppressor
genes. Few novel targets were identified, indicating that therapeutic strategies must be developed for difficult to target
pathways.
Financial Disclosure (Curtis Pickering)
No
FDA Disclosure
Cleared:Yes
Keywords
HNSCC
genomics
integrated analysis
oncogenic drivers
Abstract ID: 118
Fenretinide/lymxsorb (4-HPR/LXS)tm Oral Powder Combined With Ketoconazole, A Fenretinide Metabolism
Inhibitor, Synergizes With Vincristine Antitumor Activity Against Recurrent Neuroblastoma Xenograft
Author List
1. Presenting Author: Lluis Lopez-Barcons
2. Additional Author: Hardeep Singh
3. Additional Author: Barry Maurer
4. Additional Author: Min Kang
5. Additional Author: C. Patrick Reynolds
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Survival from relapsed neuroblastoma (NB) is low and novel agents are needed to treat such children. Fenretinide (4-HPR)
is a synthetic retinoid with clinical activity against NB for which one mechanism of action is a tumor-selective increase in
dihydroceramides. 4-HPR/LXS is formulated as an oral powder lipid matrix LYM-X-SORBTM (LXS). We
have shown that ketoconazole (keto) increased 4-HPR plasma concentrations in mice by > 2-fold over 4-HPR alone.
Methods
We tested four human NB xenografts in nu/nu mice established from patients with progressive disease, CHLA-119 and
CHLA-90 (both TP53-mutant, multidrug-resistant lines), COG-N-415x and FU-NB-2006. 4-HPR/LXS was dosed at 240
mg/kg/day, keto at 38 mg/kg/day (both by oral gavagex5d/wk). Vincristine (VCR) was dosed at 0.5 mg/kg given 2d/wk
every other week by intravenous injection. Tumor and plasma concentrations of 4-HPR and metabolites (4-oxo-4-HPR and
4-MPR) were quantified by HPLC and sphingolipids by MS/MS.
Results
In CHLA-119 tumors, 4-HPR/LXS+keto increased 4-HPR( P<0.02) and 4-oxo-4-HPR (P<0.04) tumor concentrations by >
2-fold over 4-HPR/LXS alone. In mice with CHLA-119m xenografts, keto increased the complete response (CR) rate of
4-HPR/LXS from 1/10 mice to 5/10 mice. Survival for 350 days with 4-HPR/LXS was 10% compared to 50% of mice
treated with 4-HPR/LXS+keto (P<0.01). The CR rate in CHLA-119m for VCR + 4-HPR/LXS + keto was 5/10 mice
compared to 3/8 with 4-HPR/LXS+keto and 1/10 with VCR alone and mouse survival for 300 days with
4-HPR/LXS+keto+VCR was 50% vs 38% with 4-HPR/LXS+keto (P<0.01) and 10% for VCR alone (P<0.01). In
FU-NB-2006m xenografts, treatment with 4-HPR/LXS+keto+VCR increased the CR rate to 2/6 mice compared to 0/6 with
4-HPR/LXS+keto and mouse survival for 300 days with 4-HPR/LXS+keto+VCR was 2/6 (33%) vs 0% for VCR or
4-HPR/LXS Â± keto (P<0.01). In COG-415x mice, 1/9 treated with 4-HPR+keto+VCR had a CR (11%) vs 0% for the
other treatments (P<0.01). In CHLA-90m xenografts, no treatment achieved a response but survival was increased
(P<0.01) by 4-HPR/LXS+keto+VCR (110.6Â±41.4 days) over 4-HPR/LXS+keto (42.6Â±16.4 days) and controls
(22.2Â±6 days). Toxicity of the combination regimens by mouse body weight was negligible. 4-HPR/LXS alone or in
combination with keto and/or VCR increased tumor total dihydroceramide concentrations in xenograft tumors over those
measured in controls or tumors treated with VCR alone.
Conclusion
These data support the ongoing NANT phase I clinical trial of 4-HPR/LXS+keto and also support developing a future
clinical trial testing 4-HPR+keto+VCR in patients with recurrent NB. Supported by CPRIT RP100762.
Financial Disclosure (Lluis Lopez-Barcons)
No
FDA Disclosure
Cleared:Yes
Keywords
fenretinide
ketoconazole
vincristine
neuroblastoma
Abstract ID: 119
DUSP11 Is Required For Innate Immune Responses Mediated By Dendritic Cells
Author List
1. Presenting Author: Kalyan Nallaparaju
2. Additional Author: Yongliang Zhang
3. Additional Author: Joseph Reynolds
4. Additional Author: Roza Nurieva
5. Additional Author: Chen Dong
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
N/A
Introduction
Dual specificity phosphatases (DUSPs) have been shown to play a critical role in regulation of various cellular processes.
Aberrations in the expression patterns of DUSPs are associated with pathogenesis of a wide range of diseases. DUSP11, an
atypical member of DUSP family, was previously demonstrated to bind to ribonucleic acid-ribonucleoprotein (RNA-RNP)
complexes and RNA- splicing factors and is a p53 target gene. Recent in vitro studies by Caprara et al and
Hasler et al highlighted the importance of this molecule in cell proliferation, tumor suppression and chronic inflammation.
Our in vitro screening studies showed that DUSP11 expression is induced after activation of innate and
adaptive immune cells, suggesting that DUSP11 may play a role in regulation of immune responses. However,
DUSP11â€™s physiological function has not been elucidated in in vivo studies in an animal model. The
purpose of our study was to examine the role of DUSP11 in immune responses by employing DUSP11-knockout (KO)
mice that we generated in our laboratory.
Methods
Bone marrow derived dendritic cells (BMDCs) and CD4+ T-cells from spleen and lymph nodes were used to perform the
in vitro experiments. For the in vivo studies, DUSP11-KO mice and their wildtype counterparts
were either immunized with keyhole limpet hemocyanin (KLH) or infected with ovalbumin expressing Listeria
monocytogenes (LM-Ova) to study the role of DUSP11 in generating antigen specific responses.
Results
We found that compared with wildtype cells, DUSP11-KO antigen-presenting cells produced decreased levels of
proinflammatory cytokines during innate immune responses and that CD4+ T-cells showed increased proliferation after
activation but no apparent defect in in vitro T cell differentiation. However, our in vivo
experiments demonstrated that DUSP11-deficient mice were defective in antigen-specific T cell responses and that
they were more susceptible to LM-Ova infection when compared with wildtype mice. Using DC and T cell co-culture
experiments, we established that the DUSP11 signalling in DCs eventually regulated CD4+ T-cell activation.
Conclusion
Our results demonstrate the critical role of DUSP11 in innate immunity. Proinflammatory cytokines are essential
components of antitumor immune responses and the absence of DUSP11 results in the decrease in these cytokines
suggesting its essentiality in regulating antitumor immune responses. We will employ DUSP11-KO mice to test the role of
DUSP11 as a tumor suppressor in a colon cancer model and to investigate the immune mechanisms involved in the
process. Once DUSP11â€™s role is elucidated, modulating its expression may be a potential avenue for future anticancer
immunotherapy.
Financial Disclosure (Kalyan Nallaparaju)
No
FDA Disclosure
Cleared:Yes
Keywords
DUSP
Innate immune responses
Dendritic cells
Proinflammatory cytokines
Abstract ID: 121
Defining And Subverting Allele-specific Regulatory Networks In Cancer
Author List
1. Additional Author: Yunyun Ni
2. Additional Author: Amelia Hall
3. Additional Author: Anna Battenhouse
4. Additional Author: Matthew Cowperthwaite
5. Presenting Author: Vishwanath Iyer
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In cancer, somatic mutations drive tumorigenesis, progression and metastasis, and inherited germline polymorphisms affect
cancer susceptibility. While much attention is devoted to how these genetic variants affect protein coding genes, many
genetic variants in cancer occur in non-protein coding regions of the genome. A better understanding of the impact of
non-coding variants on gene regulation in cancer could expand the possibilities for targeted and personalized therapeutic
intervention, but integrating the role of non-coding variants has remained challenging. We envision that non-coding
variants affect gene regulatory networks in an allele-specific manner in tumor samples from different patients depending on
the patients' mutational complement and haplotypes. Identifying functional non-coding variants in cancer cells can thus
shed light on how mutations can alter gene regulatory networks in an allele-specific manner.
Methods
Our approach relies on identifying genetic variants that occur within transcription factor binding sites or sites of histone
modification, and are therefore likely to be functional. Data from deep sequencing of chromatin immunoprecipitated
samples (ChIP-seq) is analyzed using a SNP (single nucleotide polymorphism) discovery pipeline to identify genetic
variants in functional regulatory elements in the human genome. When these underlying variants are heterozygous, we can
simultaneously establish their impact on transcription factor binding or histone modifications. A parallel approach can be
applied to the interactions of miRNAs with their target mRNAs, which are also impacted by genetic variants. When applied
to data from cancer cells or tumors from patients, this approach can help reconstruct transcriptional and post-transcriptional
regulatory networks, and how they are altered in different tumors.
Results
We have carried out a proof-of-principle study using ChIP-seq data for transcription factors and histone marks, generated
from a number of normal human cells and cancer cells. The variants we identified from ChIP-seq data are highly
concordant with independently determined genotypes. We experimentally verified more than a hundred variants by
genomic sequencing, and estimated our false discovery rate at less than 5%. The variants we identified were significantly
enriched for disease-associated SNPs, and we identified allele-specific transcription factor binding in non-coding regions
that could distinguish between disease and normal haplotypes.
Conclusion
Our approach combines variant discovery and allele-specific analysis, but is selectively focused on functional regulatory
elements occupied by transcription factors or epigenetic marks, and will therefore be valuable for identifying the functional
regulatory consequences of non-coding variants in cancer.
Financial Disclosure (Vishwanath Iyer)
No
FDA Disclosure
Cleared:Yes
Keywords
Regulatory networks
non-coding variants
transcription factors
allele-specific
Abstract ID: 122
The Role Of Proliferation During Metastatic Invasion: From Modeling To Possible Treatments
Author List
1. Presenting Author: Eshel Ben-Jacob
2. Additional Author: Inbal Hecht
3. Additional Author: Ilan Tsarfaty
4. Additional Author: Jose Onuchic
5. Additional Author: Herbert Levine
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The ability of cancer cells to spread by invading adjacent tissue, often followed by distant metastasis, is a hallmark of
cancer. The varying histological patterns of tumors and experimental behavior of cancer cells suggest that tumor cells can
employ different cellular and molecular modes of invasion, depending on cell-type-specific, autonomous mechanisms, as
well as reactive mechanisms induced by the local microenvironment. The two main phenotypic mechanisms are: 1.
Amoeboid (or â€œpath finderâ€•) cells that are fast flexible and can squeeze through small gaps in the ECM (extracellular
matrix). 2. Mesenchymal (or â€œpath generatorâ€•) cells that are slower, more rigid and can decompose the ECM to pass
through. There are also multicellular invasion modes, which is not our focus here. Understanding the relative contributions
of these distinct mechanisms to the metastatic cascade according to tumor type, metabolic/physiological conditions and
morphogenesis stage is fundamental to the therapeutic targeting of cancer.
Methods
We present a conceptual and modeling framework for the analysis and assessment of the success rate, time-to-target, and
survival probability of amoeboid vs. mesenchymal modes. Similarly, we contrast invasion with and without proliferation,
according to the properties of the ECM, stress conditions, chemical cues such as HGF and signals secreted from the
primary tumor, and the role of mitosis and proteolysis. We treat the complex ECM geometry as a maze and employ
semi-realistic modeling of cell motility. Our approach includes metabolic and timing degrees of freedom. The theoretical
studies were compared with experimental efforts of cell navigation in specially designed microfluidic devices.
Results
The key results are: 1. in the absence of cell-cell competition (high resources) success rate depends mostly on proteolysis,
and mitosis slows down motility and invasion. 2. In the case of limited resources, elevated mitosis leads to longer time to
target with higher survival and higher success rate, whereas elevated proteolysis leads to shorter time to target with lower
success rate. Using experimental data regarding the effect of HGF (e.g. increase of metabolism, glycolysis and mitosis) the
model predicts elevated invasion success in the presence of HGF.Modeling can provide valuable tools for the interpretation
of experimental observations and for the design of new experiments. Model predictions can also provide clues about
therapeutic practice. Our results show that the success of cancer invasion can be lowered if drugs that increase proliferation
are given in conjunction with application of stress such as hypoglycemia or hypoxia.
Conclusion
Modeling can provide valuable tools for the interpretation of experimental observations and for the design of new
experiments. Model predictions can also provide clues about therapeutic practice. Our results show that the success of
cancer invasion can be lowered if drugs that increase proliferation are given in conjunction with application of stress such
as hypoglycemia or hypoxia.
Financial Disclosure (Eshel Ben-Jacob)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 123
Renal Clearable Luminescent Gold Nanoparticles For Tumor Imaging
Author List
1. Presenting Author: Jie Zheng
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Nanoparticles allow the combination of a variety of molecular imaging modalities and local treatment of lesions,
potentially catalyzing the shift of our current medical paradigm to â€œearlier detection and preventionâ€•. However, unlike
molecular probes used in clinical tumor imaging, most of nanoparticles are not renal clearable but rapidly sequestered by
reticuloendothelial system (RES) rich organs, resulting in high nanotoxicity and low tumor targeting efficiency and
specificity.
Methods
To address this challenge, in this talk, we will present a class of ~2nm luminescent gold nanoparticles (AuNPs),which
exhibit strong triplet-state emissions (J. Phys. Chem. C, 2010;7727). After coating the luminescent AuNPs with glutathione
ligand, we found that the glutathione coated luminescent AuNPs (GS-AuNPs) have little accumulation in the liver and
spleen, and can be cleared from the body through kidneys with an efficiency of 10~100 times better than the same sized
AuNPs (Angew. Chem. Int. Ed., 2011,3168). The origin of efficient renal clearance was attributed to the small particle size
and glutathione ligand, which minimizes serum adsorption during the blood circulation. Further studies on
pharmacokinetics of GS-AuNPs indicated that these renal clearable GS-AuNPs exhibit two-compartment pharmacokinetics
with a rapid t1/2Î± of 5.0 min, and a t1/2Î² of 12.7 hrs, very similar to those of the clinically available small molecule
contrast agents but different from those of most known nanoprobes (Angew. Chem. Int. Ed., 2012 in press).
Results
After introduced in the mice bearing breast tumors, these renal clearable GS-AuNPs can passively target the tumor with
high signal-to-background ratios. More importantly, the unbound AuNPs were also rapidly eliminated from normal tissues
to urine (Angew. Chem. Int. Ed, 2012, Submitted). The high contrast indexes of GS-AuNPs originate from short retention
time of the NPs in normal and long retention time in the tumor tissues.
Conclusion
Renal clearable luminescent GS-AuNPs behave like small molecules in passive tumor targeting. They can rapidly target
tumors due to their short distribution half life and are quickly eliminated from normal tissues. Long retention time of the
particles in tumor tissues, resulting from Enhanced Permeability and Retention (EPR) effect, makes them to target the
tumors at high efficiency and specificity. With these merits, renal clearable luminescent AuNPs are expected to further
advance potential applications of nanoparticles in clinical cancer imaging.
Financial Disclosure (Jie Zheng)
No
FDA Disclosure
Cleared:Yes
Keywords
Nanoparticles
Renal
Tumor
Imaging
Abstract ID: 124
Probing The Mechanical And The Metastatic Properties Of Tumor Cells Using A Microfluidic Cell Squeezer Device
Author List
1. Additional Author: Zeina Khan
2. Additional Author: Nabiollah Kamyabi
3. Additional Author: Souad Sennoune
4. Additional Author: Raul Martinez-Zaguilan
5. Presenting Author: Siva Vanapalli
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 02:55 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Studies have indicated that cancer cells have distinct mechanical properties compared to healthy cells. We are investigating
the potential of cell mechanics as a biophysical marker for diagnostics and prognosis of cancer. To establish the
significance of mechanical properties for cancer diagnostics, a high throughput method is desired. Although techniques
such as atomic force microscopy are very precise, they are limited in throughput for cellular mechanical property
measurements.
Methods
To develop a device for high throughput mechanical characterization of tumor cells, we fabricated a microfludic cell
squeezer device that contains narrow micrometer-scale pores. Fluid flow is used to drive cells into these pores mimicking
the flow-induced passage of circulating tumor cells through microvasculature. By integrating high speed imaging, the
device allows simultaneous characterization of five different parameters including blockage pressure, cell velocity, cell
size, elongation and entry time into squeezer.
Results
Using this device, we test both healthy and metastatic brain cells; prostate cancer cells of different metastatic potential and
leukemia cells. Scanning through the multidimensional parameters obtained from the device, we identify the key markers
that are indicative of metastatic potential. The throughput of the device is currently 100 cells/min. We will discuss how the
throughput of the device can be further increased to 1000 cells/min bringing it closer to the realm of clinical diagnosis.
Finally, the potential of the device for understanding the biomechanics of circulating tumor cells will be discussed.
Conclusion
The microfluidic cell squeezer device is capable of measuring the differences in metastatic potential of tumor cells.
Financial Disclosure (Siva Vanapalli)
No
FDA Disclosure
Cleared:Yes
Keywords
diagnostics
deformability
circulating tumor cells
microfluidics
Abstract ID: 125
West Texas Cancer Survivors Network (WTCSN)
Author List
1. Additional Author: Katherine Chauncey
2. Presenting Author: Barbara Pence
3. Additional Author: Janet Basom
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The West Texas Cancer Survivors Network was funded by CPRIT in 2010 â€“ 2012 to establish a cancer survivor network
and to provide cancer nutrition and quality of life information to cancer survivors in Health Services Region 1 of West
Texas. This project maintained the Cancer Nutrition Network for Texans which is a unique resource providing information
on nutrition and survivorship issues to Texans. The primary evaluation outcome was to assess the impact of participation in
the WTCSN on health-related quality of life (QoL) and health behaviors.
Methods
In the first year, infrastructure, community partnerships, and communication networks were established to support
recruitment to the network. Network enrollees received information on nutrition, physical activity, and quality of life. In
the second year, we conducted surveys by mail to assess the impact of the program on QoL and health habits in mostly
rural cancer survivors. All WTCSN participants were asked if they would be willing to participate in program evaluation
or research. If they answered yes, we asked them to complete an American Academy of Family Physician nutrition and
health habits survey and the RAND SF-36 questionnaire, a validated assessment survey for health-related QoL. IRB
approval was obtained from the TTUHSC IRB to do both the informed consent and the assessment by mail, as there was no
other way to reach the participants. Assessment was conducted at baseline, within a month of enrollment in the WTCSN
and then a second assessment after 6-8 months of participation in the WTCSN.
Results
As of August 8th, 471 persons representing 35 of the 41 counties in HSR1 enrolled in WTCSN. This includes 157 men and
314 women, ages 21-94. In December-January, 83 enrollees agreed to participate in the QoL survey which allowed for a
second assessment after 6-8 months. The impact of the WTCSN program was assessed with the SF-36 Health-Related
Quality of Life Survey. Preliminary data analysis showed that cancer survivors involved in the WTCSN program had
increases in many indicators of general health and well-being from pre- to post- intervention, from a 8.37 percentage point
increase for general health perception to a 26.41 increase in â€˜Noâ€™ answers to having a decrease in work or activity
due to health issues.
Conclusion
Participation in the West Texas Cancer Survivors Network improved the quality of life and the health behaviors of mostly
rural participants in HSR1.
Financial Disclosure (Barbara Pence)
No
FDA Disclosure
Cleared:Yes
Keywords
Survivors
Quality of life
Nutrition
Health behaviors
Abstract ID: 126
Rational Design Of Helix-Mimicking Small Molecules For Inhibiting BCL-2 Proteins In Prostate Cancer
Author List
1. Presenting Author: Jung-Mo Ahn
2. Additional Author: Rakesh Kumar
3. Additional Author: Kajal Bhimani
4. Additional Author: Jaspal Singh
5. Additional Author: Pradeep Patil
6. Additional Author: Joongsoo Kim
7. Additional Author: Yuefeng Du
8. Additional Author: Timothy Dobin
9. Additional Author: Jonathan Nguyen
10. Additional Author: Jer-Tsong Hsieh
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Apoptosis is an important cellular mechanism for tissue homeostasis and aberration in the process is well documented in
cancers including castration-resistant prostate cancer (CRPC). Since it is regulated by heterodimerization of BCL-2 family
proteins, disrupting such protein complexes is attractive for therapeutic intervention. Structural studies revealed that the
helical BH3 domain of pro-apoptotic proteins including BAK binds to a hydrophobic pocket in anti-apoptotic proteins like
BCL-xL. Whereas short peptides derived from BH3 domains may be used to inhibit the protein-protein interaction, they
have limitations that may severely compromise effective in vivo use, such as rapid enzymatic degradation, poor
bioavailability, and lack of membrane penetration. Thus, small molecules that mimic functions of helical BH3 peptides
would be of great interest in developing potential therapeutic candidates.
Methods
Recently, we have developed a tris-benzamide scaffold to mimic protein helical structures. The rigid tris-benzamide
scaffold can place three functional groups corresponding to the side chains found at the i, i+4, and i+7 positions in a helix.
To represent the hydrophobic surfaces of BH3 domains, we have designed a number of tris-benzamides based on the
sequences of the BH3 domains of various pro-apoptotic BCL-2 proteins. These rationally designed BH3 mimetics were
then examined for their binding affinity to anti-apoptotic BCL-2 proteins, inhibition of cell proliferation of various prostate
cancer cell lines, mechanism of action, and in vivo efficacy.
Results
Using the synthetic methods that we have established, a number of tris-benzamides mimicking BH3 domains were
efficiently prepared. Testing on their binding affinity to anti-apoptotic BCL-2 proteins, we have identified several leading
compounds that also showed high metabolic stability and cell permeation. These compounds were found to be effective in
inhibiting cell growth of several prostate cancer cell lines, such as DU-145 and PC-3, and provided evidences of apoptosis
examined by cytometry-based assays. In addition, they showed an ability to suppress tumor growth on pre-clinical animal
model.
Conclusion
In this study, we have demonstrated that small molecules can be rationally designed from the structures and sequences of
BCL-2 proteins and that these BH3 mimetics show a high potential in inhibiting prostate cancer cell lines by disrupting the
target protein complexes.
Financial Disclosure (Jung-Mo Ahn)
No
FDA Disclosure
Cleared:Yes
Keywords
Helix-mimicking small molecules
Apoptosis
Prostate Cancer
Bcl-2 proteins
Abstract ID: 127
Impact Of Kidney Progenitor Cell Differentiation Status In Wilms Tumorigenesis
Author List
1. Presenting Author: Le Huang
2. Additional Author: Sharada Mokkapati
3. Additional Author: Qianghua Hu
4. Additional Author: Weihua Tian
5. Additional Author: Vicki Huff
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Wilms Tumor (WT) is a pediatric cancer of the kidney. The typically triphasic histology of tumors is suggestive of a tumor
stem cell that can variably differentiate, producing the bulk of the tumor. The observation of distinctive subsets of tumors
further suggests that each arises from cells at different stages of differentiation. However, it is unknown what types of cells
in the mesenchyme and at what stage of differentiation are susceptible to transformation into WT. Therefore, we
hypothesize that WT can arise from fetal kidney cells at different differentiation stages and that specific kidney progenitor
populations at risk produce different types of WTs with respect to tumor initiation, growth and pathology.
Methods
We used kidney progenitor-specific CreER transgenes to mosaically ablate Wt1 (Wilms Tumor Gene 1) in the
context of Igf2 biallelic expression and test to see if these different types of progenitor give rise to mouse WT or not. If
tumors occur, we are further interested in what the differences in tumor biology are between tumors arising from different
progenitors. Moreover, we ablated Wt1 in a high proportion of progenitor cells to study the effects of Wt1 ablation on
kidney development and how Wt1 ablation predisposes progenitor cell to malignant transformation.
Results
We have generated cohorts of mutant mice and littermate controls and are assessing them for tumor development.
Additionally, as for the developmental study, we found that Wt1 ablation in stromal progenitors has no obvious effect on
nephrogenesis. However, when Wt1 is ablated in nephrogenic progenitors, nephrogenesis is blocked. The mutant kidneys
at E19.5 contain fewer mature nephron structures and an increased number of stromal cells. Furthermore, the nephrogenic
zone (NZ), where the progenitor cells reside, is expanded. Cells in the expanded NZ express the progenitor markers and are
proliferative. This suggests that Wt1 ablation in the nephron progenitors prevents the cells from epithelial differentiation
and the cells maintain their proliferation and self-renewal property in the NZ.
Conclusion
These results will help us understand the functions of Wt1 in the progenitors and provide significant insights into the cell
origin of WT and the mechanisms of WT initiation and progression. Potentially it will help us to develop personalized
therapies that target the tumors specifically and trigger the most effective responses according to the tumor cell origin.
Financial Disclosure (Le Huang)
No
FDA Disclosure
Cleared:Yes
Keywords
Wilms Tumor
Mouse kidney development
Wt1
Kidney progenitor
Abstract ID: 128
Conditional Activation Of Notch Signaling In Osteoblast Initiates Osteosarcoma In Mice
Author List
1. Presenting Author: Jianning Tao
2. Additional Author: Shan Chen
3. Additional Author: Ming Ming Jiang
4. Additional Author: Brian Dawson
5. Additional Author: Terry Bertin
6. Additional Author: Yangjin Bae
7. Additional Author: Francis Gannon
9. Additional Author: Lawrence Donehower
10. Additional Author: Brendan Lee
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 03:10 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Human osteosarcoma (OS) is the most common primary bone cancer, comprising approximately 20% of all bone tumors
and about 5% of pediatric tumors overall. Most OS occurs sporadically and our understanding of its molecular basis is still
limited. Recently, we found that human and mouse p53 mutant osteosarcoma tumor samples show evidence of upregulated
Notch signaling. Moreover, chemical or genetic inhibition of Notch signaling decreased tumor growth in a xenograft
mouse model of human osteosarcoma. Notch signaling plays an important role in the developmental processes and tissue
homeostasis. Altered Notch signaling has been associated with several cancers in which Notch can act both as an oncogene
and tumor suppressor depending on its spatiotemporal expression. 
Methods
To generate a mouse osteosarcoma model and examine the role of Notch signaling in bone tumorigenesis, we utilized
conditional and transgenic mouse models that constitutively express single copy of Notch NICD in the committed
osteoblast.
Results
The resulting compound Notch gain-of-function (GOF) mutant mice developed osteosclerosis at early age.
Histomorphometric and molecular analysis of cavarial and long bones indicated that Notch could stimulate proliferation of
immature osteoblasts while inhibiting their differentiation into mature osteoblasts. This gain of function phenotype was
reminiscent of osteoblastic tumors. Subsequent studies of the GOF mice showed that they spontaneously developed bone
tumors including osteosarcoma with complete penetrance and had a survival mean time of nine months. These tumors
display many of the characteristic features of human osteosarcomas, including radiographic, histological, and being highly
metastatic. To explore a genetic interaction of Notch and p53 pathways in the development of OS, the GOF mice were bred
with p53-conditional mice. We found that p53-null GOF mice showed significantly shortened latency prior to
tumorigenesis, as mice developed OS at a mean time of five months.
Conclusion
OS development in the GOF mice reveals a dominant function of Notch signaling in the development of osteosarcoma. Our
data also support that p53-Notch interaction may be a critical mechanism in OS development. Owing to the similarity
between murine osteosarcoma and human osteosarcoma, our model may be valuable for understanding the molecular
genetics of osteosarcoma and for conducting preclinical trials.
Financial Disclosure (Jianning Tao)
No
FDA Disclosure
Cleared:Yes
Keywords
Osteoblast
Notch
Osteosarcoma
Tumor
Abstract ID: 129
UCHL5 In Association With The Ino80 Chromatin Remodeling Complex Promotes Metastasis In Melanoma
Author List
1. Presenting Author: Diane Scaduto
2. Additional Author: Kunal Rai
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Metastatic melanoma is one of the most fatal cancers in the western world affecting more than 76,000 Americans and
taking the lives of almost 10,000. Patients with metastatic melanoma that has spread to one or more organs have a median
survival of only seven months. Novel treatment strategies are desperately needed for this dismal cancer. To design new
targeted therapies however, we need to gain better understanding of genes promoting the metastatic process.
Methods
Using a combination of comparative oncogenomic and functional genomics approaches, we have identified 18
pro-metastatic genes including UCHL5, a deubiquitinase that is also part of the chromatin remodeling complex, Ino80.
Results
Here, we demonstrate that UCHL5 over-expression in various melanoma cell lines in vitro and when xenografted in
immunocompromised mice leads to an increased invasive property and metastasis to the lungs. From in vitro studies, we
found that UCHL5 also promotes tumorigenic properties of non-transformed melanocytes. Consistently, knockdown of
UCHL5 leads to reduced tumor volume and incidence of human melanoma cell lines in nude mice. In mechanistic studies,,
we show that the association of UCHL5 with the Ino80 chromatin remodeling complex is critical for pro-invasive function.
Additionally, UCHL5 can promote TGFÎ² signaling which may be important and play a role in its pro-invasiveness.
Conclusion
Collectively, our data illustrates a model where UCHL5 may promote TGFÎ² signaling through the Ino80 chromatin
remodeling complex leading to melanoma metastasis. These results suggest that UCHL5 is a promising target for the
treatment of metastatic melanoma.
Financial Disclosure (Diane Scaduto)
No
FDA Disclosure
Cleared:Yes
Keywords
Melanoma
Metastasis
UCHL5
None
Abstract ID: 130
ACP5 Promotes Tumorigenesis And Metastasis In Melanoma Through Its Phosphatase Activity
Author List
1. Presenting Author: Dong Yang
2. Additional Author: Chengyin Min
3. Additional Author: Timothy Heffernan
4. Additional Author: Chang-Jiun Wu
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Tartrate resistant acid phosphatase 5 (ACP5) is a metalloenzyme that has been studied as a marker of bone metastases in
cancer patients. For example, clinical studies have shown that high level of ACP5 is predictive for shorter survival in
prostate cancer with bone metastasis. Similarly, increased expression of ACP5 has been found in malignant breast, ovarian
and melanoma tissue. Recently, in an effort to integrate genetically engineered mouse models and functional genomic
screens, ACP5 was identified as a prognostic biomarker in early-stage melanoma, promoting both tumorigenesis and
metastasis. However, the mechanism responsible for its pro-tumorigenic and pro-metastatic function remains largely
unknown.
Methods
We examined the pro-tumorigenic and pro-metastatic function of ACP5 and its phosphatase-deficient mutant in xenograft
model. We also knocked down one of ACP5â€™s substrates, SPP1, and analyzed the effect in invasion assay.
Results
The abolishment of its phosphatase activity blocks the elevated tumorigenesis and metastasis conferred by overexpression
of ACP5. Knockdown of SPP1 inhibits tumor cell invasion promoted by ACP5 in vitro.
Conclusion
Here we demonstrate that the phosphatase activity of ACP5 is required for its role in melanoma. We also show SPP1
mediates its function in vitro. Collectively, our studies identify ACP5 not only as a novel mediator of
metastasis in melanoma, but also as a novel target for the treatment of this deadly disease.
Financial Disclosure (Dong Yang)
No
FDA Disclosure
Cleared:Yes
Keywords
melanoma
ACP5
SPP1
None
Abstract ID: 131
Selective Aldose Reductase Inhibitors To Treat Colon Cancer
Author List
1. Presenting Author: Suzanne Tomlinson
2. Additional Author: Drew Bryant
3. Additional Author: Lydia Kavraki
4. Additional Author: Stanley Watowich
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Aldose reductase (ALR2) has recently been shown to be an important mediator of colon cancer signaling pathways. The
reduction of glutathione (GS-) conjugated aldehydes by ALR2 produces intermediates that are involved in inflammation
and cancer-signaling pathways. Although ALR2 inhibitors have been shown to arrest tumor growth in mice (Srivastava
2010), the majority of these inhibitors failed clinical trials due to undesirable side effects. It is believed that the observed
side effects were largely due to cellular toxicity resulting from non-selective inhibition of ALR2 and accumulation of toxic
aliphatic aldehydes. Analysis of our crystal structure of ALR2 with a bound GS-aldehyde analog revealed a GS-binding
site separate from the catalytic site, implying selective inhibitors of the GS-binding site could be developed that would
prevent GS-aldehyde reduction and subsequent cancer signaling, while still allowing the reduction of toxic aliphatic
aldehydes.
Methods
FASST cluster analysis was performed on the ~100 ALR2 structures in the Protein Data Bank (PDB) to group ALR2
structures based on the conformation of the GS-binding site. Docking studies used the Directory of Useful Decoys (DUD)
database of known ALR2 binders and the AUTODOCK Vina program. Molecular dynamic calculations were performed
with CHARMM; trajectory conformations were clustered with FASTT to identify dominant conformations of the ALR2
GS-binding site. Vina was used to dock the DUD ALR2 database and a library of ~625,000 drug-like compounds to
representative ALR2 structures from each cluster of the MD trajectory.
Results
Docking the DUD ALR2 database to representative structures from each PDB and MD cluster resulted in a near ideal
discrimination between known ALR2 binders and non-binders. Docking the drug-like library to representative structures
from the most populated conformational clusters produced a composite ranking of ligand binding energies; predicted
tight-binding inhibitors were ordered from commercial chemical companies and tested in biochemical kinetic assays to
identify novel ALR2 inhibitors selective for the GS-binding site.
Conclusion
Docking to multiple target conformations produces near-ideal discrimination of binders and should increase the probablity
of identifying novel inhibitors by virtual docking.
Financial Disclosure (Suzanne Tomlinson)
No
FDA Disclosure
Cleared:Yes
Keywords
aldose reductase
colon cancer
inhibitor
drug
Abstract ID: 132
Developing Inhibitors Of K-Ras Plasma Membrane Targeting
Author List
1. Additional Author: Dharini van der Hoeven
2. Additional Author: Kwang-jin Cho
3. Presenting Author: John Hancock
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 03:45 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Ras proteins regulate signaling pathways important for cell growth, differentiation and survival. Oncogenic mutant Ras
proteins are commonly expressed in human tumors, with mutations of the K-Ras isoform being most prevalent. For
biological activity K-Ras must undergo posttranslational processing and associate with the plasma membrane. Inhibition of
plasma membrane localization is a valid therapeutic approach to block signal transmission by oncogenic K-Ras, however
the K-Ras trafficking pathway from the ER to the plasma membrane has not been characterized. We therefore devised a
high content screening assay to search for inhibitors of K-Ras plasma membrane association. We report here our results
from screening the Prestwick library, containing ~1800 FDA-approved drugs.
Methods
We established MDCK cell lines stably expressing mGFP targeted to the plasma membrane by the full C-terminal
hypervariable region of K-Ras (GFP-CTK) or H-Ras (GFP-CTH), and MDCK cell lines stably expressing full-length
oncogenic mutant GFP-K-RasG12V or GFP-H-RasG12V. MDCK cells were chosen because the columnar morphology
and basolateral distribution of Ras facilitates automated confocal imaging. For primary screening we used the cell lines
expressing GFP-CTK and GFP-CTH. The GFP-CTK and GFP-CTH fusion proteins undergo the same posttranslational
processing and membrane trafficking as the cognate full length Ras protein, but are biologically inert and better preserve
the morphology of the parental MDCK line.
Results
As proof of concept we used the assay to screen the Prestwick library. We identified fendiline, an L-type calcium channel
blocker, as a specific inhibitor of K-Ras plasma membrane targeting that had no detectable effect on the localization of Hand N-Ras. Other classes of L-type calcium channel blockers did not mislocalize K-Ras suggesting a mechanism of action
that is unrelated to calcium channel blockade. Fendiline treatment did not inhibit K-Ras posttranslational processing but
significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to ER, Golgi,
endosomes and cytosol. Fendiline significantly inhibited signaling downstream of constitutively active K-Ras, and
endogenous K-Ras signaling in cells transformed by oncogenic H-Ras. Consistent with these effects, fendiline blocked the
proliferation of endometrial cancer cell lines transformed by oncogenic mutant K-Ras. We are currently screening other
chemical and natural products libraries and have assembled a suite of additional compounds that mislocalize K-Ras.
Conclusion
Our results suggest that inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras-specific
anticancer therapeutics. Further characterization of the K-Ras trafficking pathway is warranted and may reveal novel and
specific molecular targets for therapeutic intervention.
Financial Disclosure (John Hancock)
No
FDA Disclosure
Cleared:Yes
Keywords
K-Ras
Plasma membrane
Inhibitors
High content screening
Abstract ID: 133
Nanochannel Implantable Drug Delivery System For Breast Cancer Preventive Therapy With Aromatase Inhibitors
Author List
1. Presenting Author: Silvia Ferrati
2. Additional Author: Shyam Bansal
3. Additional Author: Erika Zabre
4. Additional Author: Eugenia Nicolov
5. Additional Author: Thomas Geninatti
6. Additional Author: Juliana Sih
7. Additional Author: Melissa Landis
8. Additional Author: Mauro Ferrari
9. Additional Author: Alessandro Grattoni
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In the more than 60% of breast cancer cases where development and growth depend on estrogen, aromatase inhibitors, in
particular letrozole, are promising chemopreventive agents that inhibit estrogen biosynthesis. Side effects associated with
the conventional oral administration are a limiting factor for long term use. Implantable silicon nanochannel delivery
systems (nDS), which are now industrially microfabricated and ready for clinical translation, could deliver low-dose,
sustained and local delivery of this drug. In this study we evaluated the in vitro and in vivo release profiles of letrozole
from nDS devices to establish a method to assess drug concentrations in vivo and to characterize the drug release kinetic.
Methods
In vitro release kinetics and stability of letrozole from two different nDS configurations were evaluated by means of high
performance liquid chromatography (HPLC) for the selection of the optimal nDS for the following in vivo studies. The in
vivo pharmacokinetics and toxicity of nDS-released letrozole was performed in female Sprague-Dawley rats, implanting
the device in the subscapular region, and compared to conventional oral administration. Letrozole plasma concentrations
were quantified for 70 days by means of liquid chromatography/ mass spectroscopy (LC/MS). A complete blood toxicity
panel was also performed.
Results
Constant and sustained release of letrozole was achieved in vitro from two nDS over a period of 90 days with a release rate
of 2 and 10 Âµg per day. These results correlate with the in vivo data showing constant plasma concentrations of letrozole
released from nDS (2ng/mL, around 2 Âµg released per day) over a period of 70 days, as compared to the characteristic
peak profile of oral administration (60ng/mL, peak level). No toxicity was found associated with the employment of nDS.
Conclusion
The success of chemoprevention for breast cancer relies on improving patientsâ€™ compliance while enhancing efficacy
and circumventing side effects of treatment. The results here reported demonstrate the feasibility of our approach for breast
cancer prevention; data on estrogen levels and bone are in progress.
Acknowledgements: This work was supported by a UTHealth Innovation for Cancer Prevention Research Post-doctoral
Fellowship, CPRIT grant #RP101503 and Emily Hermann Cancer Research Laboratory Fundation.
Financial Disclosure (Silvia Ferrati)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer Prevention
nanotechnology
implantable devices
None
Abstract ID: 136
Elucidation Of Epigenetic Signature Of Cancer Cells
Author List
1. Presenting Author: Jia Zeng
2. Additional Author: QInghua Wang
3. Additional Author: Brian Kirk
4. Additional Author: Jianpeng Ma
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
CPRITfigure_08092011.jpg
Summary
Introduction
Aberrant epigenetic alterations mediated by Polycomb/Trithorax group (PcG/TrxG) proteins and DNA methylation
(DNAM) are key contributing factors of carcinogenesis. A very troubling property of cancer cells is their ability to
self-perpetuate, which parallels that of stem cells. Recent studies reveal that PcG and TrxG are responsible for maintaining
stem cell renewal and pluripotency and they may even directly influence DNA methylation. In this study, we aim at further
elucidating the involvement of PcG/TrxG/DNAM in cancer development and identifying the epigenetic signature of cancer
cells that is distinct from that of healthy stem cells.
Methods
Synergizing results from multiple representative studies, we compiled a comprehensive epigenetic profile database which
includes the genes targeted by PcG, TrxG or DNAM in cancer cells and embryonic stem (ES) cells respectively. A
systematic bioinformatics analysis was then performed on these genes in a pair-wise manner at the cellular level. We
identified genes that have a unique epigenetic profile in cancer/ES cells and investigated the correlations between these
three epigenetic modifiers in cancer/ES cells. We also developed a simple in-silico algorithm to predict the genes that are
upregulated/downregulated in cancer cells.
Results
These original analyses provide strong evidence that PcG, TrxG and DNAM are extensively involved in carcinogenesis
and the epigenetic profile of cancer cells is distinct from that of ES cells. After analyzing some representative genesâ€™
differential epigenetic regulation pattern in three cell lines (ES, PC3 and EP156T), we derived a gene signature of prostate
cancer stem cells. A prostate cancer specific validation procedure reveals that our results correlate well with several recent
studies on cancer stem cells. Our analysis suggests that the regulation pattern of PcG/TrxG/DNAM has a distinctive
signature in cancer cells and the enriched functions of the target genes specific to cancer cells are strikingly different from
those specific to ES cells. The genes that have a unique epigenetic profile in cancer or ES cells are mostly involved in
immune response, cell-cell signalling and homeostasis. Our study also reveals that the correlation between the epigenetic
regulators of interest presents a unique pattern in cancer cells.
Conclusion
Collectively, the cancer specific characteristics identified by our study can provide useful knowledge to the development of
effective epigenetic therapies that directly target the self-renewal pathways of cancer cells without posing threat to healthy
stem cells.
Financial Disclosure (Jia Zeng)
No
FDA Disclosure
Cleared:Yes
Keywords
cancer epigenetics
polycomb/trithorax group proteins
DNA methylation
cancer stem cell
Abstract ID: 137
Texas Disability Technology Initiative: Independent Living And Employment For Cancer Survivors And People
With Disabilities
Author List
1. Presenting Author: Perla Villarreal
2. Additional Author: Maxwell Raithel
3. Additional Author: Edward Elms
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In 2011, cancer and its management including surgery, radiation and chemotherapy caused 8.4% of long-term disability
claims and is the second leading cause (14.6%) of new disability claims ("CDA Annual Long-Term Disability Claims
Review," 2011). Cancer survivors with disabilities have difficulty with activities of daily living (ADL), independent living
and employment. Many people with disabilities who have difficulty with independent living and work will have better
outcomes thanks to assistive technology (AT). Unfortunately AT has not been used effectively to assist cancer survivors
and other people with disabilities in overcoming the barriers they face to independent living and employment (Frieden et
al., 2012). An initiative has been undertaken in the state of Texas to develop and promote the use of AT for the benefit of
people with disabilities. The purpose of this study was to determine the extent to which people with different types of
disabilities use and need AT.
Methods
In July and August 2012 a nationwide survey was implemented to determine the extent to which people with disabilities
use assistive technologies. After a 6-week period, 492 people responded to the survey which was available online. Survey
respondents were recruited through online letters and notices posted by organizations of people with disabilities. Current
usability and dependency, barriers to obtaining AT as well as satisfaction with current AT was assessed. Data from the
survey was compared with data obtained from a similar study of people with disabilities in Texas in 2011.
Results
65% of survey respondents indicated they used AT everyday in the workplace. Over half of the respondents (57%) reported
a need for additional AT, the cost of which they reported as the biggest barrier to obtaining AT with 269 assertions (55% of
responses). The respondents demonstrated satisfaction with the current AT in the market - 279 (57%) responses expressed
to be either very satisfied or somewhat satisfied. However 47% of the respondents expressed a need for AT that has yet to
be invented or developed. There were 297 respondents in 2011. Selected survey results were comparable indicating that the
information obtained through the surveys was generalized and valid.
Conclusion
People with disabilities including cancer survivors depend on AT for their everyday lives particularly when in the
workplace. Further development of affordable AT has the potential to decrease the proportion of people with disabilities
who are unemployed and improve independent living outcomes for those who wish to be full participants in community
life.
Financial Disclosure (Perla Villarreal)
No
FDA Disclosure
Cleared:Yes
Keywords
Independent Living
Cancer Survivor
Assistive Technology
None
Abstract ID: 138
Shared Governance: Improving Oncology Nursing Knowledge And Care Across A Healthcare Network
Author List
1. Presenting Author: Sylvia Danko
2. Additional Author: Lisa Brannan
3. Additional Author: Sandra Miller
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Shared Governance empowers nurses to develop quality nursing practices. This is a description of how shared governance
is increasing oncology nursing knowledge and skill, and promoting evidence based oncology care in the Seton Healthcare
Family. Seton expanded rapidly in the past three years, resulting in the addition of units where oncology care is provided
with varying levels of frequency and nurse experience. Concerns surfaced for ensuring safe, standardized, evidenced based
oncology nursing care network wide. We have a long tradition of shared governance. Creating an Oncology Subspecialty
Council as a forum for bringing forward practice concerns evolved naturally. Council goals are to increase oncology nurse
knowledge and competency, improve network oncology patient care processes, and support less experienced nurses at
lower volume sites.
Methods
Members are nurse representatives from each unit and clinic providing oncology care, and related disciplines such as
pharmacy, clinical nutrition, and infection prevention. Variations in practice are discussed, literature review and research
conducted, and a consensus is reached on what best practice standards are. Nurses are educated and informed the standards.
Initiatives to date include neutropenia management and blood stream infection prevention, early recognition and
management of oncologic emergencies, and chemotherapy/biotherapy administration. 
To improve chemotherapy/biotherapy administration, we reviewed and categorized the past yearâ€™s incident reports
involving agent administration (N= 49). We found that 63% of the errors resulted from unclear communication between
pharmacy and nursing. Nurses at the newer, lower volume sites also reported low confidence with chemotherapy
administration, and requested a tool to facilitate the process. We worked with pharmacy to revise our
Chemotherapy/biotherapy Policy and develop a chemotherapy/biotherapy communication checklist, implemented in
November 2011.
Results
Chemotherapy/biotherapy incident reports resulting from interdisciplinary communication problems from January through
June have dropped by 30%. Nurses report increased confidence in chemotherapy administration with the use of the
checklist. An evaluation of nurse perception of administration skill and knowledge is being conducted via survey with
Likert scale; results will be available by September.
Conclusion
Shared governance has proven an effective vehicle for improving oncology nurse knowledge, confidence, and skill and for
promoting evidence based care in the expansive Seton Healthcare Family.
Financial Disclosure (Sylvia Danko)
No
FDA Disclosure
Cleared:Yes
Keywords
health professional education/training
oncology nursing
chemotherapy/biotherapy administration
None
Abstract ID: 139
Near-infrared Fluorescence Imaging Of Impaired Lymphatics In A Head And Neck Cancer Survivor
Author List
1. Presenting Author: I-Chih Tan
5. Additional Author: Latisha Smith
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Fig1.jpg
Summary
Introduction
Lymphedema (LE) that arises after irradiation and/or surgical dissection of lymph nodes is a common complication in
cancer survivors after cancer treatment. This debilitating post-cancer disease has been a major impact on the survivorship
and a major financial burden for cancer care. Of more than 53000 new head and neck (HN) cancer cases this year in US, it
is expected that as many as 75% will encounter HN LE following cancer treatment. Management of HN LE is challenging
because of complicated geometry and complex lymphatic structure in HN regions, as well as limited options for treatment.
Mapping of lymphatic architecture and function would allow more effective treatment of HN LE, which will lead to better
cancer survivorship. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR)
fluorescence lymphatic imaging together with 3-dimensional photogrammetry (3DP) to understand the lymphatics, and to
help better manage cancer-related LE in a HN cancer survivor.
Methods
A subject, who developed severe HN LE after treatments of HN squamous cell carcinoma, was recruited for this imaging
study. Immediately after 9 intradermal injections of 25 Âµg indocyanine green each in the face and neck region, skin
surface was illuminated with a diffused excitation light of 785 nm, and NIR fluorescence images at 830 nm wavelength
were collected using a custom-built imaging system. Manual lymphatic drainage (MLD) therapy was performed through
the guidance of the images. Also, 3DP of the face was used to monitor response to therapy.
Results
NIR fluorescence images revealed some abnormal lymphatic structures in the HN region, and helped identify some
functioning vessels and draining lymph nodes. More effective LE therapy was achieved through the guidance lymphatic
mapping. Precise geometry of facial structure was obtained using 3DP, and detection of small changes in edema between
therapy sessions was achieved. This analysis allowed longitudinal assessment of LE to evaluate the effect of therapy.
Conclusion
In this study, we were able to map HN lymphatics in a HN cancer survivor, who suffered from LE, direct more effective
MLD using NIR fluorescence imaging, and assess therapy efficacy using 3DP. The results provided some preliminary data
that allowed us to design a new study to longitudinally assess the lymphatics in cancer treatment and recovery using NIR
fluorescence imaging pre- and post- cancer treatments. The new study will be supported by CPRIT Bridging the Gap award
(RP120941).
Financial Disclosure (I-Chih Tan)
No
FDA Disclosure
Cleared:Yes
Keywords
fluorescence imaging
lymphatics
None
None
Abstract ID: 140
A Texaphyrin-Oxaliplatin Conjugate That Overcomes Both Pharmacologic And Molecular Mechanisms Of
Cisplatin Resistance In Cancer Cells
Author List
1. Presenting Author: Jonathan Arambula
3. Additional Author: Zahid Siddik
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The FDA approved platinum agent cisplatin demonstrates significant activity in several cancer types, but is plagued by
intrinsic and acquired resistance that translates into low 5-year survival rates. This resistance observed is multifactorial and
includes pharmacologic as well as molecular mechanisms of resistance such as failure to initiate p53 mediated apoptotic
pathways. 
Texaphyrins are members of the â€œexpanded porphyrinâ€• class of macrocycles and have been explored as experimental
therapeutic agents. Motexafin gadolinium (MGd), a specific gadolinium(III) texaphyrin complex has been found to
selectively localize to tumors. 
Based on the limitations of platinum based anticancer agents and the utility of texaphyrins to localize in tumors, we
hypothesized that texaphyrin-platinum conjugates could increase platninum concentrations within tumor cells. 
Methods
A combination of inorganic and organic synthetic chemistry was employed to synthesize conjugates. Biological studies
include cell proliferation assays, determination of intracellular platinum, quantification of DNA-platinum adducts, FACS
analysis, Western Blots.
Results
Results indicated that our conjugate (oxaliTEX) was highly potent than as judged from cell proliferation assays providing
similar IC50 values in A2780 and 2780CP ovarian cancer cells. Further, and most significantly, no evidence of resistance
was observed, This lack of resistance stands in marked contrast to the 2-fold resistance seen with oxaliplatin (a complex
that lacks the localization features that we think are inherent to oxaliTEX).
Intracellular Pt levels from oxaliTEX were significantly higher than most other complexes. In fact, compared to
oxaliplatin, oxaliTEX is capable of delivering over twice the platinum payload to A2780 cells in addition to a 4-fold
advantage in resistant 2780CP, thus displaying no cross resistance.
Cell cycle disruption was studied by FACS analysis. The induction of apoptosis was confirmed to be similar to that of
oxaliplatin. The activation of p53, phosphorylated p53, and p21 was confirmed by Western Blot analysis.
Conclusion
The ability to enhance the uptake of a Pt payload into resistant 2780CP ovarian cancer cells distinguishes oxaliTEX from
other Pt delivery strategies, and identifies this conjugate as the first small molecule platinum complex capable of
overcoming both pharmacologic and molecular mechanisms of resistance in vitro. It is normally presumed that success of
chemotherapy in resistant disease may require addressing each of the many mechanisms of resistance. However, it is
evident from the present study that targeting only a few critical cellular impediments with a designer drug may be
sufficient to achieve a markedly improved therapeutic response.
Financial Disclosure (Jonathan Arambula)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 141
Exploiting The TGFÎ²:Betaglcyan Complex For The Design Of Novel Ligand-Trap TGFÎ² Inhibitors For The
Treatment Of Advanced Breast And Prostate Cancer
Author List
1. Presenting Author: Maria Villarreal
2. Additional Author: Andrew Hinck
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Transforming growth factor Î² (TGF-Î²) isoforms are 25kDa homodimeric proteins that negatively regulate cell growth,
modulate immune cell function and stimulate differentiation. They play a complex role in cancer, where they function as
tumor suppressors in normal and early neoplastic cells, but as promoters of tumor growth and metastasis in advanced
breast, brain, and prostate cancer. TGF-Î²s signal by cooperatively assembling heteromeric receptor complexes. They first
bind the type II receptor (TÎ²RII), which allows the low affinity type I receptor (TÎ²RI) to bind. While TGF-Î²1 and
TGF-Î²3 bind TÎ²RII with high affinity, TGF-Î²2 binds TÎ²RII weakly. It requires the co-receptor betaglycan to bind TÎ²RII
and signal. In contrast to the membrane bound form, soluble betaglycan, which is naturally produced under certain
circumstances, especially by cancer cells, binds TGF-Î²s with near nanomolar affinity and suppress tumor growth,
metastasis, and invasion. In this research, we have investigated the molecular basis by which betaglycan binds TGF-Î²s and
promotes receptor binding with the goal to use this information to generate highly potent receptor-based ligand traps for
cancer treatment.
Methods
To accomplish this, we studied the binding of the TGF-Î² isoforms to the betaglycan extracellular domain as well as it two
independent binding domains, BGe and BGu, using Surface Plasmon Resonance (SPR), Small Angle X-ray Scattering
(SAXS) and single molecule TIRF-based fluorescence imaging.
Results
The results suggest that betaglycan binds such that the endoglin-like domain is positioned near the center of the TGF-Î²
homodimer adjacent to TÎ²RII, while the uromodulin-like domain is positioned off center and blocks the second TÎ²RII site.
This allows betaglycan to potentiate the binding of TÎ²RII by binding and concentrating TGF-Î²2 on the cell surface, while
at the same time leaving one of the TÎ²RII binding sites available for binding. This allowed us to design two ligand traps,
one, designated REU, in which the C-terminus of the extracellular domain of TÎ²RII was fused to the N-terminus of the
extracellular domain of betaglycan, and a second, designated RER, in which two TÎ²RIIs were fused on either end of BGe.
Both these ligand traps bind all three TGF-Î²s with considerably greater affinity compared to 1D11, a pan-TGF-Î²
monoclonal antibody that exhibited limited efficacy in clinical trials for malignant melanoma and renal cell carcinoma.
Conclusion
REU and RER, because of their smaller size and greater affinity for the TGF-Î² isoforms compared to 1D11, therefore
represent potential new agents for treating cancers stimulated by TGF-Î² with improved efficacy.
Financial Disclosure (Maria Villarreal)
No
FDA Disclosure
Cleared:Yes
Keywords
TGF-Beta inhibitor
Ligand Trap
Receptor Complex
Structure
Abstract ID: 142
Physiologic Capacity As A Predictor Of Postoperative Outcomes
Author List
1. Presenting Author: Vicky Woodruff
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
abs_fig.jpg
Summary
N/A
Introduction
An estimated 12 million individuals undergoing non-cardiac surgery in the United States each year will experience
postoperative complications. The costs of complications are manifested in the growing healthcare economic burden and
patientsâ€™ reduced quality of life, future economic productivity, and shortened long-term survival. This research is
grounded in a conceptual framework derived from pilot study results and literature in physiologic capacity and stress. The
study tested the hypothesis that physiologic capacity is a predictor of postoperative complications and associated costs in
three types of oncological surgery (esophagectomy, hepatectomy, and radical cystectomy).
Methods
Gas exchange data was gathered during maximal Cardiopulmonary Exercise Test (CPET).
Results
Data analysis strategies included forward step-wise binary logistic regression. Results showed the physiologic capacity
parameter of peak oxygen uptake (PV02) of >20 mL/min/kg, plus a heart rate time (HRTIME) of <5 minutes (for the heart
rate to fall at or below 100 bmp after stop test) as the multivariate predictive model (67% sensitivity and 92% specificity)
for complications in the hepatectomy group. Conversely, an anaerobic threshold (AT) of >10 mL/min/kg was found to be
the univariate predictive model (33% sensitivity and 91% specificity) for the radical cystectomy group. No predictor was
found for the esophagectomy group. Each predictive model also predicted between 89% - 100% of actual length of stay
and hospital costs. Lastly, dependant variable analysis showed trends in common complications regardless of surgical type
and complications associated with individual surgical types. Furthermore, trends indicated the type and timing of when
complications were most likely to occur. Esophagectomy showed 60 events over 60 days with the greatest cluster between
postop days 1 â€“ 25. Radical cystectomy showed 21 events over 12 days with the greatest cluster occurring on postop day
4 and then 11&12. Hepatectomy showed 36 events over 7 days, with the clustering occurring during postop days 7 - 12.
Overall, if hepatectomy and radical cystectomy patients made it past day 12, they appeared to be â€œout of the woodsâ€•.
Conclusion
Conclusions imply that a paradigm shift from subjective to objective phenotypic physiologic risk assessment may be
possible with secondary windows of complication mitigation opportunities identified. This paradigm shift in risk
assessment approach may affect standards of care, policies, procedures, and decision-making changes in the healthcare
industries and surgeon practice, resulting in better patient outcomes, fewer surgical complications, and increased quality of
life.
Financial Disclosure (Vicky Woodruff)
No
FDA Disclosure
Cleared:Yes
Keywords
Physiologic Capacity
Postoperative
Complications
Predicting
Abstract ID: 144
Establishing A Prioritization Pipeline To Accelerate Validation Of Driver Events Discovered In PDACS
Author List
1. Presenting Author: Turgut Dogruluk
2. Additional Author: Yiu-Huen Tsang
3. Additional Author: Ping Wu
5. Additional Author: Nikitha Nair
6. Additional Author: Kenneth Scott
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease that remains one of the most challenging
malignancies to treat successfully. Developing improved therapies requires a better understanding of the molecular
pathways driving PDAC progression, and identifying underlying casual genomic events will inform new targets for
therapeutic intervention and biomarkers for early detection. Recognizing this, the International Cancer Genome
Consortium (ICGC) is generating a compendium of pancreatic cancer-associated genomic alterations. Effective translation
of this knowledge into clinical endpoints will require new systems capable of distinguishing "driver" events from
biologically-neutral "passengers" in the appropriate biological context. The work described here aims to functionalize the
pancreatic cancer genome using a genetic aberration â€œprioritization pipelineâ€• geared toward functionally validating
thousands of putative driver events to discover the most promising candidates for entry into biomarker and drug
development platforms.
Methods
First, we developed a new high-throughput technology permitting high efficiency, site-directed mutagenesis and cloning of
target genes in a single reaction tube. When combined with our human gene platform consisting of over 32,000
sequence-verified open reading frames (ORFs), we are employing this mutagenesis strategy to engineer aberrations
discovered from PDAC sequencing studies. Second, we devised an innovative molecular barcoding technique that allows
high-throughput â€œtaggingâ€• of these mutant ORFs with small DNA barcode sequences that enable pooled ORF screens
and downstream barcode enrichment quantification using next generation sequencing. Third, we developed a novel human
pancreatic duct epithelial (HPDE) cell line designed to express activated KRAS upon doxycycline induction.
Results
We have validated our high-throughput mutagenesis technology across hundreds of mutations. We have achieved a 100%
success rate across all mutations attempted in ORFs ranging from 567 to 3309 base pairs with GC content ranging 42-79%.
We have also fully optimized our molecular barcoding and detection strategies through proof-of-concept studies designed
to detect positive tumor enrichment of bona fide driver oncogenes originating from barcoded ORF pools consisting of
driver and non-driver genes. Finally, we have confirmed that our newly developed inducible KRAS cell line forms ductal
tumors upon KRAS activation, and inactivation through doxycycline withdrawal leads to complete and sustained tumor
regression in line with KRASâ€™s role in tumor maintenance.
Conclusion
Together, these technologies are enabling discovery of KRAS cooperating aberrations using a first-in-kind in vivo positive
selection screen for mutant drivers of PDAC tumorigenesis and metastasis. Our studies have high potential to inform new
drug targets/biomarkers critically needed for PDAC patients who currently have no other effective treatment options.
Financial Disclosure (Turgut Dogruluk)
No
FDA Disclosure
Cleared:Yes
Keywords
High-throughput mutagenesis and barcoding
in vivo positive selection screens
Pancreatic ductal adenocarcinoma (PDAC)
Cancer driver discovery
Abstract ID: 145
Evaluation Of The Improvement Of Mucoadhesion By Chitosan-Glutathione Liposomes Orally Administered In
Rats With HNSCC By Noninvasive Imaging
Author List
1. Presenting Author: Yi-Hsiu Chung
2. Additional Author: Beth A. Goins
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
cprit.jpg
Summary
Introduction
The goal of this study was to investigate a novel liposome formulation as an oral cancer drug delivery system in a head and
neck squamous cell carcinoma (HNSCC) rat xenograft model. The liposomes contain a novel asparagine-derived
lipid(Asp-liposomes) to impart acid resistance during transit through the gastrointestinal(GI) tract and a coating of
chitosan-glutathione to enhance intestinal mucoadhesion and permeation. To monitor GI transit and bioavailability after
oral administration, the liposomes encapsulated doxorubicin as a model drug and are radiolabeled with technetium-99m
(Tc-99m) to permit non-invasive nuclear imaging.
Methods
Tc-99m were loaded into Asp-liposomes encapsulating doxorubicin by ammonium sulfate gradient.
Tc-99m-Dox-Asp-liposomes were coated with chitosan-glutathione (CS) by magnetic stirring for 1 hour at 25ÂºC. Coating
efficiency of CS-Asp-liposomes was determined after separation of free CS by centrifugation at 15000g for 30min.
Uncoated Tc-99m-Dox-Asp-liposomes served as control. Coated or uncoated liposomes were given to the nude rats with
HNSCC xenograft (n=5 per group) orally by gavage, followed by planar imaging and blood collection at varying time
points. At 4 hr after oral administration, one animal in each group was sacrificed and the intestines were fixed for
doxorubicin fluorescent microscopy. The others were sacrificed immediately after 8hr imaging session to determine the
Tc-99m tissue biodistribution in the animal. Doxorubicin was extracted from plasma, liver and spleen and the fluorescence
measured. Regions-of-interest (ROIs) of stomach and intestines were drawn on the planar images. The statistical
differences between the two groups were tested by Studentâ€™s t-test.
Results
Coating efficiency of chitosan-glutathione on the surface of Asp-liposomes was about 86%. The diameter of Coated-Asp
liposomes was increased to 1200nm from 140 nm for uncoated Asp-liposomes. Analysis of 2 hr images indicated the
CS-Asp-liposomes moved from stomach to intestine whereas more uncoated Asp-liposomes remained in stomach.
Additionally, CS-Asp-liposomes showed less radioactivity in ROIs of intestinal images at 4 hr which corresponded to more
radioactivity in blood, liver, spleen and kidneys through absorption by the intestinal enterocytes. The bioavailability of
extracted doxorubicin from liver(p<0.01)) and spleen(p<0.01)) were 34.37+/-10.21 % and 14.37+/-2.37% for
CS-Asp-liposomes and 14.07+/-0.99 % and 7.76+/-1.18% for uncoated Asp-liposomes. Fluorescent microscopy of
intestinal sections also showed the accumulation of higher amounts of CS-Asp-liposomes in the serosal side, in contrast to
the more uniform distribution for uncoated Asp-liposomes.
Conclusion
Chitosan-glutathione-liposomes are a potential oral drug delivery system that can increase the bioavailability of oral cancer
drugs.
Financial Disclosure (Yi-Hsiu Chung)
No
FDA Disclosure
Cleared:Yes
Keywords
Oral administration
Chitosan-liposomes
HNSCC rat xenograft model
Tc-99m and doxorubicin encapsulation
Abstract ID: 146
RNA Nanoparticles For Biomedical Applications
Author List
1. Presenting Author: Alexey Koyfman
2. Additional Author: Kirill Afonin
3. Additional Author: Bruce Shapiro
4. Additional Author: Boxue Ma
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Specific small interfering RNAs (siRNAs) designed to silence specific oncogenic pathways can be used for cancer therapy.
However, non-modified siRNAs cannot be used practically to silence genes since they are unstable in the blood stream,
thus having a short half-life, and encounter difficulties in crossing membranes due to their negative charges.
Three-dimensional nanoscale RNA scaffolds have the potential for broad use in nanotechnological and biomedical
applications.
Methods
The design strategies of RNA scaffolds employ assembly principles borrowed from natural RNA structures. We
functionalized RNA nanoscaffolds with six therapeutic siRNAs, visualized the structures with electron cryo microscopy,
and tested these therapeutic constructs in several cell lines.
Results
Our Cryo-EM reconstruction was in agreement with the nanoscaffold design. We showed a significant increase in gene
silencing with RNA nanoscaffolds compared to the silencing caused by equal amounts of individual siRNAs.
Conclusion
These results show a higher potency of RNA-based therapeutic nanoparticles and the potential for RNA nanoscaffolds for
siRNA silencing.
Financial Disclosure (Alexey Koyfman)
No
FDA Disclosure
Cleared:Yes
Keywords
RNA nanoscaffolds
siRNA silencing
RNA nanoparticles
None
Abstract ID: 147
Missed Opportunities: Racial And Socioeconomic Disparities In Emergency Presentation Of Colorectal Cancer
Author List
1. Presenting Author: Sandi Pruitt
2. Additional Author: Nicholas Davidson
3. Additional Author: Samir Gupta
4. Additional Author: Yan Yan
5. Additional Author: Mario Schootman
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 02:55 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Emergency presentation for colorectal cancer (CRC) is common and associated with high morbidity and mortality. African
Americans and those with lower socioeconomic status (SES) experience higher CRC morbidity and mortality, and higher
rates of emergency CRC presentation may, in part, account for these disparities. We hypothesized that African Americans
and individuals with low SES have higher rates of emergency CRC presentation.
Methods
We examined disparities in emergency CRC presentation using nationally representative 1992-2005 SEER-Medicare data
of U.S. adults aged â‰¥66 years with invasive CRC. Emergency CRC presentation (the primary outcome) was defined as
a newly diagnosed CRC associated with: obstruction, perforation, or an inpatient admission requiring immediate medical
intervention (e.g. for severe, life threatening conditions) identified using Medicare claims with ICD-9 and admission type
codes. We used logistic regression to compare associations of race and SES status with emergency CRC presentation,
adjusting for sociodemographic (age, sex, Medicaid status, year of diagnosis, urban/rural residence at diagnosis), tumor
(SEER historic stage, left/right side tumor location, grade, histology), and clinical (history of the following in the prior
year: preventable hospitalizations, comorbidity, endoscopic testing) covariates.
Results
We identified 88,859 patients with CRC during the study period, 29.0% of whom presented emergently (of these, 81.3%
had an emergency admission, 31.6% obstruction, and 4.2% perforation). In unadjusted analyses, CRC patients more likely
to present emergently included African Americans (vs. whites OR: 1.64 95% CI: 1.57-1.72) and those living in census
tracts with the highest poverty rate (â‰¥20% vs. <10% poverty OR: 1.31 95% CI: 1.26-1.37). In a single multivariable
model, after adjusting for all covariates including tumor stage, African Americans (vs. whites AOR: 1.29 95% CI:
1.21-1.37) and those living in census tracts with the highest poverty rate (â‰¥20% vs. <10% poverty AOR: 1.10 95% CI:
1.04-1.16) continued to be more likely to present emergently.
Conclusion
In this population-based study, racial and socioeconomic disparities are evident in emergency presentation of CRC, which
may account for some of the observed disparities in morbidity and mortality. Targeted efforts to increase CRC screening in
these populations would reduce this preventable disparity.
Financial Disclosure (Sandi Pruitt)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 148
Magnetic Resonance Imaging Of Tumor Extracellular pH Using A Paramagnetic CEST Contrast Agent
Author List
1. Presenting Author: Todd Soesbe
2. Additional Author: Yunkou Wu
3. Additional Author: Khaled Nasr
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
148_abstract_image.jpg
Summary
N/A
Introduction
Paramagnetic chemical exchange saturation transfer (PARACEST) agents use slow-to-intermediate proton and water
molecule exchange between exogenous chelates and the bulk water to create contrast in magnetic resonance imaging
(MRI). It was recently shown that the frequency-shifted bound water molecule exchange peak of a Eu3+DOTA-based
PARACEST agent (Î”Ï‰ = 50 ppm) could be used to accurately measure physiological pH levels in vitro. Using this
Eu3+-based agent to create a tumor pH map in vivo is problematic though, mainly because the same saturation pulse used
to activate the exogenous PARACEST agent also activates the magnetization transfer (MT) effect between endogenous
tissue macromolecules and the bulk water. The tissue MT effect, which spans from 100 ppm to -100 ppm, can greatly
reduce the sensitivity of the PARACEST agent in vivo. We hypothesized that the tissue MT effect could be avoided
entirely and the PARACEST agent sensitivity greatly increased by using a Tb3+DOTA-based chelate that has a water
molecule exchange peak (Î”Ï‰ = -600 ppm) far outside the MT window. This MRI method could be used to create
non-invasive, high-resolution tissue pH maps for the early detection and diagnosis of cancer and the evaluation of cancer
therapy.
Methods
Two versions of the Tb3+DOTA-based PARACEST agent were synthesized, each having a slightly different water
molecule exchange rate at 37 Â°C. The sensitivity of each bound water peak frequency to pH (i.e., Î”ppm/pH) was
measured in vitro by creating an array of pH values (6.0 to 8.0 pH) and taking the CEST-spectrum (i.e., the bulk water
signal intensity vs. saturation frequency) of each sample at 9.4 T. These data were then used to create a pH calibration
curve for pH mapping in vivo. Initial in vivo data used renal uptake due to glomerular filtration to create pH maps of
healthy mouse kidneys and bladder.
Results
As expected, the increase in the bound water chemical shift when moving from Eu3+ to Tb3+ (50 ppm to -600 ppm,
respectively) led to a corresponding increase in Î”ppm/pH for the bound water peak. This increase in Î”ppm/pH leads to
both an increase in pH sensitivity and a decrease in error due to Bo inhomogeneity caused by susceptibility changes within
the subject. The in vivo pH maps of the mouse kidneys and bladder are in agreement with physiological values.
Conclusion
By using a lanthanide ion that possesses a large bound water chemical shift (Î”Ï‰) a highly-sensitive pH PARACEST
contrast agent was created that is not impaired by the MT effect. 
 
Financial Disclosure (Todd Soesbe)
No
FDA Disclosure
Cleared:Yes
Keywords
MRI
PARACEST contrast agent
extracellular pH
molecular imaging
Abstract ID: 149
Nanohydrogels As Delivery Systems Of Antineoplastic Drugs And siRNA To Overcome Multidrug Drug Resistance
In Cancer Treatment
Author List
1. Presenting Author: Mar Creixell
2. Additional Author: Diane Forbes
3. Additional Author: Hannah Frizzell
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on
the cell membrane and by increasing anti-apoptotic pathways. By encapsulating drugs into nanoparticles that bypass the
efflux pumps drug efflux is reduced. The use of nanocarriers to deliver siRNA prevents both renal clearance and RNase
degradation by protecting siRNA chains, thus increasing their half-life in blood. Delivering drugs and siRNA against
anti-apoptotic pathways implicated in cancer resistance could be more effective in overcoming resistance of cancer cells
than treatment of cancer cells with either siRNA or drugs.
Methods
Polycationic nanoparticles were synthesized with a hydrophobic core, for encapsulation of a chemotherapeutic agent, and a
positive surface charge, to complex siRNA. The monomers 2-dietylaminoethyl methacrylate (DEAEME), tert-butyl
methacrylate (t-BMA), and the polymer poly(ethylene glycol) methyl ether methacrylate (PEG-MA) were polymerized
under a UV source, after emulsion in water. Tetraethylene-glycol dimethacrylate (TEGDMA) was used a cross linker. We
developed and assessed a method to load a chemotherapeutic drug into the nanoparticle core that allows monitoring of drug
concentration at any time point. The same method was used to perform release studies siRNA was complexed into the
nanoparticle surface by electrostatic interactions.
Results
The resulting nanoparticles were pH responsive and had a size and surface charge that ranges from 140nm and +14.4mV,
at pH 4, to 90nm and +6.57mV, at pH 8. The loading rate for a model drug was about 57%, after 24 hours of incubation in
water at room temperature. The ratio drug/particle after 24h of incubation in water at room temperature was 0.0017 (w/w).
The release of the drug was studied at pH 4.3 and at pH 7.4. Knocking down efficiency of the siRNA complexed
nanoparticles was studied in Panc-1 cells.
Conclusion
Biocompatible polycationic pH responsive nanoparticles were synthesized for delivery of siRNA and an antineoplastic
drug. Due to their membrane disruption properties at endosomal pH nanoparticles are capable of loading and releasing a
model drug in a timely manner, disrupting the endosome delivering the payload to the cytosol, and knocking down targeted
genes. This is a promising delivery system for siRNA and drug delivery to overcome multidrug resistance in cancer
treatment.
Financial Disclosure (Mar Creixell)
No
FDA Disclosure
Cleared:Yes
Keywords
Nanohydrogels
Multidrug resistance
siRNA
Drug Delivery
Abstract ID: 150
In-depth profiling of activated transcription factors with a concatenated tandem array of transcription factor
response elements.
Author List
1. Presenting Author: Sung Yun Jung
2. Additional Author: Chen Ding
3. Additional Author: Jun Qin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Transcription factors (TF) are families of proteins that bind to specific DNA sequences, or transcription factor response
elements (TFREs), and function as regulators of many cellular processes. Due to their low abundance, direct quantitative
measurement of TFs on a proteome scale remains a challenge. In this study, we report the development of an affinity
reagent that permits identification of endogenous TFs at the proteome scale.
Methods
The affinity reagent is composed of a synthetic DNA containing a concatenated tandem array of the consensus TFREs
(catTFRE) for the majority of transcription factor families. We referred to transcription factor binding database JASPAR to
select known concensus TFREs for different TF families. To design the catTFRE construct, we used 100 selected TFREs
and placed two tandem copies of each sequence with a spacer of three nucleotides in between, resulting in a total DNA
length of 2.8 Kb. We synthesized and cloned the catTFRE sequence into a pUC57 vector and prepared the catTFRE
affinity reagent by PCR amplification with biotinylated primers. We then incubated nuclear extracts with the biotinylated
catTFRE. The resulting protein-DNA complexes were digested with trypsin and either directly analyzed with mass
spectrometry, or undergone an additional separation step with IEF prior to MS analysis. Both isotope-based (SILAC or
QconCAT) and label free quantification can be used in this workflow.
Results
Using this catTFRE to enrich TFs from cells, we were able to identify as many as 400 TFs from a single cell line and a
total of 779 TFs from 9 human cancer cell types, covering more than 50% of the gene products that code for the
DNA-binding transcription factors in the genome. Employing a label-free mass spectrometry based quantification strategy,
we were able to measure proteome-wide changes in levels of activated transcription factors in response to exogenous
stimulation.
Conclusion
In summary, the catTFRE strategy presented here enables high-throughput identification and quantification of DNA
binding activity for all cellular transcription factors. We envision that this technology will serve as a potent tool for
elucidation of the molecular effects of drug actions, evaluation of drug efficacy, and concurrent discovery of secondary
drug effects.
Financial Disclosure (Sung Yun Jung)
No
FDA Disclosure
Cleared:Yes
Keywords
Proteomics
Mass spectrometry
Transcription factor
None
Abstract ID: 151
Cancer Screening Education For Nurses In Rural Or Medically Underserved Areas Of Texas
Author List
1. Presenting Author: Joyce Dains
2. Additional Author: Carol Vreeland Dallred
3. Additional Author: Gwen Corrigan
4. Additional Author: Molly Frankel
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The goal of the program was to decrease the cancer burden in rural or medically underserved areas in Texas by improving
cancer screening knowledge, skill, and practices of nurses. The unequal burden of cancer on ethnic minorities and on the
medically underserved is well documented. Texans living in rural or low-income areas are more likely to lack cancer
screening services and have higher cancer rates. Nurses in their own communities from ethnic and racial sub-populations
are ideally positioned to educate and encourage screening activities, to participate in the provision of services, and to
appreciate and address the cultural norms of the community. Nurses cite lack of knowledge as a primary barrier to cancer
prevention education and screening.
Methods
Advanced Practice Nurses traveled to seven Texas communities and taught nurses to incorporate cancer prevention
education and screening into clinical practice. Each program included classroom instruction and a clinical component for a
subset of participants to learn clinical breast examination (CBE). Instructional methods included lecture, group discussion,
hands-on clinical training and case studies. The Kirkpatrick Four-Level Evaluation Model for training programs was used
to evaluate program outcomes: reaction; learning (knowledge); behavior (skill); and results (practice). Post program focus
group sessions were held in two of the communities to discuss impressions of the program.
Results
Reaction: Program satisfaction was > 4 out of 5 on a Likert Scale. Learning: Knowledge in cancer
screening improved significantly (p<0.001) as measured by pre and posttests. Behavior: Participants who
underwent CBE instruction successfully completed a skills checklist. Confidence in performing CBE increased
significantly (p<0.001) following CBE instruction as measured by the Grundy confidence scale. Results:
Participants were followed for 12 months after their program to quantify their cancer screening education and services.
Approximately 200 participants provided cancer prevention education and services to more than 12,880 Texans in rural
and/or medically underserved areas of Texas. The focus group participants expressed positive comments regarding the
program and identified barriers to change in clinical practice.
Conclusion
This program provided an important service to nurses and patients in rural and medically underserved Texas. Participants
used their improved knowledge and skill to impact the health of almost 13,000 Texans. The program was successful
because it was conducted with front-line providers, in their own communities, using proven strategies, with intensive
follow-up. The program demonstrated its value as a cost effective means of partnering with communities to assure the
delivery of cancer screening education and services.
Financial Disclosure (Joyce Dains)
No
FDA Disclosure
Cleared:Yes
Keywords
screening
education
rural
underserved
Abstract ID: 152
Tumor Suppressive Function Of MicroRNA34c In Osteosarcoma
Author List
1. Presenting Author: Yangjin Bae
2. Additional Author: Jianning Tao
4. Additional Author: Jason Yustein
6. Additional Author: Brendan Lee
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
MicroRNAs (miRNAs) have been implicated in diverse biological roles including development, cell proliferation,
apoptosis, metabolic stress and tumorogenesis. During tumor development, many miRNAs function as both tumor
suppressors and oncogenes. The miR-34 family which functions as tumor suppressive miRNA, is evolutionally conserved
and directly regulated by p53 in response to DNA damage and oncogenic stress, inducing apoptosis and cell-cycle arrest.
Interestingly, our recent study of osteoblast- specific gain of function miR-34c mice (Col1a1 2.3 kb-miR34c) has
demonstrated a critical role for miR-34c during bone development and homeostasis by targeting multiple components of
the Notch signaling pathway. We and others have shown that an osteoblast-specific Notch gain of function mouse model
can stimulate proliferation of immature osteoblasts while inhibiting their differentiation into mature osteoblasts. This gain
of function phenotype leads to the development of osteoblastic tumors and indeed, Notch signaling was also up-regulated
in human osteosarcoma (OS) samples. Consistent with this observation, our transcriptional profiling of OS from p53 +/mice exhibited elevated expression of Notch signaling, which leads to the proliferative and metastatic potential of OS. It
has been also shown that genetic and epigenetic alterations in OS lead to decreased miR-34 expression levels. Here, we
hypothesize that the miR-34 family plays a critical role in the negative regulation of Notch signaling in osteoblasts and
exhibits a potential mechanism to modulate the proliferative effect of Notch in the committed osteoblast progenitors.
Hence, perturbation of the crosstalk between miR-34s, p53, and Notch may contribute to the pathogenesis of OS.
Methods
To examine whether GOF miR-34c can affect OS formation and progression, Col1a1 2.3kb-miR34c was crossed with
Col1a1 2.3kb Cre/+; p53 f/f (osteoblast-specific loss of p53 allele). Clinical endpoints include survival, hind limb paralysis,
tumor progression and metastases. We have performed xenografts using the hOS cell line 143b (p53-/-) stably expressing
miR-34c (143b-34c) together with proper controls, and examined whether GOF of miR-34c affected OS progression in
vivo.
Results
In our genetic mouse model of Col1a1 2.3kb-miR34c; Col1a1 2.3kb Cre/+; p53 f/f, we have found that GOF miR-34c mice
trend towards increased survival compared to Col1a1 2.3kb Cre/+; p53 f/f mice. Furthermore, xenograft studies using hOS
cell line 143b-34c shows regression of tumor growth compared to 143b-controls.
Conclusion
Overall these results suggest that miR-34c plays a critical role as tumor suppressor during OS formation. The underlying
moelcular mechanim of tumor suppressive function of miR-34c is currently being pursued.
Financial Disclosure (Yangjin Bae)
No
FDA Disclosure
Cleared:Yes
Keywords
Osteosarcoma
miR-34c
Notch signaling
P53
Abstract ID: 153
Targeting No Production In Melanoma And CLL via Irreversible Inhibitors
Author List
1. Presenting Author: Gayle Burstein
2. Additional Author: Yun Wang
3. Additional Author: Shougang Hu
4. Additional Author: Joyce Er
5. Additional Author: Suhendan Ekmekciouglu
6. Additional Author: Arturo Cardounel
7. Additional Author: Varsha Gandhi
8. Additional Author: Walter Fast
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Nitric oxide (NO) biosynthesis is important in normal cell function and tumor progression. In order to target NO in cancer
cells, tissue specific inhibitors are necessary. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) catalyzes the
hydrolysis of asymmetric NÏ‰, NÏ‰-dimethyl-L-arginine (ADMA), an endogenous inhibitor of
nitric oxide synthase (NOS). Targeting DDAH1 is a way to inhibit NO production in a tissue specific manner without
affecting all three isoforms of NOS. We have developed covalent DDAH1 inhibitors in order to address aberrant NO
production in certain cancer cells.
Methods
A series of irreversible DDAH1 inhibitors have been synthesized and studied in vitro as well as in melanoma and B cell
chronic lymphocytic leukemia (CLL) cell lines. We previously discovered a small warhead, 2-chloroacetamidine, which
covalently modifies the active site of DDAH1. To create more potent and specific irreversible inhibitors, we linked this
warhead with L-ornithine and with L-lysine to yield, respectively, Cl-NIO and Cl-NIL. We determined the inhibition
constants of the compounds for purified DDAH1 and their effect on melanoma and CLL cell lines.
Results
The starting inhibitor, 2-chloroacetamidine, has a kinact value of 3.9 Â± 0.1
min-1 and a KI of 300 Â±2 0 Î¼M. We reasoned that linking this fragment to an
amino acid component might increase potency. Cl-NIO has a kinact value of 0.34 Â± 0.07
min-1 and a KI of 1.3 Â± 0.6Î¼M. Cl-NIL has a kinact value of 0.30 Â± 0.09
min-1 and a KI of 0.12 Â±0.06 Î¼M. To gauge the selectivity of Cl-NIO for
DDAH1, we tested for off-target inhibition of human arginase and NO synthase. Only weak reversible inhibition of
arginase (KI 3.1mM) and no inhibition of eNOS (at 500Î¼M) were observed. A significant
reduction in nitrite and nitrate was observed when Cl-NIO was applied to A375 melanoma cells, indicating decreased NO
production. Both Cl-NIO and Cl-NIL induced apoptosis in leukemic lymphocytes isolated from patients with CLL.

Conclusion
Linking 2-chloroacetamidine with L-ornithine was expected to have a greater than additive effect on binding potency
(KI). However, the effect was weaker than expected, perhaps due to an unoptimized linker.
Cl-NIL increased the linker length, and led to a 10-fold improvement in KI.This fragment-based
approach to irreversible inhibitor design is a promising strategy and has resulted in the most potent DDAH1 inhibitor to
date.
Financial Disclosure (Gayle Burstein)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 154
Low-Dose Perifosine As A Novel Anti-Telomerase Therapy
Author List
1. Presenting Author: Brody Holohan
2. Additional Author: Hirotoshi Hoshiyama
3. Additional Author: Neal Jones
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Introduction: Tumor cells are dependent on telomerase in order to maintain their telomeres and their
replicative potential. As part of our CPRIT-funded research, we performed a screen to identify genes that, when inhibited,
interfered with any step of telomerase action on the telomere and caused progressive telomere shortening. While
characterizing the resulting hits, it became clear that a large number of them were downstream of the AKT pathway.
Perifosine is an AKT inhibitor in Phase III clinical trials for AKT-dependent tumors. We hypothesized that Perifosine, at
doses sufficiently low that it would not inhibit the growth of even non-AKT dependent tumor cells, might nonetheless
modify enough of these targets to cause telomere shortening in a telomerase-dependent manner. The toxicity of such low
doses might be sufficiently low on normal cells to allow it to be used as a long-term telomerase inhibitor.
Methods
Methods: A variety of cell lines were cultured in the presence of Perifosine, either as a single agent or in
conjunction with Imetelstat, a competitive inhibitor of telomerase enzymatic activity. Telomeres were measured over time
by Terminal Restriction Fragment (TRF) assays, while telomerase activity was measured by the Telomeric Repeat
Amplification Protocol (TRAP) assay.
Results
Results: Perifosine caused dose-dependent telomere shortening in cancer cells, but not in
telomerase-negative fibroblasts. Doses of Perifosine 20 times lower than those used in acute therapy on AKT-dependent
tumors were sufficient to cause telomere shortening without significantly affecting cellular growth rates. Perifosine in
conjunction with Imetelstat produced an additive telomere shortening rate, though Perifosine had no effect on TRAP
activity at doses that caused telomere shortening, suggesting that it is interfering with telomerase action through a variety
of post-translational mechanisms.
Conclusion
Conclusion: Perifosine may be a novel avenue to bring anti-telomerase therapy to the clinic in a rapid
fashion, and to improve existing anti-telomerase therapies. Because of the low doses required to interfere with telomerase,
it should have a high therapeutic ratio with minimal effects on normal cells.
Financial Disclosure (Brody Holohan)
No
FDA Disclosure
Cleared:Yes
Keywords
Telomerase
AKT
Perifosine
Telomerase Inhibitor
Abstract ID: 156
Promoting Colorectal Cancer Screening In An Online Weight Loss Community Through Narratives And Peer
Support: A Pilot Feasibility Study
Author List
1. Presenting Author: Kevin Hwang
2. Additional Author: Allison Ottenbacher
3. Additional Author: Amanda Graham
4. Additional Author: Eric Thomas
5. Additional Author: Rick Street, Jr
6. Additional Author: Sally Vernon
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Online health communities offer an opportunity to use narratives and peer support to promote colorectal cancer (CRC)
screening in larger groups than are typically seen in other settings. Because obesity is associated with excess CRC
incidence and mortality as well as lower CRC screening rates, delivering narratives and peer support in an online weight
loss community could be an efficient approach to reaching high-risk individuals. The purpose of this pilot study was to
evaluate the feasibility and potential impact of narratives and peer support for promoting CRC screening in an online
weight loss community.
Methods
Members of an online weight loss community who were not up-to-date with CRC screening were randomized to BASIC or
ENHANCED interventions (n=153 each). Both groups received online education about CRC screening. The ENHANCED
group was invited to join an online team to read narratives about CRC screening written by other members of the online
community (narrators) and to interact with the narrators and other study participants through online forums. Change in
CRC screening attitudes was assessed at 1 month and CRC screening was assessed by self-report at 6 months.
Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted, with and without adjustment for relevant baseline
variables.
Results
Participants were mostly female (92%) with mean age 56 years and BMI 32. Over 90% in both groups viewed the
educational information. Only 57% (87/153) in the ENHANCED group joined the online team; 34% (52/153) posted at
least 1 message on the forums. In ITT and PP analyses, the ENHANCED group had a greater improvement in stage of
change than the BASIC group. In the PP analysis, the ENHANCED group had a greater increase in response efficacy of
CRC screening (+0.14 [0.37] vs +0.01 [0.46], p=0.03) compared to BASIC group. In the ITT analysis, there was no
significant difference in CRC screening at 6 months (ENHANCED 19% vs BASIC 16%, AOR 1.3, 95% CI 0.72-2.39). In
the PP analysis, fecal occult blood testing was higher in the ENHANCED group vs BASIC group (14% vs 7%, adjusted
OR 2.5, 95% CI 1.01-6.17).
Conclusion
In an online weight loss community, the ENHANCED intervention featuring narratives and peer support for CRC
screening was feasible, but user engagement was suboptimal. While the ENHANCED intervention improved short-term
cognitive outcomes and rate of fecal occult blood testing, modifications to improve user engagement are likely needed to
affect overall CRC screening rates.
Financial Disclosure (Kevin Hwang)
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal cancer
Narratives
Peer support
Internet
Abstract ID: 157
Development Of An Optical Ultrasound Sensor For Photoacoustic Imaging Of Melanoma
Author List
1. Additional Author: Ralph Peterson
2. Additional Author: Bailin Zhang
3. Additional Author: Heather Klug-De Santiago
4. Presenting Author: Jing Yong Ye
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Melanoma, the deadliest form of skin cancer, has the most rapidly rising cancer incidence in the United States.
Unfortunately, current clinical practice requires invasive excisional biopsies to determine lesion depth and for melanoma
diagnosis. Although great effort has been made to develop noninvasive melanoma imaging technologies, a number of
serious limitations still exist. Epithelial illumination and confocal scanning laser microscopy techniques have insufficient
penetration depth to measure melanoma thickness due to strong tissue-induced light scattering. High-frequency sonography
provides good penetration depth, but thickness of the melanoma cannot be obtained directly because the image contrast of
melanoma over normal tissues is low.
Methods
To overcome the limitations in current imaging techniques, we are developing a new functional photoacoustic microscopy
(fPAM) system for sensitive, high-resolution detection of skin melanoma. fPAM has recently emerged as a noninvasive in
vivo imaging modality with an improved imaging depth compared with other optical imaging modalities. However, current
fPAM faces several critical challenging problems due to the use of conventional piezoelectric ultrasound transducers. We
are developing a novel optoacoustic sensor to replace the piezoelectric transducer for fPAM based on a patented
technology.
Results
We have designed and fabricated an optoacoustic sensor using a Photonic Crystal structure in a Total-Internal-Reflection
configuration (PC-TIR). In contrast to a conventional Fabryâ€“PÃ©rot etalon, the unique PC-TIR sensor creates a novel
open micro-cavity, allowing the sensor layer to be directly exposed to the photoacoustic signals from tissues without
attenuation by intervening structures. More importantly, the open configuration makes it possible to use materials with high
responsivity to ultrasound signals as cavity media while maintaining a high-finesse cavity. The photonic crystal structure is
composed of five alternative layers of two different dielectric materials (titania and silica). The titania and silica layers
have a designed thickness of 89.8 and 307.2 nm, respectively, and are fabricated with electron-beam physical vapor
deposition. For the cavity layer of the PC-TIR sensor, we are experimenting with different materials such as Poly(methyl
methacrylate), Polystyrene, and Polyethylene, as well as a thin layer of silica, in order to optimize the sensitivity of the
sensor to ultrasound signals. We obtained sensitive responses from the PC-TIR sensor when an ultrasound transducer is
used to generate high-frequency ultrasonic signals as a test source.
Conclusion
A novel optoacoustic sensor has been designed and fabricated to be used as a critical component for constructing an fPAM
system for noninvasive in vivo imaging of melanoma.
Financial Disclosure (Jing Yong Ye)
No
FDA Disclosure
Cleared:Yes
Keywords
Photoacoustic imaging
Optoacoustic sensor
Photonic Crystal Structure
Melanoma
Abstract ID: 158
Crosstalk Between Androgen And Hedgehog Signaling Pathways Promotes The Development Of Androgen
Independent Prostate Cancer
Author List
1. Presenting Author: Janice Deng
2. Additional Author: Pramod Gowda
3. Additional Author: Junhua Yang
4. Additional Author: Sweta Mishra
5. Additional Author: Shu Lin
6. Additional Author: Luzhe Sun
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Increased hedgehog (Hh) signaling was observed in multiple carcinomas, including prostate cancer. However, the interplay
between androgen and Hh signaling pathways in hormone therapy resistant AIPC (androgen-independent prostate cancer)
is less defined.
Methods
Androgen receptor (AR) and Hh pathway components (Shh, Ptch, Smo and Gli1/2) were examined with RT-qPCR and
Western blot for gene expression in androgen-dependent and androgen-independent prostate cancer cell lines, normal
murine prostates, and CWR22 xenografts under androgen deprivation or treatments with agonist or antagonist of both
pathways. Promoter-luciferase assays were used for transcriptional activity of the two pathways as a function of down- or
up-regulation of androgen or Hh signaling activity through manipulation of gene expression.
Results
Androgen depletions for prostate cancer cells or castration for normal and tumor xenograft mice, led to increased
expressions of AR and Hh signaling components with increased transcriptional activities of Hh signaling pathway, but
decreased AR transcriptional activity, in comparison with androgen-dependent prostate cancer (ADPC) or non-castrated
mice. Consistently, AR inhibitors or AR knockdown upregulated Hh signaling, while androgen agonist and overexpression
of AR decreased Hh signaling in AIPC cells. On the other hand, Gli1 knockdown led to increased AR expression and
transcriptional activity. Conversely, overexpression of Gli1 in ADPC cells reduced AR expression and activity. Finally,
blockade of Hh signaling with a Smo inhibitor significantly inhibited the emergence of AIPC from ADPC upon androgen
deprivation.
Conclusion
Hh signaling activity is highly upregulated during androgen deprivation. Hh and androgen pathways appear to negatively
regulate each other in prostate cancer cells. The inhibition of the development of AIPC by the Smo inhibitor suggests that
Hh pathway activity contributes to the development of AIPC, and its inhibitors may be a novel set of drugs for the
prevention of AIPC during hormone therapy.
Financial Disclosure (Janice Deng)
No
FDA Disclosure
Cleared:Yes
Keywords
hedgehog signaling
androgen independent prostate cancer
androgen receptor
androgen
Abstract ID: 159
Evolutionarily Repurposed Networks Reveal The Well-Known Antifungal Drug Thiabendazole To Be A Novel
Vascular Disrupting Agent
Author List
1. Presenting Author: Hye Ji Cha
2. Additional Author: Michelle Byrom
3. Additional Author: Paul Mead
4. Additional Author: Andrew Ellington
5. Additional Author: John Wallingford
6. Additional Author: Edward Marcotte
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In the course of systematically identifying genetic modules that are repurposed during the course of evolution (phenologs),
we discovered a pathway that was both relevant to maintaining of yeast cell walls in response to stress and at the same time
responsible for regulating angiogenesis in vertebrates (1). Because the vascular network supplies oxygen and nutrients to
cancer cells as well as to normal cells, the vasculature is thus considered to be a major therapeutic target for drug
development.
Methods
We reasoned that by analyzing this particular module, we might identify small molecules targeting the yeast pathway that
also act as angiogenesis inhibitors suitable for chemotherapy (2). By computationally mining available large-scale
chemical sensitivity datasets, candidate compounds were prioritized based upon their measured synthetic genetic
interactions with yeast genes, using clustering algorithms to identify those compounds with genetic interaction profiles
most similar to that of lovastatin. This strategy led to the finding that thiabendazole, an orally available antifungal drug in
clinical use for 40 years, also potently inhibits angiogenesis.
Results
TBZ treatment severely impaired angiogenesis in the frog, Xenopus, and in a dose-dependent manner in human cells
(HUVECs). Moreover, in vivo time-lapse imaging revealed that thiabendazole reversibly disassembles newly established
blood vessels, marking it as vascular disrupting agent (VDA) and thus as a potential complementary therapeutic for use in
combination with current anti-angiogenic therapies. The effect of TBZ on endothelial cells suggests that vascular
disruption by TBZ resulted from reduced tubulin levels and hyper-active Rho signaling. Importantly, we also show that
thiabendazole slows tumor growth and decreases vascular density in preclinical fibrosarcoma xenografts. Notably, a TBZ
dose for these experiments was close to the U.S. Food and Drug Administration-approved maximum recommended daily
dose in humans, so the prospects are excellent for human chemotherapeutic use of TBZ.
Conclusion
In sum, an analysis of evolutionary repurposing of a genetic module shared from yeast to humans has led directly to the
discovery that an orally available drug, thiabendazole, already FDA approved for clinical use in humans, also acts as an
angiogenesis inhibitor and vascular disrupting agent. Moreover, these data establish TBZ as the only VDA currently
approved for human use (albeit for a different purpose). With more than 40 years of human use, the low cost and generic
availability of TBZ make it a compelling candidate for translation into the clinic as a VDA. 1. McGary et al., PNAS, 2010.
2. Cha et al., PLoS Biology, 2012.
Financial Disclosure (Hye Ji Cha)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 160
In Vitro Studies Of Salinomycin In Pediatric Gliomas
Author List
1. Presenting Author: Emily Moses
2. Additional Author: Judy Chang
3. Additional Author: Gail Tomlinson
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Brain tumors are the most prevalent childhood solid tumors. In the low-grade astrocytomas complete surgical resection has
achieved over 90% five-year survival rate. In contrast, the aggressive anaplastic astrocytoma high-grade 3 and the fast
growing glioblastoma multiforme high-grade 4 are often refractory to standard therapies; the majority of these patients at
presentation are beyond cure by surgery and/or radiotherapy. Moreover children who survive can develop debilitating
neurocognitive sequelae that greatly affect their quality of life, indicating a need for improved and novel therapies.
Salinomycin, an antibiotic potassium ionophore, has been shown to be highly effective against breast cancer stem cells and
other malignancies; however, its potential use has not been studied in childhood astrocytomas. The objective of this
investigation is to determine whether salinomycin will be effective in eradicating growth of brain cancer cells in a
pre-clinical setting.
Methods
We undertook in vitro analyses on the effect of salinomycin on three pediatric glioma cell lines, Res186, UW479 (provided
by Dr. John Silber, University of Washington), and SF188 (from Dr. Daphne Haas-Kogan, UCSF). First, cellular viability
was determined for these cell lines. The ability of the cells to form colonies in soft agar, programmed cell death, and
cell-cycle distribution in the presence of salinomycin were then measured. Finally, the effect on the stem-like cell
component was measured using surrogate cancer stem cell markers. To evaluate statistical significance we performed
unpaired Studentâ€™s t test and p values <0.05 were used as cut off for significance.
Results
Our results indicated that salinomycin was able to inhibit cellular viability in a dose-dependent manner. The soft-agar
anchorage independent growth assay showed salinomycin inhibition of colony formation. We demonstrated that the
cytotoxicity was a consequence of apoptosis. A decrease in the number of cycling cells (S-phase) was observed in the cells
treated with salinomycin. Furthermore, ~95% reduction in the glioma stem cells of SF188, read-out as CD133+, and an
impairment in the ability to form spheres (read-out as self-renewal) was observed.
Conclusion
Our data demonstrated that salinomycin could be exploited for the treatment of pediatric gliomas.
Financial Disclosure (Emily Moses)
No
FDA Disclosure
Cleared:Yes
Keywords
Pediatric Gliomas
Salinomycin
Drug Development
Translational Research
Abstract ID: 161
Preventative Health Screen Barriers And Houstonians With Disabilities
Author List
1. Presenting Author: Kayla Karvonen
2. Additional Author: Margaret Nosek
3. Additional Author: Edward Elms
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Comparison of Frequency of Helath Screens Between People with Disabilities and People Without Disabi
Summary
Introduction
 
As of 2000, 20% of the United States reported a disability in the U.S. Census and this number only continues to grow
(Waldrop & Stern 2003). The disability community is vastly diverse and thus the needs of each individual vary greatly.
Preventative health care is important for the general population including people with disabilities. 
Previous research has shown that people with disabilities have a lower incidence of some preventative health screens than
people without disabilities (Nosek & Howland, 1997). Many different barriers have been identified. For example, women
with mobility impairments are less likely to receive preventative health care screens in some studies. Interestingly enough,
people with mobility impairments were also more likely to have a constant source of healthcare (Iezzoni, McCarthy, Davis,
& Siebens, 2000). 
In the present research study, we sought to identify barriers that Houstonians with disabilities encounter that prevent them
from receiving recommended preventative health screens.
Methods
 
Twenty-six men and women aged 31 to 90 years old were recruited from the Metropolitan Multi-service Center in
Houston, Texas during weekday mornings to participate in the 15 minute structured interview. To be eligible individuals
had to be from Houston and self-identify as having a disability. The interviews were recorded and partially transcribed. 
Results
 
All participants had seen a health care professional within the last year. Less than half (46.7%) of women knew the correct
age recommendation for mammograms and Pap tests within 10 years. No women knew the correct age recommendation for
bone mass density measures, although 57% guessed a younger age, erring on a less harmful side. The average guess for the
age recommendation for PSA tests was 49.4 years. 
Most women received a Pap smear (93.3%) and mammogram (86.7%), and most men had a PSA test (66.7%), similar to
Texas and nationwide values for people without disabilities from the Behavioral Risk Factor Surveillance Systemâ€™s
Prevalence and Trends Data from the Center for Disease Control in 2010. Clinical breast exam (86.7%) and BMD Screen
(60%) rates were also high. 
Conclusion
 
The disability community interviewed has insufficient knowledge of recommended screens by U.S. Preventative Services
Task Force but the majority of the community is up-to-date with their screening. For those who did not receive a screen
when they were of appropriate age, the most common barrier was no recommendation from a health care professional. The
study was limited by a small sample size and a skewed demographic distribution.
Financial Disclosure (Kayla Karvonen)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 162
Assessment Of Lymph Node Status In Prostate Cancer By Antibody-Based Multimodal Imaging
Author List
1. Presenting Author: Ali Azhdarinia
2. Additional Author: Barrett Harvey
3. Additional Author: Sukhen Ghosh
4. Additional Author: Kenneth Pinkston
5. Additional Author: Holly Robinson
6. Additional Author: Pradip Ghosh
7. Additional Author: Karina Vazquez-Arreguin
8. Additional Author: Nathaniel Wilganowski
9. Additional Author: Mary Hall
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Currently, nodal staging of prostate cancer (PCa) is performed after lymph node (LN) biopsy and dissection for subsequent
pathologic examination. Due to the lack of sensitive diagnostic methods for assessing tumor status in LNs, aggressive
surgical interventions such as extended pelvic LN dissection are employed and often result in debilitating surgical
morbidities. Identification of tumor-associated antigens, such as epithelial cell adhesion molecule (EpCAM), enables the
use of targeted molecular imaging agents to non-invasively assess LN status in PCa. Here, we describe the development
and characterization of antibodies (mAbs) and mAb fragments that target EpCAM using an integrated multimodal
approach with Positron Emission Tomography (PET) and near-infrared fluorescence (NIRF) imaging.
Methods
High affinity anti-EpCAM antibodies were generated by immunizing BALB/c mice with either recombinant human
EpCAM/Fc or with breast cancer cells that highly express the antigen (MCF7). Dual conjugates were synthesized by
random or site-specific addition of a chelating agent (DOTA) and a NIR dye (IRDye 800), and immunoreactivity was
assessed by ELISA and flow cytometry. The agents were radiolabeled with 64Cu and purified by size
exclusion. Chelator/protein (C/P) and dye/protein (D/P) ratios were determined for each conjugate. Mice were implanted
orthotopically with PC3-DsRed cells and used for PET/NIRF imaging studies.
Results
In vitro assays showed that modification of full-length mAbs with DOTA and IRDye 800 with conventional NHS
chemistry led to a greater reduction in immunoreactivity compared to thiol-based coupling. Varying C/P and D/P ratios
were obtained and impacted 64Cu labeling yields (60-80%) and immunoreactivity, respectively. Multimodal
imaging revealed delineation of the primary tumor and tumor-positive LNs by both PET and NIR fluorescence imaging
and demonstrated concordance between the PET and NIRF imaging approaches. mAb fragments contained site-directed
conjugation sites and thus showed excellent retention of immunoreactivity after modification. 64Cu labeling
conditions negatively impacted immunoreactivity of mAb fragments, thus further optimization of the labeling process is
required.
Conclusion
Dual-labeled mAbs can be prepared with different synthesis strategies and used for detection of cancer positive LNs. PET
imaging can provide whole body staging while NIRF imaging can be used to directly correlate PET findings with
registration with surgical, NIRF fields of view.
Financial Disclosure (Ali Azhdarinia)
No
FDA Disclosure
Cleared:Yes
Keywords
EpCAM
multimodal imaging
antibody
dual labeling
Abstract ID: 163
Neurod1 Orchestrates TrkB, Nicotine Acetylcholine Receptors, And NCAM Signaling To Promote Survival And
Metastasis Of Neuroendocrine Lung Cancers
Author List
1. Presenting Author: Jihan Osborne
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 02:55 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The neuroendocrine lung tumors, small cell lung cancer (SCLC), large cell neuroendocrine carcinomas (LCNEC), and
typical and atypical carcinoids are among the most aggressive lung cancers. These tumors correlate highly with nicotine
exposure and are particularly devastating as patients often have multiple metastases at time of diagnosis; in addition,
survival rates are extremely low. Understanding the molecular mechanisms that drive pathogenesis and metastasis in these
tumors is key to better targeted therapies. The developmental basic helix-loop-helix transcription factor neurogenic
differentiation 1 (NeuroD1), which is usually restricted to endocrine pancreas and hippocampal neurons in the adult, is
anomalously expressed in neuroendocrine lung tumors. This factor acts as a regulatory hub to secure cross-talk among
growth-inducing signaling pathways.
Methods
Results
Microarray analysis of 130 lung cancer cell lines, revealed that 24 SCLCs and 9 NSCLC-NEs, expressed a relatively high
level of NeuroD1 mRNA. Reduction of NeuroD1 expression via stable knockdown with shRNA impairs the ability of
neuroendocrine lung cancer cells to form tumors and metastasize in mice. Nicotine, a major lung cancer risk factor, induces
NeuroD1 expression in non-transformed lung epithelial cells via down-regulation of p53. Stable knockdown of p53 induces
NeuroD1. NeuroD1 confers aggressive behavior on neuroendocrine tumors primarily through its downstream target, the
receptor tyrosine kinase, TrkB. Inhibiting TrkB expression or activity limits cell survival and xenograft tumor growth.
Using chromatin immunoprecipitation we find that, in addition to TrkB, subunits of the nicotinic acetylcholine receptor
(nAChR) gene cluster of CHRNA5/A3/B4 are also direct targets of NeuroD1. Like NeuroD1, TrkB also regulates the
expression of several of these nAChRs, adding another level of complexity.
Conclusion
Together NeuroD1 and TrkB regulate the nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster, suggesting a
novel cooperative mechanism for the regulation of these receptors that thus far have been linked to addiction and lung
cancer susceptibility. Taken together these findings indicate that NeuroD1 and TrkB regulate malignant behavior in a
subset of neuroendocrine lung cancers. Regulation of the gene cluster by NeuroD1 suggests a novel feedback loop that
could arise early in the process of malignant transformation. Based on these results we define mechanisms underlying a
substantial group of neuroendocrine carcinomas and propose a new model of events that occur during the onset of
pathogenesis.
Financial Disclosure (Jihan Osborne)
No
FDA Disclosure
Cleared:Yes
Keywords
small cell lung cancer
NeuroD1
nicotine
None
Abstract ID: 165
Histone H3K56 Hyper-acetylation Blocks Break Induced Replication
Author List
1. Presenting Author: Jun Che
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Histone H3K56 acetylation is a marker for newly-synthesized histones. The dynamics of H3K56ac is critical for cells to
maintain genome stability. While acetylated H3K56 helps deposition of histones onto DNA during S-phase, the acetylation
has to be removed after histone deposition. Without acetylation or de-acetylation causes genome instability. However, the
mechasnims how H3K56ac affects genome instablility is poorly understood. In Saccharomyces cerevisiae, histone H3K56
is acetylated by Rtt109 while deactylated by Hst3 and Hst4.
Methods
Our methods including yeast genetics, Southern Blot, Western Blot, FACS and molecular coloning.
Results
We found in hst3hst4âˆ† cells, genome instability increase dramatically. This is even worse when combine with DNA
damage checkpoint mutants. We also found that hst3hst4âˆ† cells are defective in break induced replication (BIR), a major
type of homologous recombination, during which a broken DNA end find its homologous sequence and copy the DNA
sequence all the way to the end of a chromosome. This defect causes persistent DNA damage checkpoint activation in a
HO endonuclease induced break. Interestingly, the defect in BIR can be rescued by further deleting Asf1 or Rtt109, which
are responsible for H3K56 acetylation. This indicates it is hyper-acetylation of H3K56 causes BIR defect. During
replication, collapsed replication fork may restart by BIR pathway in principle. In consistent with this notion, we found that
hst3hst4âˆ† cells are sensitive to methyl methanesulfonate (MMS) but not sensitive to Hydroxyurea (HU) treatment. It is
known that MMS can block replication and cause fork collapses while HU only slow down replication forks.
Conclusion
In conclusion, hst3hst4âˆ† cell sensitivity to MMS might be due its defect in BIR. Defect in BIR might be a potential
mechanism for the genome instability in hst3hst4âˆ† cells.
Financial Disclosure (Jun Che)
No
FDA Disclosure
Cleared:Yes
Keywords
H3K56
hyper-acetylation
Break induced replication
Replication fork collapse
Abstract ID: 167
Motivation, Exercise And Stress In Breast Cancer Survivors
Author List
1. Presenting Author: Dorothy Long Parma
2. Additional Author: Brandi Cuevas
3. Additional Author: Rose Trevino
4. Additional Author: Daniel Hughes
5. Additional Author: Amelie Ramirez
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Among many benefits of physical activity (PA) for breast cancer survivors is a link to reduced cancer recurrence risk.
However, many survivors who were previously inactive stay inactive, and those who were active do not return to their
previous activity level. The decision to engage in exercise is linked to many factors, including current body mass index
(BMI), stress levels, motivational profile, and exercise history. We performed a cross-sectional analysis to investigate
associations between stress (self-reported and measured with salivary cortisol), motivational profiles, exercise history,
current BMI and current PA in 94 post-treatment breast cancer survivors voluntarily enrolled in a six-month exercise
program.
Methods
After providing informed consent, participants had height and weight measured and completed a questionnaire packet
containing demographic information, medical history, Life Time of Physical Activity Questionnaire, International Physical
Activity Questionnaire (IPAQ), Medical Outcomes Short Form SF-36Â® Mental Component Scale (MCS), Perceived
Stress Scale (PSS), and Apter Motivational Style Profile (AMSP). After completing the packet, participants were given 10
vials to collect salivary cortisol at five different time-points over two consecutive days. Mean cortisol levels and mean
slope were averaged for both days. Descriptive and correlational analyses were conducted on BMI, stress, motivation,
exercise history, and current PA.
Results
Participants averaged 56.2 years of age and were overweight (mean BMI=28.7, SD=6.7). Participants reported being
historically active (mean activity MET hours/week=14.2) and active in total current PA (average total activity 39.2 MET
hours/week); had high stress levels (mean PSS=33.6; SD=4.5); and low functionality levels (SF-36Â® Mean MCS=44.4,
SD=8.8). Participant motivational profile included being goal- oriented, conformist, sympathetic, and focused on others.
Current PA was negatively associated with salivary cortisol level (r=-0.28, p=0.01); association approached significance
with BMI (r=-0.19, p=0.07) in the expected direction. Mean salivary cortisol was associated with BMI (r=0.21, p=0.05).
Perceived stress (PSS) was not associated with salivary cortisol, but was negatively associated with SF-36Â® MCS score.
Only the conforming motivational profile was associated with any variable (MCS score) indicating higher conforming
participants had better mental functioning.
Conclusion
This is the first examination of data from an extensive six-month exercise intervention in post-treatment breast cancer
survivors. Decreased current activity suggests more stress as measured by salivary cortisol. Conforming motivational
profile indicates less overall stress and better MCS outcome. The results verify that exercise association with stress and
motivation are complicated and require more investigation; further examination will be done over the course of the
intervention.
Financial Disclosure (Dorothy Long Parma)
No
FDA Disclosure
Cleared:Yes
Keywords
breast cancer survivor
motivation
stress
physical activity
Abstract ID: 168
Inhibition Of Hedgehog And Androgen Receptor Signaling Pathways Produced Synergistic Suppression Of
Androgen Independent Prostate Cancer Progression
Author List
1. Presenting Author: Pramod Gowda
2. Additional Author: Janice Deng
3. Additional Author: Sweta Mishra
4. Additional Author: Luzhe Sun
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Prostate cancer (PCa) is the second most common cause of death from cancer and the leading cancer diagnosed in the US
men. Approximately 1 in 6 American men will be diagnosed with prostate cancer during his lifetime. Estimated new cases
and deaths from prostate cancer in the United States for 2012 include: 241,740 new cases and 28,710 deaths. Initial
treatment for metastatic PCa involves androgen ablation therapy, which causes regression of androgen-dependent tumors.
However they all eventually relapse resulting in recurrent androgen independent prostate cancer (AIPC)
Methods
This study aims at assessing the role of Hedgehog (Hh) and Androgen receptor (AR) signaling in the development of
AIPC. Quantitative RT-PCR analysis was performed for AIPC cells in vitro and for AIPC xenograft after castration, to
assess the levels of Hh and AR signaling components. Hh inhibitors, LDE225 (Novartis) and Cyclopamine, and Androgen
receptor inhibitor Pyrvinium pamoate were tested individually and in combination to assess the suppression of AIPC
progression both in vitro and in vivo. AR-responsive and Gli-responsive promoter-luciferase assay and MTT assay were
used for in vitro studies. Intraperitoneal administration of drugs and bioluminescence imaging for monitoring orthotopic
tumors in mice were used to study the effect of drugs on the growth of AIPC in vivo.
Results
We demonstrate that androgen deprivation leads to increase in Hedgehog (Hh) signaling components in the AIPC cells in
vitro and in vivo. AIPC cells also show increased sensitivity to low concentrations of androgen, suggesting increased
androgen receptor expression. Together, these results suggest that increased Hh signaling and androgen receptor expression
in the absence of androgen agonist plays an important role in the development and progression of AIPC. Our results show
that inhibiting either Hh or androgen receptor signaling pathway individually was not effective in preventing AIPC cell
proliferation in vitro as well as in inhibiting xenograft tumor growth in mice. In contrast, combination of an Hh pathway
inhibitor with an androgen receptor inhibitor synergistically suppressed the growth of AIPC cells in vitro as assessed by
MTT assay and reduced tumor burden in a mouse xenograft model of AIPC as compared to individual treatments.
Conclusion
Upregulated Hh signaling and AR expression mediates development and progression of AIPC. Combined inhibition of Hh
and androgen receptor signaling pathways may be a novel effective therapeutic strategy for the treatment of androgen
independent prostate cancer.
Financial Disclosure (Pramod Gowda)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 169
Tcf3 Promotes Tumor Growth And Progression In Skin
Author List
1. Presenting Author: Jeffrey Howard
2. Additional Author: Timothy Shaver
3. Additional Author: Ajay Rao
4. Additional Author: Gloria Garcia
5. Additional Author: Diep Le
6. Additional Author: Hoang Nguyen
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Recent studies have focused interest on cancer stem or tumor-initiating cells (TICs) as key drivers of malignancy. In many
cases, including squamous cell carcinoma (SCC) of the skin, tumor growth appears to be a â€œcaricatureâ€• of normal
tissue homeostasis, driven by cancer stem cells which resemble normal tissue stem cells. 
Our research focuses on Tcf3, a transcription factor expressed in both normal skin stem cells and squamous cell TICs.
Previous work in our lab has shown that Tcf3 plays an important role in skin stem cell function: ectopic expression of Tcf3
blocks differentiation, while loss of Tcf3 and its paralogue Tcf4 results in a failure of homeostasis and self-renewal. The
fact that Tcf3 is associated with the cancer-like traits of self-renewal and undifferentiation prompted us to examine its role
in skin carcinogenesis. 
Methods
We subjected K14-rtTA; TRE-Tcf3 (skin-specific, tetracycline-inducible Tcf3 transgenic mice) to a two-step
DMBA/TPA tumorigenesis protocol in the presence or absence of doxycycline in order to observe the effects of Tcf3
overexpression on tumor multiplicity, growth, and progression.
Results
Tcf3 overexpression increased the number and growth rate of chemically induced tumors in mouse skin and increased
progression of benign papillomas into malignant SCCs.
Conclusion
Our initial findings suggest that Tcf3 expression is a strong promoter of skin tumorigenesis in vivo; however,
the exact mechanism underlying this effect is unclear. We are currently undertaking studies to elucidate the mechanism by
which Tcf3 promotes tumors, as well as to evaluate the significance of Tcf3 in human disease.
Financial Disclosure (Jeffrey Howard)
No
FDA Disclosure
Cleared:Yes
Keywords
Tcf transcription factors
non-melanoma skin cancer
Tcf7l1
chemical tumorigenesis
Abstract ID: 171
Multimodal Tomography For Localization Of BMP2 Transduced Cells For Spine Fusion
Author List
1. Presenting Author: Yujie Lu
2. Additional Author: LaShan Simpson
3. Additional Author: ZaWaunyka Lazard
4. Additional Author: Elizabeth Olmsted-Davis
5. Additional Author: Alan Davis
6. Additional Author: Jennifer West
8. Additional Author: Chinmay Darne
9. Additional Author: Mary Hall
10. Additional Author: Holly Robinson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
CPRIT2012_Yujie.jpg
Summary
Introduction
Bone morphogenetic proteins (BMPs) are well known for their osteoinductive potential, yet effective clinical utilization for
bone repair using recombinant BMP2 protein suffers from a short-lived bolus effect. Recently, Davis and coworkers
(Tissue Engineering Part A, 16, 3727-3736, 2010)developed a cell-based gene therapy approach that utilizes virally
transduced fibroblasts encapsulated in poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres to enable
sustained BMP2 delivery, protection from host immune response, and localized placement for bone fusion. However,
assessment of implantation position and longitudinal evaluation of BMP2 expression and therapeutic response in vivo
requires three-dimensional tomography.
Methods
Recently, we developed a tri-modality (NIRF(Near-infrared Fluorescence)/PET/CT) tomography system by integrating
time-dependent, optical components and a miniaturized NIR intensified camera into a Siemens Inveon scanner to perform
NIRF imaging (785/830 nm) of BMP2 transduced fibroblasts encapsulated in AlexaFluor790-labeled PEGDA hydrogel
microspheres after injection in the right paraspinous muscle of a mouse. NIRF/CT imaging was performed at day 15
post-injection. CT imaging was performed using high spatial resolution mode to acquire the imaging information of new
bone due to its low contrast compared to surrounding tissues. Subsequent standard CT scanning and NIRF tomography
were performed to obtain the entire mouse surface information and image the fluorescence photon distribution on the
mouse surface at four different projections. The fluorescent photon distribution was mapped onto the CT-derived surface
using a pinhole camera model. The volumetric mesh consisting of about 13,000 discretized points was generated using the
CT volume for NIRF tomography. A linear reconstruction algorithm with a high-order simplified spherical harmonics
approximation was developed to realize NIRF tomography.
Results
Although new small bone has low contrast in CT images, its morphological information can be acquired from the CT
images in high spatial resolution mode. We compared the CT images with NIRF tomography. New bone formation
observed in CT images was also visualized in NIRF tomography, and consistent with the therapeutic response to the
implant.
Conclusion
It is difficult to image new bone at its early stage using anatomical imaging modalities due to the physical limit, which
obstructs early evaluation of BMP2 expression and therapeutic response. The preliminary results demonstrate the potential
of multimodality NIRF tomography in this application.
Financial Disclosure (Yujie Lu)
No
FDA Disclosure
Cleared:Yes
Keywords
Multimodaltiy small animal imaging
Optical tomography
Reconstruction algorithm
Spine fusion
Abstract ID: 172
Novel Mouse Models To Investigate The Molecular Pathogenesis Of Metastatic Osteosarcoma
Author List
1. Additional Author: Shuying Zhao
2. Additional Author: Lyazat Kurenbekova
3. Additional Author: Tsz-Kwong Man
4. Additional Author: Ching Lau
5. Additional Author: Pulivarthi Rao
7. Presenting Author: Jason Yustein
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Osteosarcoma (OS) is the primary bone tumor in the pediatric population with the main determinant for patient prognosis
being the presence of metastatic disease. Approximately 20-25% of patients will present with metastatic osteosarcoma.
Patients with metastatic disease have long-term survival rates often <20%. We hypothesize that the molecular
pathogenesis of metastatic osteosarcoma is different from localized disease. We intend this work to provide a relevant,
endogenous model of metastatic OS that can be utilized to advance our understanding of the molecular pathogenesis of the
disease, insights into novel therapeutic targets and provide a pre-clinical model for investigating the efficacy of novel
therapies.
Methods
We have developed a tissue-specific alteration of the p53 status by using osteoblast specific Cre-recombinase expressing
mice to generate progeny that spontaneously form endogenous osteosarcomas. Through the use of a mutated, gain of
function form of p53, shown previously to be associated with metastatic disease, we have developed a novel
immunocompetent model that significantly enhances the endogenous development of metastatic OS.
Results
Tumor analysis has revealed genetic insights in the metastatic progression of osteosarcoma. These include the significant
downregulation of Wnt-signaling inhibitors, such as NKD2, APCDD1 and WNT5A in the metastatic tumors. Functional
studies have determined that overexpression of NKD2 in metastatic mouse OS cell lines leads to a significant delay in
primary tumor growth and reduced development of metastatic lung lesions upon transplantation into immunodeficient
mice. Furthermore, we also noted downregulation of NKD2 in several human OS metastatic cell lines. Possible
NKD2-dependent functions include regulation of not only the Wnt signaling pathway, but also blood vessel formation,
regulation of cell migration and cell adhesion. We have also observed the dysregulation of several critical microRNAs in
metastatic OS, including the upregulation of mir-130b in the metastatic lesions. This particular microRNA has recently
been shown to have clinical correlation in Ewingâ€™s sarcoma, with higher levels of tumor mir-130b having a
significantly poorer outcome. We are actively pursuing the role of this (and other) microRNA(s) in the molecular
pathogenesis of metastatic osteosarcoma.
Conclusion
This novel model has enabled valuable molecular insights into the development and progression of metastatic OS that can
lead to the identification of novel therapeutic targets.
Financial Disclosure (Jason Yustein)
No
FDA Disclosure
Cleared:Yes
Keywords
Osteosarcoma
Metastasis
Mouse models
None
Abstract ID: 173
Cervical Cancer-Free Texas: A Collaborative Effort To Eliminate Cervical Cancer Among Texans
Author List
1. Presenting Author: Erica Lipizzi
2. Additional Author: Lara Savas
3. Additional Author: Maria Fernandez
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cervical Cancer-Free Texas (CCFTx) is a statewide initiative to eliminate or substantially reduce cervical cancer in Texas.
Women in Texas have higher cervical cancer incidence and mortality rates compared with women in the U.S. overall, and
rates for Hispanics and African Americans are higher than for non-Hispanic whites. Compared with the U.S., the HPV
vaccination rate in Texas is lower for initiation of vaccination and completion of the vaccine series.
Methods
Led by researchers at The University of Texas School of Public Health, CCFTx is forming a statewide network of partners
and coordinating efforts to increase guideline-recommended cervical cancer screening and HPV vaccination. Programs are
being developed to address gaps in cervical cancer prevention, reduce disparities, and create sustainable change in health
systems and policies in Texas.
Results
CCFTx formed a partnership with the Cancer Prevention Research Institute of Texas and established the Texas Cervical
Cancer Coalition. This statewide coalition brings together leaders of 19 CPRIT-funded programs that provide cervical
cancer screening and HPV vaccination services to underserved women in Texas. As part of Cervical Cancer Awareness
month, in 2012, CCFTx hosted Houstonâ€™s first cervical cancer summit in partnership with MD Andersonâ€™s
Cervical Comprehensive Cancer Control Workgroup, Houston Community College, and the Texas regional Community
Network Program, Latinos Contra El Cancer. The summit convened leading stakeholders in cervical cancer prevention to
raise awareness, review evidence-based practices, and build a more coordinated approach to reducing cervical cancer in the
Houston area. In April 2012, CCFTx collaborated with Latinos Contra El Cancer and the Cancer Prevention and Control
Research Network, Latinos in a Network for Cancer Control, to award mini-grants to community-based organizations to
implement evidence-based strategies or expand programs that address cervical cancer control and prevention in Texas. To
increase HPV vaccination in youth, a new initiative is being planned with the University of Texas Prevention Research
Center and the Houston Independent School District to incorporate education about HPV into evidence-based sexual health
curricula.
Conclusion
CCFTxâ€™s network of partners focused on cervical cancer prevention and control provides an infrastructure through
which evidence-based programs that increase cervical cancer prevention are identified or developed, disseminated, and
sustained. CCFTx will continue to collaborate with partners to develop educational campaigns, facilitate the sharing of
resources, and conduct outreach efforts to reduce barriers and increase access to screening and HPV vaccination
throughout the state.
Financial Disclosure (Erica Lipizzi)
No
FDA Disclosure
Cleared:Yes
Keywords
cervical cancer
HPV
immunization
female
Abstract ID: 174
Synthetic DNA Nanostructures As Immune Boosters For Vaccines
Author List
1. Presenting Author: Alexey Koyfman
2. Additional Author: Chenxiang Lin
3. Additional Author: Boxue Ma
4. Additional Author: William Shih
5. Additional Author: Wah Chiu
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Nucleic acids are promising in bionanotechnology due to their defined length, unique base pair recognition capabilities,
and amenability for base and backbone modifications. Commercially available synthetic oligodeoxynucleotides (ODN)
containing unmethylated CpG motifs characteristic of bacterial DNA are a promising class of adjuvants (booster of the
immune response) that target innate immune cells to modulate adaptive immune responses to vaccine and
immunotherapeutic agents. While simple physical mixing of the CpG-ODN with antigens was shown to stimulate specific
immune responses, close spatial proximity of these adjuvants to antigens have previously been shown to boost immune
responses in animal models. Effective vaccination with antigens employing appropriate adjuvants is essential for successful
immunization. We plan to attach synthetic polypeptides that are model antigens to a 3D DNA architecture containing
specific sequence motifs acting as an adjuvant. The spatial proximity of CpG sequence motifs to antigens, as well as
antigen occurrence and orientation within the nanostructure can be controlled and characterized. We are using electron
cryo-microscopy for determining the structure of a compact 3D DNA origami. This rigid DNA structure design could be
very well suited for optimization with attached peptides. This project aims to improve the efficacy and reduce the cost of
vaccination by using DNA based adjuvant and rationally designing the architecture of the vaccine molecule.
Methods
We used electron cryo microscopy (cryo-EM) to determine the structure of the 4.4 MDa DNA origami structure. The 48
helices in this origami structure self assembles from a large viral DNA scaffold strand and multiple synthetic
complementary DNA strands. Cryo-EM is an emerging structural tool to obtain near atomic resolution structure of
molecular machines in solution state without invoking crystallography.
Results
Our cryo-EM reconstruction was in agreement with the nanoscaffold design. The cryo-EM model shows that a DNA brick
is twisted clockwise due to the helical nature of DNA. Some DNA strands in the brick are designed to be longer then
others. This is visible in the cryo-EM model.
Conclusion
One of the goals of this project is to obtain ~4 Ã… 3-D structural resolution comparable to the resolution of chaperonins
and viruses. At this resolution the polypeptide backbone and bulky side chain can be resolved. Our results show that
cryo-EM can be used as a structure characterization platform of peptides conjugated DNA nanostructure.
Financial Disclosure (Alexey Koyfman)
No
FDA Disclosure
Cleared:Yes
Keywords
Synthetic DNA nanostructures
DNA origami
cryo-EM
None
Abstract ID: 175
Targeting STAT3 Pathway By Static Inhibits The Neuroblastoma Cancer Stem Cell-like Cells
Author List
1. Presenting Author: Saurabh Agarwal
2. Additional Author: Danielle Hsu
3. Additional Author: Zaowen Chen
4. Additional Author: Eugene Kim
5. Additional Author: Jason Shohet
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
We have recently defined a highly tumorigenic novel sub-population of neuroblastoma cells based on their surface
expression of CD114 (G-CSFR). These cells have many properties of Cancer Stem Cells (CSCs) based on their
self-renewal, differentiation and lineage restricted tumorigenicity and we find them in all NB cell lines, xenografts and
primary tumor biopsy specimens. As STAT3 activation is a canonical downstream event of G-CSFR ligand and is also
vital to maintenance of cancer stem cell populations, we hypothesized that blocking the STAT3 pathway by specific
inhibitors can functionally inhibit the cancer stem cell-like neuroblastoma sub-population.
Methods
We used specific low density pathway specific arrays to indentify the key genes involved in our novel stem-cell like
population. A STAT3 activation reporter construct containing eGFP gene cloned downstream of a four M67 responsive
promoter was used to transduce neuroblastoma cells. NB cells were treated with different concentrations of G-CSF and
Stattic for different time points and analyzed for cell surface expression of CD114 and intracellular phosphorylated STAT3
levels by phospho-flow assay using PE-conjugated anti-CD114 antibody and Pacific Blue-conjugated anti-Stat3 (pY705)
antibodies.
Results
Gene expression analysis showed key neural epithelial, self-renewal and cell-cycle regulator genes associated with
maintenance of pluripotency were upregulated in CD114+ population while neural mesenchymal specific genes in CD114population. Treatment of Neuroblastoma cell lines with G-CSF showed remarkable increase of CD114 population and
activation of STAT3 as detected by GFP expression in a dose and time dependent manner. The addition of Stattic, a
STAT3 inhibitor which prevents phosphorylation and dimerization of STAT3, specifically abrogates the effect of
exogenous G-CSF treatment. Phospho-flow analysis further confirms the activation of STAT3 in response to exogenous
G-CSF treatment by phosphorylation of Tyrosine 705 (Y705) and signaling of G-CSFR (CD114) through STAT3 node,
which also abrogated by Stattic.
Conclusion
The gene expression analysis suggests a neural crest-specific epithelial to mesenchymal transition and that the CD114+
cells display s gene signature of neural ectoderm. Further differentiation of theses â€˜pre-migratoryâ€™ neural crest cells
into migratory neural crest would be consistent with a stem like phenotype of CD114+ cells. The responsiveness of tumor
initiating CD114+ cells to exogenous G-CSF and the signaling mediated by STAT3 pathway is consistent with the role for
STAT3 signaling as a vital signaling node in other cancer stem cell models. Our data suggest a potential clinical role for
STAT3 inhibitors as anticancer stem cell therapy in neuroblastoma.
Financial Disclosure (Saurabh Agarwal)
No
FDA Disclosure
Cleared:Yes
Keywords
Neuroblastoma
STAT3
Stattic
Cancer Stemm Cell
Abstract ID: 176
DNMT3a And IDH2 Act In Synergy In Leukemogensis
Author List
1. Presenting Author: Xiaotian Zhang
2. Additional Author: Mira Jeong
3. Additional Author: Liubin Yang
4. Additional Author: Margaret Goodell
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Cancer has been found bearing unique metabolism signature comparing with normal tissue for long time. Yet the tumor
associated metabolism has long been viewed as the result of carcinogenesis. Whether the onco-metabolites can contribute
to the carcinogenesis process is still unknown. Until recently, unrevealing discoveries have been made on
IDH1/2 (isocitrate dehydrogenase 1/2 ) mutation and its neomorphic function of overproduction of
onco-metabolite 2-HG in acute myeloid leukemia (AML) and low grade glioma, showing excessive 2-HG will cause the
block of DNA methylation and thus drive the increase of stem cell self-renewal. More interestingly, 10-20 % of AML
patients with DNMT3A (de novo DNA methyltransferase 3a) somatic mutation also carry IDH1/2
mutation. Also DNMT3A and IDH1/2 mutation are statistically significantly associated with each other in AML patients.
Because both Dnmt3a knockout and IDH1 mutation knock-in mouse donâ€™t develop overt
hematopoietic malignancies, we thus hypothesize Dnmt3a and IDH1/2 mutation will act
synergistically in leukemogenesis.
Methods
To create the Dnmt3a null; IDH1/2 neomorphic gain-of-function double mutant mouse model, we
had employed a transplantation approach to create IDH2R140Q (one of the abundant IDH2
mutation) overexpressing stem cells with both Dnmt3a knockout (Dnmt3a-/-) and
wide type (Dnmt3a+/+) background by using MSCV transduction. IDH2 WT overexpression in both
Dnmt3a-/- and Dnmt3a+/+ background is used as control group. Stem cells
are then transplanted into lethally irradiated mice. Recipient mice are examined periodically for disease symptoms
Results
About 22-24 weeks after transplantation, transplantable overt myeloid leukemia is observed in
Idh2R140Q ;Dnmt3a-/-recipients. While
Idh2R140Q ; Dnmt3a+/+ recipients do not initiate overt leukemia. Yet in
these recipients, Idh2R140Q overexpression is still sufficient to cause myeloid differentiation
bias. Whatâ€™s more, when leukemic cells from sick animals are plated in vitro to measure their stem cell activity, excess
glutamine in culture can enhance colony forming ability of Idh2R140Q;
Dnmt3a-/- cell. This indicates glutamine taken by cells can enhance the self-renewal of
Idh2R140Q; Dnmt3a-/- stem cells and thus targeting glutamine may
imply future clinical intervention on patients carrying both with DNMT3a and IDH2 mutation.
Conclusion
In summary, our research shows for the first time, Dnmt3a and Idh2 mutation will synergistically
cooperate to initiate leukemia. Transcriptome and metabolomics analysis will be taken to search for the genes and
metabolites with altered expression in Idh2R140Q; Dnmt3a-/- leukemia
to understand the molecular mechanism initiating the leukemia. Our research will provide the insight into the molecular
function of Dnmt3a in leukemogenesis and provides future drug development on patients with both somatic mutations.
Financial Disclosure (Xiaotian Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 177
Trimodality Therapy Completion And Treatment Patterns Of Locally Advanced Esophageal Adenocarcinoma In
An Off-protocol Setting
Author List
1. Presenting Author: Caitlin Murphy
2. Additional Author: Arlene Correa
3. Additional Author: Wayne Hofstetter
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Trimodality therapy with neoadjuvant chemoradiation followed by surgery significantly improves the survival of locally
advanced (clinical stage IIA-III) esophageal cancer patients compared to treatment with surgery alone. This has resulted in
an increased use of neoadjuvant therapy in recent years, yet little is known regarding how this increase has impacted the
utilization of surgery in the treatment of locally advanced disease. Although previous reports of experimental protocols
suggest that 90-95% of patients complete trimodality therapy including a surgical resection, trimodality therapy completion
among adenocarcinoma patients eligible for curative resection has not been evaluated in an off-protocol setting. We sought
to 1) assess the prevalence of trimodality therapy completion among locally advanced esophageal adenocarcinoma patients;
2) describe the incidence and indications for avoiding surgery; and 3) identify factors associated with failure to complete
trimodality therapy.
Methods
We identified 298 patients with locally advanced esophageal adenocarcinoma eligible for trimodality therapy at our
institution. All patients were evaluated in a multidisciplinary setting and considered eligible for curative resection after
initial staging and physiologic assessment. Medically inoperable patients with significant comorbidities were excluded.
Multivariable logistic regression was used to identify factors associated with failure to complete trimodality therapy.
Results
Of 298 trimodality eligible patients, 33% (99/298) did not undergo a surgical resection. The most frequent reason for
eliminating surgery was patient choice (28.3%), followed by distant progression of disease during chemoradiation (24.2%)
and physician preference for surveillance (23.2%). Some patients did not undergo surgery due to decrease in performance
status (17.2%) or treatment related death during chemoradiation (7.1%). Multivariable logistic regression identified older
age (65-70 yrs: OR 2.38, 95% CI 1.01-5.61; â‰¥70 yrs: OR 7.47, 95% CI 3.22-17.31), pre-treatment SUV â‰¥15.8 (OR
4.50, 95% CI 1.90-10.65), and radiation dose â‰¥50.4 Gys (OR 5.60, 95% CI 2.58-12.16) as being significantly
associated with failure to complete trimodality therapy.
Conclusion
Trimodality therapy completion among locally advanced esophageal adenocarcinoma patients in an off-protocol setting is
lower than what has previously been reported in clinical trials. Our findings suggest that a selective approach to surgery is
commonly utilized in clinical practice; the decision to complete trimodality therapy is often made during and/or after
chemoradiation. Further research is needed to understand how the delivery of and failure to complete trimodality therapy
may affect outcome. Identifying clinical predictors of response to chemoradiation may guide the delivery of trimodality
therapy to groups of patients that benefit from the addition of surgery (vs. observation) after chemoradiation.
Financial Disclosure (Caitlin Murphy)
No
FDA Disclosure
Cleared:Yes
Keywords
Esophageal cancer
Neoadjuvant therapy
Clinical practice
Treatment delivery
Abstract ID: 178
Regulation Of E2F1 By A Deubiquitinating Enzyme, UCHL5, For DNA Damage Response.
Author List
1. Presenting Author: Christina Mahanic
2. Additional Author: Varija Budhavarapu
3. Additional Author: Weei-Chin Lin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
E2F1 is a transcription factor that plays a critical role in diverse cellular pathways such as cell cycle progression, apoptosis
induction, and the DNA damage response. E2F1 has been shown necessary for inducing apoptosis in a chemotherapeutic
response by transcriptionally activating target genes such as p73. The mechanism in which E2F1 differentially regulates
transcription of proliferative genes and apoptotic genes remains unknown.
Methods
Our co-IP/MS experiment identifying potential interacting proteins of E2F1 has identified a deubiquitinating enzyme
(DUB), UCHL5. Through further investigation, I have shown that E2F1 interacts with UCHL5 when overexpressed in
293T cells, particularly when the proteasome is inhibited with MG-132.
Results
After 293T cells were treated by a chemotherapeutic drug, adriamycin, the accumulation of E2F1 ubiquitination (K48 and
K63-chain specific) is decreased when UCHL5 is overexpressed, suggesting that UCHL5 is a potential DUB for E2F1. In
addition, a reporter assay has shown that E2F1 transcriptional activity is increased when UCHL5 is present, and QPCR has
shown that an E2F1 target gene, p73, is upregulated when UCHL5 is present. Interestingly, UCHL5 has been shown to
interact with the INO80 chromatin-remodeling complex, placing UCHL5 and the proteasome at the site of transcription. I
hypothesize that UCHL5 is able to interact with E2F1 on the chromatin, and deubiquitinate E2F1 enabling an upregulation
of transcriptional activity of genes required for apoptosis.
Conclusion
I propose that ubiquitination is an additional regulation of transcriptional activity of E2F1. Discovering a mechanism in
which E2F1 transcriptional activity is increased could lead to a possible target therapy in order to induce apoptosis in
cancer cells. In conclusion, I have found that a DUB, UCHL5, interacts with E2F1 and deubiquitinates E2F1 in vivo.
Financial Disclosure (Christina Mahanic)
No
FDA Disclosure
Cleared:Yes
Keywords
E2F1
UCHL5
Deubiquitinating enzyme
DNA damage
Abstract ID: 179
Improving The Efficacy Of Chemotherapy Drugs For The Treatment Of Triple-Negative Breast Cancers
Author List
1. Presenting Author: Behyar Zoghi
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Approximately 15-20% of all breast cancers account for triple negative breast cancers that exhibit aggressive, distinct
metastatic pattern and poor prognosis resulting in disproportionate number of breast cancer death. More than 50% of
patients with triple negative breast cancers develop chemoresistance and do not respond to chemotherapeutic drugs.
Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious
cancer drugs. In spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that
regulate this phenomenon.
Methods
Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant
triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Since
miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that
they represent more attractive targets than the single gene or gene product that is the target of conventional cancer
treatments that are typically prone to drug resistance. Furthermore, since miRNAs are normal constituents of healthy cells,
the introduction of miRNA into healthy cells is not likely to result in severe toxicity as commonly observed in
chemotherapy agents currently being used to treat breast cancers.
Results
 
We have recently demonstrated that miRNAs can be systemically delivered to treat breast cancer lung metastasis without
any hepatotoxicity. In addition to being a potent therapeutic regimen, our preliminary analyses reveal that miRNAs can be
bonafide early prognostic markers to monitor treatment response to specific drugs in triple negative breast cancers.
Conclusion
Taken together, these findings suggest that miRNA can serve as potent therapeutic adjuvants and although the data content
of miRNA profiles is far less than that of gene expression profiles, by virtue of their ability to modulate entire spectrum of
genes and pathways miRNAs have potential to be better classifiers for the prognosis and response to treatment of cancers.
We believe that the identification of miRNAs that mediate chemoresistance could lead to more efficient treatment selection
at the patient level and an improved response rates at the population level.
Financial Disclosure (Behyar Zoghi)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 181
Combination Of TUSC2 Gene Therapy With Targeted Agents For The Treatment Of NSCLC
Author List
1. Presenting Author: Humberto Lara-Guerra
2. Additional Author: Jieru Meng
3. Additional Author: Mourad Majidi
4. Additional Author: Bingliang Fang
5. Additional Author: Lin Ji
6. Additional Author: Jack Roth
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Lung cancer (LC) is the most lethal cancer worldwide with the non-small cell subtype (NSCLC) accounting for 85% of
cases. TUSC2, a novel tumor suppressor gene located on 3p21.3 chromosomal region , is frequently
inactivated in NSCLC. Reexppresion of TUSC2 results in apoptosis through its interaction with Apaf1 and downregulation
of tyrosine kinases including EGFR, PDGFR, c-Kit, and c-Abl in NSCLC but not in normal cell lines. In a phase I clinical
trial for stage IV NSCLC patients progressing following platinum-based regimens, TUSC2 nanoparticles were
delivered safely intravenously. High levels of TUSC2 were detected in tumor samples inducing clinical response. Based on
this evidence we hypothesize that combining targeted therapeutic agents with TUSC2 gene therapy will result
in cooperative growth inhibition and/or cytotoxicity in human NSCLC. Below we have outlined the key goals of the study
and anticipated results.
Methods
A panel of 14 representative NSCLC cell lines harboring clinically relevant mutations (EGFR ex19 del, EGFR L858R,
EGFR T790M, KRAS) will be transfected with TUSC2, Luciferase reporter gene, or empty vector (negative
control) using a lentiviral tet-on inducible expression system. Upon induction, TUSC2 expression will be
assessed for mediating synergism when combined with any of 144 kinase inhibitors. Once synergism is detected, potential
interactions will be confirmed on cell proliferation, cell cycle and apoptotic assays. Pathways responsible for antagonism or
synergism between TUCS2 and relevant targeted agents will be identified using a RPPA platform and mRNA
Affymetrix profiling. Finally, to explore the clinical role of TUCS2 in combination with current clinical practice, the
combination of TUCS2 gene therapy with erlotinib will be explored in phase II clinical trials on EGFR TK wild type
NSCLC patients.
Results
We anticipate that TUCS2 gene therapy will have a synergistic effect with tyrosine kinase inhibitors by
inducing proapoptotic and downregulating target-specific signaling pathways, resulting in cell growth arrest and apoptosis
of NSCLC.
Conclusion
TUCS2 is a novel tumor suppressor gene whose therapeutic implementation may be of high relevance in
overcoming resistance to targeted therapies in NSCLC.
Financial Disclosure (Humberto Lara-Guerra)
No
FDA Disclosure
Cleared:Yes
Keywords
NSCLC
gene therapy
TUSC2
targeted therapy
Abstract ID: 182
QRT-PCR Assay Qualification And Its Application For The Quantitation Of A Therapeutic microRNA (miR-Rx34)
In The Rat And Non-Human Primate
Author List
1. Presenting Author: Kevin Kelnar
2. Additional Author: Heidi Peltier
3. Additional Author: Neil Leatherbury
4. Additional Author: Jay Stoudemire
5. Additional Author: Andreas Bader
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
 
Mirna Therapeutics has developed a therapeutic miRNA, miR-Rx34, a mimic of the miR-34a tumor suppressor miRNA,
for the treatment of cancer. Quantitation of the mimic in biological matrices (whole blood, urine, saliva) requires a
sensitive and selective analytical method. We have developed a qualified assay for RNA isolation and qRT-PCR to
measure the concentration of our miRNA therapeutic in the whole blood of the Sprague Dawley rat and cynomolgus
monkey.
Methods
A robust qualification study design requires the consideration of multiple parameters including RNA yield, accuracy,
specificity, sensitivity, linearity, range, precision (intra- and inter-assay), limits of detection, and limits of quantitation.
Acceptance criteria for each parameter are determined from process samples (pooled whole blood) and then confirmed
using test samples (individual whole blood).
Results
 
Process samples were used to set acceptance criteria of sample preparation and qRT-PCR analysis. RNA isolated from
whole blood of rats and cynomolgus monkeys produced quantifiable yields with high RNA integrity (RIN values above
7.0) and precision (intra- and inter-assay=%CV less than 25%). Utilizing a mimic of miR-34a as the template, the Taqman
miRNA qRT-PCR assay specific for miR-34a produced the following results: 1) linearity; R2â‰¥0.99 and
slope= -3.04Â±0.5, 2) Dynamic Range=1x1010 to 1x104 copies, 3) LLOD=1.4E+03 copies, 4)
LLOQ=4.9E+03 copies, 5) ULOQ=7.0E+09 copies, 6) Accuracy of the range of the assay=%CV less than 25%, 7)
Repeatability (intra-assay)â‰¤0.5Cts, 8) Intermediate Precision (inter-assay)=%CV less than 25%, and 9) Specificity
exhibiting a percent false-positive rate of 0.000%.
Conclusion
 
The qualified procedure was performed on whole blood samples from Sprague Dawley rats and cynomolgus monkeys to
verify the RNA yield, RNA integrity, determine endogenous miR-34a levels, and monitor miR-Rx34 bioavailability over
the time course of the study. The pharmacokinetic and toxicokinetic parameters derived from these studies will be used to
assess the safety of miR-Rx34 as a therapeutic application, as well as to establish human dose levels and regimens.
Financial Disclosure (Kevin Kelnar)
material? Yes
- MIRNA Therapeutics
- MIRNA Therapeutics
FDA Disclosure
Cleared:Yes
Keywords
micrRNA therapeutic
miR-34a
assay qualification
pharmacokinetic
Abstract ID: 183
Small Molecule Inhibition Of The Steroid Receptor Coactivators, SRC-3 And SRC-1
Author List
1. Presenting Author: Ying Wang
2. Additional Author: David Lonard
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Overexpression of steroid receptor coactivator-1 (SRC-1) and steroid receptor coactivator-3 (SRC-3) is associated with
cancer initiation, metastasis, advanced disease and resistance to chemotherapy. In most of these cases, SRC-1 and SRC-3
have been shown to promote tumor cell growth by activating nuclear receptor and multiple growth factor signaling
cascades that lead to uncontrolled tumor cell growth. Up until now, most targeted chemotherapeutic drugs have been
designed largely to block a single pathway at a time, but cancers frequently acquire resistance by switching to alternative
growth factor pathways. We reason that the development of chemotherapeutic agents against SRC coactivators that sit at
the nexus of multiple cell growth signaling networks and transcriptional factors should be particularly effective
therapeutics.
Methods
Using both coactivator activity- and stability-based assays, we sreened a collection of compounds capable of disrupting
nuclear receptor-SRC protein-protein interaction according to pubchem database to identify SRC targeted compounds, a
cadre of compounds that target SRC-3 (and SRC-1) for degradation. we report the discovery of gossypol as a small
molecule inhibitor of coactivator SRC-1 and SRC-3.
Results
Our data indicate that gossypol binds directly to SRC-3 in its receptor interacting domain (RID). In MCF-7 breast cancer
cells, gossypol selectively reduces the cellular protein concentrations of SRC-1 and SRC-3 without generally altering
overall protein expression patterns, SRC-2, or other coactivators such as p300 and CARM1. Gossypol reduces the
concentration of SRC-3 in prostate, lung and liver cancer cell lines. Gossypol inhibits cell viability in the same cancer cell
lines where it promotes SRC-3 downregulation. Additionally, gossypol sensitizes lung and breast cancer cell lines to the
inhibitory effects of other chemotherapeutic agents. Importantly, gossypol is selectively cytotoxic to cancer cells while
normal cell viability is not affected.
Conclusion
This data establishes the proof of principle that, as a class, SRC-1 and SRC-3 coactivators are accessible chemotherapeutic
targets. Given their function as integrators of multiple cell growth signaling systems, SRC-1/SRC-3 SMIs comprise a new
class of drugs that have potential as novel chemotherapeutics able to defeat aspects of acquired cancer cell resistance
mechanisms.
Financial Disclosure (Ying Wang)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 184
Assessing The Impact Of Health Care Shortages On Childhood Cancer Incidence And Mortality In Medically
Underserved Texas Counties
Author List
1. Presenting Author: Elise Brune
2. Additional Author: Karthik Sethuraman
3. Additional Author: Caitlin Keck
4. Additional Author: Chiehwen Hsu
5. Additional Author: Jerry Miller
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cancer is considered to be the most common cause of disease-related mortality in children ages 0 to 19 in Texas. It is
observed that U.S. childhood cancer incidence and mortality may be related to differences in access to health care. Health
service availability in Texas counties is classified under three designations: Medically Underserved Area (MUA),
Medically Underserved Population (MUP), and Exceptional Medically Underserved Population (GOV). It is crucial to
childhood cancer survivorship that proper health resources are available for early diagnosis, quality treatment, and
continued follow-up care. The purpose of this study is to determine whether a relationship exists between childhood cancer
survivorship and underserved status designation in Texas counties.
Methods
This study analyzed incidence, mortality, and population data between 2000 and 2009 for children ages 0 to 19, including
all ethnicities, races, genders, and childhood cancers. Cancer incidence and mortality data were collected through the Texas
Department of State Health Services Texas Cancer Registry and CDC Wonder database. Child population data were
collected from the 2000 U.S. Census. Underserved status designations for 2010 were retrieved from the U.S. Department of
Health and Human Services. Utilizing Spatial Scan Statistic methods, purely spatial analyses were performed using the
discrete Poisson model to identify high risk childhood cancer incidence and mortality clusters. Relationships were assessed
by overlaying underserved status designations with cluster regions using ArcGIS.
Results
Significant incidence and mortality clusters (p<0.05) were identified in South Texas, Gulf Coast, and Dallas/Ft. Worth
Metroplex regions. Within incidence clusters, about three-quarters (72.1%) of counties were Full MUA, one-fifth (19.1%)
Partial MUA, 1.5% Full MUP, 1.5% as Full GOV, and 5.9% as undesignated. Within mortality clusters, more than
two-thirds (69.2%) counties were considered as Full MUA, 24.6% as Partial MUA, 3.1% as Full GOV, and 3.1% as
undesignated. It was observed that a quarter (24.9%) of all MUA counties were included in mortality clusters.
Conclusion
Results from this study reveal that MUA counties were significantly more likely to be located in clusters of higher
childhood cancer incidence and mortality. Underserved status designations of MUP and GOV were inconclusive, most
likely due to their representation of shortages for specific populations not including this age group. A limitation of this
study included suppressed mortality data for protection of confidentiality. It is essential that health disparities, such as
shortages in health services to cancer patients, be addressed in order to decrease the cancer burden in Texas.
Financial Disclosure (Elise Brune)
No
FDA Disclosure
Cleared:Yes
Keywords
Childhood Cancer Incidence
Medically Underserved
Mortality
Health Care Shortages
Abstract ID: 185
The Expression Profile And Target Value Of NR4A1 In Breast Cancer
Author List
1. Additional Author: Jiong Bi
2. Additional Author: Lan Liao
3. Presenting Author: Jianming Xu
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
NR4A1 is a member of the nuclear receptor superfamily and plays an important role in cell growth and apoptosis.
Cytosporone B (Csn-B) is an agonist of NR4A1 and activation of NR4A1 by Csn-B inhibits colon cancer cell growth. This
study is to define NR4A1 expression profiles in mouse and human breast cancers (BCas) and to test whether activation of
NR4A1 can serve as a strategy for BCa therapy.
Methods
The K14cre;p53(f/f);BRCA1(f/f) breast cancer mouse model is used to prepare RNA and tissue sections from early and
late stage mammary tumors. NR4A1 mRNA levels are measured by real time RT-PCR. Mouse and human BCa sections
are used for IHC. NR4A1 protein in BCa cells is measured by Western blot. Cells are treated with Csn-B. Cell growth is
measured by MTS assay.
Results
In mice, NR4A1 mRNA is low in the whole mammary gland (MG) RNA samples and NR4A1 protein is detected in
mammary epithelium by IHC. In the K14cre;p53(f/f);BRCA1(f/f) BCa mouse model, NR4A1 mRNA significantly
increases in the whole tumor RNA samples, which is probably caused by an increase in NR4A1+ cell number because
NR4A1 protein in individual tumor cells is lower than that in normal mammary epithelial cells as detected by IHC. NR4A1
protein is detected in 9 out of 10 early stage and 3 out of 9 late stage tumors from these mice. NR4A1 is detected in the
nuclei of human breast epithelial cells of normal breast tissue, fibrocystic adenosises and fibroadenomas. NR4A1 is also
detected in 50.7% of breast adenocarcinomas (n=142). More specifically, NR4A1 is detected in 60% of DCIS, 52% of
invasive ductal carcinomas and 38.5% of invasive lobular carcinomas. NR4A1 is expressed in 53% and 50% of stage I and
stage II tumors, while only in 30% of stage III tumors. Among 10 BCa cell lines examined, high levels of NR4A1 protein
are found in MCF-7, T47D and Hcc70 cells, while NR4A1 is undetectable in MDA-MB-231 cells. Accordingly, the IC50
value of Csn-B for inhibiting MDA-MB-231 cell growth is 2.2 and 3.4 fold higher than those for inhibiting MCF-7 and
Hcc70 cell growth.
Conclusion
NR4A1 is downregulated during BCa progression, suggesting NR4A1 is a tumor suppressor for breast cancer cell growth
and progression. Therefore, activation of NR4A1 by Csn-B or restoration of NR4A1 expression may inhibit BCa growth
and facilitate breast cancer therapy.
Financial Disclosure (Jianming Xu)
No
FDA Disclosure
Cleared:Yes
Keywords
nuclear receptor
NR4A1
gene expression
breast cancer
Abstract ID: 186
Mesenchymal Stromal Cells To Transfer Inducible Caspase-9 For Lung Cancer Treatment
Author List
1. Presenting Author: Miki Ando
2. Additional Author: Valentina Hoyos
4. Additional Author: Lisa Hayes
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Mesenchymal Stromal Cells (MSCs) are promising agents for the delivery of therapeutic transgenes. MSCs accumulate
selectively at tumor sites because they home to areas of active connective tissue growth. Homing to lung tumors should be
particularly favored since intravenously infused MSCs are entrapped in the lung microvasculature. We hypothesize that
MSCs can be engineered to produce functional adenoviral vectors that will be released at the tumor sites and deliver the
suicide gene product, inducible caspase 9 (iC9). iC9 is activated by a small molecule chemical inducer of dimerization
(CID) to induce apoptosis in transduced tumor cells.
Methods
MSCs derived from six healthy donors were transduced with a replication incompetent adenoviral vector encoding iC9 and
CD19 (as a selectable marker). To enhance adenovector production by these MSCs, they were also nucleofected with a
plasmid encoding the E1A gene product, required for active AdV replication. To confirm E1A-transfected MSCs produced
AdV, the lung cancer cell line A549 was transduced with supernatant from E1A-MSCs transduced with an AdV encoding
GFP. Next, E1A-MSCs and non-E1A MSCs were transduced with Ad-iC9. The supernatant was transferred to H1299
tumor cells and CID was added 48 hours later. For in vivo study, mice were injected with E1A-iC9-MSCs after
establishing an orthotopic lung tumor xenograft. Tumor growth was evaluated by bioluminescence imaging.
Results
After exposure to AdV-iC9-CD19, a mean of 70% MSC expressed CD19, with a peak 48hr to 72hr after transduction.
When CID was added, a mean of 57% of MSC were apoptotic compared to 20% of iC9 transduced cells without CID
treatment, demonstrating that the gene product was functional. We then confirmed that these E1A-MSCs could produce
Adv, initially using a GFP-AdV. Supernatant from E1A-MSC transduced with GFP AdV produced 96% GFP positivity in
A549 cells, versus 33% using control supernatant from E1A negative MSC transduced with the same GFP-AdV. Similarly,
MSC supernatant from E1A-iC9-MSC effectively transduced target H1299 cells, and after addition of CID, 88% apoptosis
was observed, compared to 7.2% apoptosis using iC9 AdV supernatant from MSC lacking E1A. These in vitro results
could be replicated in vivo, where suppression of orthotopic xenografts was observed in the mice receiving E1A-MSCs
followed by CID.
Conclusion
MSCs are transduced efficiently by adenovirus and transfection with E1A allows MSCs to produce adenovirus. To learn
more about the benefits of MSCs expressing Ad- iCas9 treatment in patients with NSCLC, we have begun additional
pre-clinical in vivo efficacy and toxicity testing.
Financial Disclosure (Miki Ando)
No
FDA Disclosure
Cleared:Yes
Keywords
Mesenchymal stromal cell
Caspase9
adenovirus
lung cancer
Abstract ID: 187
Analysis Of Cardiac Function In A Pediatric Mouse Model Of Doxorubicin-induced Cardiotoxicity Using
Echocardiographic Strain Imaging
Author List
1. Additional Author: Thomas Andrews
2. Additional Author: Merry Lindsey
3. Presenting Author: Gregory Aune
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Long-term survivors of pediatric cancer that were exposed to anthracyclines have a significantly increased lifelong risk of
cardiomyopathy and congestive heart failure. The cellular and molecular mechanisms by which acute anthracycline
exposure damages the pediatric myocardium and leads to cardiomyopathy decades later are incompletely understood.
Because the number of long-term survivors is increasing, and this population is aging, there is a critical need to develop
laboratory models to dissect the cellular and molecular mechanisms of anthracycline-induced myocardial injury. Here, we
report the feasibility and reproducibility of using echocardiographic longitudinal strain imaging in a pediatric mouse model
of anthracycline-induced cardiotoxicity.
Methods
C57/BL6J mice (2 weeks old) were injected intraperitoneally with saline as a control or three different doses of
doxorubicin (1 mg/kg, 3 mg/kg, and 5 mg/kg) weekly for a total of three weeks. Serial echocardiographic analysis using
the VisualSonics Vevo 2100 ultrasound was performed under sedation at 3 and 5 weeks of age. For each animal,
longitudinal strain, ejection fraction, and fractional shortening was quantified using the VisualSonics VevoStrain software
according to the manufacturerâ€™s recommendations.
Results
Echocardiographic analysis of longitudinal strain in pediatric mice at 3 and 5 weeks of age is both feasible and
reproducible. When compared to saline control, doxorubicin exposure at all three doses resulted in significant reductions in
peak systolic longitudinal strain (-26 +/- 6% for control injected animals versus -15 +/- 4% for doxorubicin treated
animals) Similar reductions in ejection fraction and fractional shortening were also noted in doxorubicin-treated mice.
Somewhat surprisingly, there was no statistically significant difference in peak systolic strain, ejection fraction, or
fractional shortening between the three different doses of doxorubicin, indicating that even a very low dose of doxorubicin
induced cardiac dysfunction.
Conclusion
Pediatric mice tolerate intraperitoneal injection with doxorubicin and serial echocardiography requiring sedation. Ongoing
studies are focused on utilizing echocardiographic longitudinal strain to quantify cardiotoxicity during five weeks of acute
anthracycline exposure followed by 13 weeks of recovery after discontinuation of therapy. Together, the phases of
treatment and recovery are analogous to pediatric cancer therapy followed by decades of recovery from antecedent
myocardial injury.
Financial Disclosure (Gregory Aune)
No
FDA Disclosure
Cleared:Yes
Keywords
Cardiotoxicity
Anthracyclines
Echocardiography
Longitudinal strain
Abstract ID: 188
Development Of Cancer Traps For Eliminating Metastatic Melanoma Cells
Author List
1. Additional Author: Cheng-Yu Ko
2. Additional Author: Lanxiao Wu
3. Additional Author: Ashwin Nair
4. Additional Author: Yi-Ting Tsai
5. Additional Author: Victor K. Lin
6. Presenting Author: Liping Tang
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Our recent studies have shown that biomaterial implants recruit inflammatory cells, stem cells and even cancer cells.
Inflammatory responses, specifically cytokines and chemokines, mediate cancer cell metastasis and recruitment. While
recent studies have shown that, possibly cancer cells migrate from peritonea to lymphatic system via CCR7/CCL21
pathway and then to implantation sites via CXCR4/SDF-1Î± pathway, our studies have found that CXCR4 inhibition but
not CCL21 blocking affects implant mediated melanoma cancer cell recruitment, indicating a more dominant role for
CXCR4/SDF-1Î± . In this light, we have recently developed a novel tissue scaffold that preserves the bioactivity and
delivers cytokines/ chemokines over time. Using melanoma as a model cancer and based on our earlier findings, we first
tested specific chemokines capable of recruiting circulating melanoma cells and then hypothesized that incorporating such
chemokines in our novel scaffolds can recruit and possibly trap the circulating melanoma cells.
Methods
To test our hypothesis of using chemokine loaded scaffolds as cancer traps, protein microbubble-PLGA scaffolds were
loaded with various chemokines like SDF-1Î± and also erythropoietin (EPO), whose receptors are known to be
over-expressed in malignant melanoma cells. 24 hours following NIR labeled B16F10 melanoma cell injection, animals
were imaged under Kodak FX Pro in vivo imaging system and survival of animals recorded. Statistical analyses were
carried out using Student t- test.
Results
As anticipated, scaffold implants prompted the recruitment of cancer cells to the implantation sites. Interestingly,
SDF-1Î±-releasing scaffold implant did not exert a significant influence on cancer cell migration as compared to the
control. On the other hand, EPO-releasing scaffolds prompted more melanoma cell migration than both SDF-1Î± and
control scaffolds. Although not very clear, it is possible that localized release of EPO by scaffolds may alter melanoma
cancer cell responses accounting for different cancer cell responses. In fact, animals with EPO scaffolds had >30% survival
as compared to others.
Conclusion
Our findings suggest that tissue engineering scaffolds can be used as a melanoma cancer cell recruiting device and in future
such recruited cancer cells can be locally annihilated thereby improving life expectancy of cancer patients. The results from
this work will help apply tissue engineering tools like scaffolds for treatment of various other cancers and greatly improve
the quality of life of cancer patients.
Financial Disclosure (Liping Tang)
No
FDA Disclosure
Cleared:Yes
Keywords
Tissue scaffold
metastatic
sustain release
melanoma
Abstract ID: 189
Promotoras And EPICO: Education To Promote Improved Cancer Outcomes
Author List
1. Presenting Author: Julie StJohn
2. Additional Author: Chris Beaudoin
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Ã‰PICO: Education to Promote Improved Cancer Outcomes is a tailored training program on prevention, treatment and
healthy survivorship for colorectal, breast, and cervical cancers among at-risk residents living in South Texas along the
U.S.-Mexico border through training and utilizing promotores to deliver tailored education that improves access to
comprehensive cancer services. The specific aims Ã‰PICO include: 1) equip promotores to educate residents on
prevention, treatment, and survivorship issues related to colorectal, breast, and cervical cancers; 2) enable promotores to
use tailoring strategies to improve their outreach efforts; and 3) increase residentsâ€™ prevention, treatment, and healthy
survivorship behaviors.
Methods
 
Project methods include: 1) EPICO promotores enrolled and completed a CHW instructor certification and training
program; 2) EPICO promotores were trained in focus group moderation; 3) EPICO promotores conducted focus groups to
inform training module development; 4) EPICO promotores received certified CEU training on tailored messaging; 5)
EPICO team of promotores, researchers, and field experts developed bilingual training modules covering prevention/early
detection; treatment options; and survivorship issues for breast, cervical, and colorectal cancers; 6) pilot tested trainings
and revised curriculum; 7) conducted training sessions with outside agency promotores and conducted pre and post tests
and training evaluations; and 8) promotores implemented tailoring-based training in their outreach activities and
administered evaluation tools.
Results
 
As part of the project outcomes, 6 EPICO promotores became DSHS certified Promotora Instructors and had a key role in
developing and delivering cancer education training modules. The project has 20 approved DSHS CHW CEU modules
covering topics such as cancer prevention and early detection, treatment, and survivorship for breast, cervical, and
colorectal cancers; cancer during pregnancy; and fertility and pregnancy options for cancer survivors. To date, 94
promotores attended the breast cancer trainings, receiving a total of 734 DSHS certified CEUs. For cervical cancer, 75
promotores attended, providing a total of 600 DSHS certified CEUs. An estimated 80 promotores will receive 640 CEUs
on colorectal cancer in August 2012. In addition, over 100 promotores received training and certified CEUs on cancer
prevention/early detection, treatment, and survivorship for pregnant residents and fertility and pregnancy options for cancer
survivors. Promotores are currently educating residents through daily outreach activities and have reached approximately
500 residents.
Conclusion
Ã‰PICO provides effective, culturally relevant, sustainable, tailored strategies for addressing cancer prevention,
treatment, and survivorship. The identification of low-cost cancer prevention and education interventions that can impact
entire populations will also add to the knowledge base and inform strategies designed to facilitate positive cancer
outcomes.
Financial Disclosure (Julie StJohn)
No
FDA Disclosure
Cleared:Yes
Keywords
Promotoras
Training
Tailored Messages
Hispanics
Abstract ID: 190
DksA Regulates Genome-wide Transcript Elongation And Opposes Amino Acid Starvation-induced Transcription
Stalling
Author List
1. Presenting Author: Yan Zhang
2. Additional Author: Jeff Grass
3. Additional Author: Rachel Mooney
4. Additional Author: Robert Landick
5. Additional Author: Jue Wang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Genomic instability is a characteristic feature of cancer. To maintain genomic stability, cells must ensure completion and
accuracy of DNA replication, a demanding process facing interference from both exogenous and intrinsic factors. In
Escherichia coli, the transcription factor DksA protects DNA replication from interference by transcription
elongation complexes upon amino acid starvation. However, the extent to which DksA directly affects RNA chain
elongation by RNA polymerase in vivo is unknown.
Methods
To understand how DksA regulates transcription elongation to prevent the replication-transcription conflict, we applied
ChIP-chip (Chromatin Immuno-Precipitation with Microarray) method to analyze the association of RNA polymerase
(RNAP) to the E. coli chromosome.
Results
Here we document genome-wide interactions of DksA with RNA polymerase throughout transcription units. Deletion of
DksA decreases RNA polymerase progress through genes, supporting an in vivo role of DksA in preventing
transcription stalling. Polymerase stalling is exacerbated when translation is slowed by charged tRNASer
depletion and consequent uncoupling of transcription and translation. DksA minimizes the extent of polymerase stalling
and its deleterious effect on replication.
Conclusion
Our results establish a new function of DksA in aiding transcript elongation and ameliorating the consequences of
transcription-translation uncoupling, and strongly suggest that nutritional changes can be transmitted via the mutual
interaction of translation, transcription and replication to impact cell viability.
Financial Disclosure (Yan Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 191
Ecologic Analysis Of Water Contaminants And Leukemia And Lung Cancer Incidence In Texas
Author List
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Available literature suggests that water contaminants act as carcinogens. Four prevalent chemicals, nitrate, nitrite, arsenic,
and fluoride, were chosen for analysis. While these substances have been identified as potential carcinogens in laboratory
settings, findings on their effects as water contaminants are conflicting. The present ecologic study examines whether the
chosen water contaminants are associated with elevated levels of leukemia or lung cancer.
Methods
Water contaminant data was obtained from the United States Geographical Survey. Water was sampled from ground and
surface water sources across Texas and was subsequently filtered and tested for chemical levels. Each chosen chemical was
recorded at least 2000 times between 01/01/2000 and 12/31/2009. Annual cancer incidence data between 2000 and 2009
was obtained at the county level from the Texas Cancer Registry. Two different analyses are proposed: first, discrete
cluster analysis employing the space-time scan statistic to determine and compare spatiotemporal clusters of leukemia and
lung cancer (controlling for race/ethnicity, sex, and age) and spatiotemporal clusters of water contamination; second,
multiple regression analysis to correlate levels of the four contaminants and relative risks of leukemia and lung cancer
(calculated through Poisson regression).
Results
None of the contaminant levels are significantly correlated with leukemia relative risk. Additionally, there is no significant
spatiotemporal overlap between contaminant and leukemia clusters (defined as having at least half of cluster counties
shared across contaminant and cancer clusters). However, nitrate, nitrite, and arsenic levels are significant correlated with
lung cancer relative risk. Nitrate levels have Spearmanâ€™s Ï• 0.450, nitrite levels have Spearmanâ€™s Ï• 0.325, and
arsenic levels have Spearmanâ€™s Ï• 0.244 (all p<0.001). Furthermore, nitrate and nitrite clusters have significant
spatiotemporal overlap with lung cancer clusters.
Conclusion
Increased presence of nitrate and nitrite in water appears to cause definitive increase in lung cancer in terms of regression
correlation and spatiotemporal overlap. Increased presence of arsenic appears to cause increase in lung cancer in terms of
regression correlation but is inconclusive in terms of spatiotemporal overlap. Fluoride in water does not demonstrably
affect lung cancer, and none of the contaminants demonstrably affect leukemia. This studyâ€™s main limitation is lack of
individual-level causation. While this study has great scope through statewide and decade-long water data, it lacks
individual-level cancer data. Thus, all findings require validation by individual-level prospective studies. Nevertheless,
significant correlations and spatiotemporal overlaps strongly argue for further investigation of the effects of nitrate, nitrite,
and arsenic in water on lung cancer.
No
FDA Disclosure
Cleared:Yes
Keywords
Cluster Analysis
Multiple Regression Analysis
Water Contaminants
Spatiotemporal Clusters
Abstract ID: 192
Geographic Variation Of The Impact Of BTEX Compounds On Rates Of Leukemia In Texas Between 2000 And
2009
Author List
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The removal and distribution of waste has disseminated waste locations throughout Texas. BTEX compounds (benzene,
toluene, ethylbenzene, and xylenes) are volatile organic compounds found in petroleum derivatives which end up in storage
tanks that contain gasoline or other petroleum-related products. Literature states that BTEX compounds are known for
having harmful effects on the central nervous system and suggests that BTEX compounds may have carcinogenic effects
by increasing the probability of cancers such as leukemia and lung cancer. In order to explore this further, Texas
countiesâ€™ rates of leukemia and lung cancer were compared to their levels of BTEX Compounds.
Methods
This study viewed cancer, population, and pollutants data between 2000 and 2009. We collected cancer data from the
Texas Cancer Registry site and BTEX compounds release data from the United States Environmental Protection Agency
site at the county level. A cluster analysis found spatiotemporal clusters of locations with pollutants that contain significant
amounts of BTEX compounds and counties containing heightened amounts of leukemia and lung cancer. We used
ARCGIS to map these rates by locations. Trends and patterns of distribution were examined as indicators of potential
relationships. Graphs were plotted and regression analysis was performed in Excel to find correlation between BTEX
compounds locations and lung cancer or leukemia.
Results
Our analysis identified Texas counties containing significant amounts of BTEX compounds and those with high leukemia
and lung cancer rates. Counties along the southeast border of Texas had significant amounts of both BTEX Compounds
and leukemia rates. Linear regressions did not indicate any relationship between BTEX Compounds and the cancers.
However, when nonlinear relationships were examined, while no relationship was found between BTEX Compounds and
lung cancer rates with a Spearmanâ€™s Ï• of 0.23, a nonlinear relationship was found between BTEX Compounds and
leukemia rates, with a Spearmanâ€™s Ï• of 0.73.
Conclusion
While results had no indication of a linear relationship, a nonlinear relationship was found evident between BTEX
Compound values and leukemia rates. This study had limitations such as differing ethnicity and age concentrations across
counties, for which we were not able to account in our analysis in addition to failure to report rates of release by waste
locations. Significant correlations which were found indicate further analysis should be performed to better evaluate the
relationship between BTEX compounds and carcinogens as it could drastically decrease the rates of mortality and
incidence of lung cancer and leukemia in Texas.
No
FDA Disclosure
Cleared:Yes
Keywords
Cluster Analysis
Multiple Regression Analysis
BTEX Compounds
Spatiotemporal Clusters
Abstract ID: 193
16-Channel Receive Array for Proton Imaging and Spectroscopy at 7T
Author List
1. Presenting Author: Samantha By
2. Additional Author: Joseph Rispoli
3. Additional Author: Jiaming Cui
4. Additional Author: Sergey Cheshkov
5. Additional Author: Ivan Dimitrov
6. Additional Author: Craig Malloy
7. Additional Author: Steven Wright
8. Additional Author: Mary McDougall
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The enhanced signal-to-noise ratio of high field MRI at 7T promises improved quantification of various metabolites useful
for diagnosis and monitoring of breast cancer. This abstract reports a 16 channel receive array coil that can be inserted into
a quadrature breast transmit coil to enable localized 1H spectroscopy with far greater sensitivity than using the transmit coil
in transmit/receive mode. Additionally, a unique decoupling method which prevents interaction between the existing 1H
transmit coil and the 16 channel receive coil is described.
Methods
The 16 channel receive array was designed using a soccer ball element geometry, utilizing pentagon and hexagon tiles to
effectively pack corresponding smaller (I.D. 58.5 mm) and larger diameter (I.D. 70 mm) coil elements onto the shell. Coil
overlap is implemented to minimize mutual reactance between nearest neighbors. Decoupling between non-nearest
neighbors was provided through the use of isolating preamplifiers in the 16-channel receiver box. Isolation of the transmit
and receive elements is critical, as coupling will significantly degrade the localization properties of the array as well as lead
to potential patient heating. During transmit, passive and active traps are used to prevent currents from being induced in the
receive elements. The same technique is commonly used in the transmit elements during receive. However, the forced
current excitation design of the transmit coil enabled a much simpler approach. In the FCE approach, two elements are
connected at a common voltage point, where activating a single PIN diode trap circuit open-circuits the transmit array
elements. This approach will help prevent degradation of the linewidth due to direct currents present near the sample
during receive.
Results
Initial testing on the Philips 7T scanner at UTSW indicated sufficient isolation of non-nearest neighboring receive elements
by the preamp decoupling. The FCE decoupling method was compared to a commercial transmit/receive head coil (Nova
Medical, Wilmington, MA) with a single element of the 16 channel array, with no measureable difference. Signal-to-noise
measurements on the 7T scanner indicated as much as a factor of four improvement directly in front of the array element.
Conclusion
Single element testing at 7T demonstrates the functionality of individual coil elements with the associated hardware. Based
on initial results, we expect to see a significant increase in signal-to-nose ratio over a transmit/receive volume coil as a
result of the additional localization of the array elements. Patient imaging will follow thermal safety testing and approval
by the investigational review board.
Financial Disclosure (Samantha By)
No
FDA Disclosure
Cleared:Yes
Keywords
proton imaging and spectroscopy
breast cancer
high-field MRI
16-channel array
Abstract ID: 194
Identifying Substrates For Sialyltransferases In Cancer Cell Lines Using Chemical Labeling Methods
Author List
1. Presenting Author: Yibing Wang
2. Additional Author: Jennifer Kohler
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Glycosyltransferases are enzymes responsible for glycosylation of proteins in cells and among them, sialyltransferases are
a subset of glycosyltransferases which add sialic acid to the non-reducing end of glycans of glycoproteins and gangliosides.
Over the past decades, sialyltransferases have been found to play key roles in the metastasis of malignant carcinomas. On
the other hand, the exact mechanism and function have been poorly understood since little information has been known of
the substrates for sialyltransferases. Identification of the substrates for sialyltransferases implicated in tumors is pivotal in
understanding cancer metastasis and meanwhile is relatively challenging due to lack of reliable approaches. 
We have utilized chemical method to selectively label the sialic acid-containing glycoproteins on cell surface
overexpressing sialyltransferases which we are interested in and have visualized them by immunoblotting. Then we
submitted the protein hits for MS analysis and identified the proteins which were potential substrates for sialyltransferases.
Methods
We established SW48 (colorectal carcinoma), MDA-MB-231 (breast cancer), SKOV3 (ovarian cancer) cell overexpressing
sialyltransferases by infecting the parental cell lines with lentiviruses. The overexpression of these sialyltransferases in
these cell lines was validated. Then we treated the cells with sodium periodate to selectively generate aldehyde group of
sialic acid on cell surface. We conjugated the oxidized sialic acid with biotin aminooxy and therefore labeled the sialic
acid-containing glycans on cell membrane. 
We observed sialylation of some proteins in cells overexpressing sialyltransferases were elevated as compared with their
parental cell lines by immunoblotting, suggesting that they were putative substrates for sialyttransferases. We then purified
the sialylated proteins by streptavidin beads and stained the proteins by silver staining. Then we identified the proteins by
SILAC quantitative MS analysis.
Results
We identified some protein hits which were highly likely substrates for sialyltransferases by chemical labeling methods.
Conclusion
Then we plan to validate the hits by well-established biochemical assays and eventually decipher their roles in cancer
metastasis in future.
Financial Disclosure (Yibing Wang)
No
FDA Disclosure
Cleared:Yes
Keywords
sialyltransferase
metastasis
MS analysis
Chemical labeling
Abstract ID: 195
Changes In Adjuvant Breast Cancer Chemotherapy Regimen Selection Over Time In The Community
Author List
1. Presenting Author: Debra Patt
2. Additional Author: Janet Espirito
3. Additional Author: Brian Turnwald
4. Additional Author: J. Russell Hoverman
5. Additional Author: Marcus Neubauer
6. Additional Author: Thomas Cartwright
7. Additional Author: Leslie Busby
8. Additional Author: Barry Brooks
9. Additional Author: Mark Sitarik
10. Additional Author: michael Kolodziej
11. Additional Author: Roy Beveridge
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Adjuvant breast cancer (BC) chemotherapy (CT) treatment has evolved over time due to improved understanding of risk
conveyed by pathology and patient (pt) characteristics, as well as emergence of new and mature data for survival and
toxicity. We aimed to evaluate how CT regimen selection has changed in recent years in various subgroups.
Methods
Using iKnowMedTM EHR data from The US Oncology Network, we retrospectively identified female pts diagnosed with
stage I-III BC between 1/2007 and 12/2010 at practices with EHR data available at time of diagnosis. Pts with <5 office
visits, those with a second primary or previous cancer diagnoses were excluded. Age, ER, HER2, nodal status, stage and
year of diagnosis were captured. CT utilization was determined by the number of pts who received CT within 6 months
of their diagnosis. Clinical trial pts were included. Regimens were categorized by the initial CT title and drugs assigned.
Pts with metastatic regimens were excluded . CT regimens were analyzed by subgroups and trended over time.
Results
During the time period, 26,095 stage I-III BC pts were identified. A CT regimen within 6 months of diagnosis was
documented in 56% of pts. CT utilization was 83% in HER2+ pts, 85% in ER-/HER2- pts, and 45% in ER+/HER2- pts.
CT utilization decreased overall with increasing pt age (71%, 64%, 51%, 33%, and 13% for pts in their 4th, 5th, 6th, 7th
and â‰¥8th decade of life). In HER2+ pts, use of non-anthracycline containing regimens increased from 26 to 62%, and
anthracyline-taxane combination regimens decreased from 33 to 15%. In HER2-/ER+ pts, the most used non-anthracycline
regimen was docetaxel + cyclophosphamide (TC) at 41%. Anthracycline-taxane combinations were used more often in the
HER2-/ER- group (32%).
Conclusion
In the 4 year study period, this data suggests that ER and HER2 status may drive chemotherapy choice more than nodal
status. Anthracycline containing regimens are being used less often possibly due to similar efficacy but less cardiac
toxicity, particularly when combined with trastuzumab. These results suggest a change away from anthracyclines in
specific subgroups with the controversy over the benefits of that change unsettled, and cost implications yet unquantitated.
Financial Disclosure (Debra Patt)
No
FDA Disclosure
Cleared:Yes
Keywords
Outcomes Research
Breast Cancer
Chemotherapy
Health Services Research
Abstract ID: 196
Primary And Secondary Pegfilgrastim Utilization In Adjuvant Chemotherapy For Breast Cancer In The
Community
Author List
1. Presenting Author: Debra Patt
2. Additional Author: Janet Espirito
3. Additional Author: Brian Turnwald
4. Additional Author: J. Russell Hoverman
5. Additional Author: Marcus Neubauer
6. Additional Author: Leslie Busby
7. Additional Author: Barry Brooks
8. Additional Author: michael Kolodziej
9. Additional Author: Roger Anderson
10. Additional Author: Roy Beveridge
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Various factors are taken into consideration in the selection of adjuvant breast cancer (BC) chemotherapy (CT) regimens
for patients. Choice of CT, schedule, duration, and supportive care affects costs and toxicity. Understanding clinical
practice utilization patterns are important when making cost estimates of adjuvant therapy. Because pegfilgrastim is a
large driver of cost it is important to understand the utilization characteristics. We aimed to characterize primary and
secondary pegfilgrastim use during neoadjuvant/adjuvant (N/Ad) chemotherapy by regimen type.
Methods
Using the US Oncology iKnowMed EHR database, we retrospectively identified female BC patients (pts) diagnosed with
stage I-III BC, between 7/2006 and 11/2010. Secondary diagnoses were excluded. Pts were characterized by age, ER and
HER2 status, tumor size, grade, and nodes. CT utilization was determined by the number of pts assigned an N/Ad line of
therapy (LOT) during the study period.
Results
General chemotherapy and pegfilgrastim utilization characteristics were previously reported. This report captures primary
vs. secondary pegfilgrastim use. During the time period, 40,881 BC pts were identified. Of these, 15,328 pts (37%) were
assigned an N/Ad CT regimen and 72% (11, 022 pts) received pegfilgrastim at any time within 6 months of their N/Ad
regimen. Docetaxel containing regimens (TC, TAC, TCH) and dose-dense regimens accounted for the majority of all
pegfilgrastim use. Pegfilgrastim utilization with the TC regimen was 70%, and represented 25% of all N/Ad pegfilgrastim
utilization. The vast majority of utilization for TC and TCH was primary prophylaxis.
Conclusion
While primary prophylaxis in regimens like dose-dense AC and TAC are expected, the primary utilization of pegfilgrastim
in TC and TCH is higher than expected based on published clinical trial experience. The incidence of FN has been
reported at 5% in the clinical trial by Jones et al with TC, however subsequent reports suggest the incidence of FN may be
higher than expected. Our results demonstrate high primary prophylaxis utilization adoption in clinical practice. With
the availability of generic docetaxel, commonly used drugs in adjuvant BC except trastuzumab have generic equivalents.
Pegfilgrastim will be the largest cost driver in women receiving adjuvant chemotherapy and should be considered among
cost estimates. This study may underestimate utilization of pegfilgrastim if it was administered outside of the
Financial Disclosure (Debra Patt)
No
FDA Disclosure
Cleared:Yes
Keywords
breast cancer
outcomes research
health services research
pegfilgrastim
Abstract ID: 197
High Burden Of Late Effects Upon Entry Into Head & Neck Cancer Survivorship Care
Author List
1. Presenting Author: Katherine Hutcheson
2. Additional Author: Charles Schreiner IV
3. Additional Author: Fran Zandstra
4. Additional Author: Ludivine Russell
5. Additional Author: Mark Zafereo
6. Additional Author: Carol Lewis
7. Additional Author: L. Kay Bartholomew
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Almost 15,000 Texans are survivors of head and neck cancer (HNC) diagnosed since 1995 (Texas Cancer Registry). HNC
survivors suffer distinct late effects because of the adverse impact of tumor and treatment on upper aerodigestive tract
(UADT) function. In the current paradigm, survivorship care starts years after cancer therapy upon transition into formal
survivorship or posttreatment surveillance programs. Most late effects are irreversible at this point. Our objective was to
evaluate the burden of late effects upon entry into a formal HNC survivorship program.
Methods
The HNC Survivorship Clinic (HNSVC) at the University of Texas MD Anderson Cancer Center (Houston, TX) provides
site-specific survivorship care to disease-free survivors a minimum of 30 months after cancer therapy. Individualized care
plans (â€œPassportsâ€•) are completed by HNSVC clinicians per recommendations of the Institute of Medicine. Passports
include documentation of 14 late effects. We conducted a retrospective analysis of HNC survivors with UADT primary
tumors who transitioned care into the HNSVC 06/2010â€“07/2011. Skin, thyroid, and salivary tumors were excluded. The
Survivorship database was queried and cross-referenced with the electronic medical record. Prevalence and patterns of late
effects were explored upon transition into the HNSVC.
Results
Ninety-seven HNC survivors transitioned care into the HNSVC in the initial year of the program. The median age was 64
(range: 43-88); 75% were male. Primary tumors included oropharyngeal (45%), oral cavity (32%),
laryngeal/hypopharyngeal (14%), unknown primary (5%), and nasopharyngeal (3%). Forty-seven percent (45/97) of
survivors had been treated with surgery (15 primary site, 18 neck, 12 primary + neck), and 90% (87/97) received
radiotherapy (69 definitive, 18 postoperative). Sixty-seven percent had clinician-reported late effects upon transition into
survivorship care. The most common late effects were oral complications (40%; e.g. xerostomia, radionecrosis) and
dysphagia (22%). Prevalence of late effects was highest in patients who received radiotherapy (p=0.001).
Conclusion
More than half of HNC survivors have clinically detectable late effects when they transition care into a formal survivorship
program. The most common late effects in this study were oral complications and dysphagia. While typically irreversible
by the time of transition into survivorship care, data suggest that these problems can be lessened by early adoption of
disease-specific health behaviors such as dental prophylaxis and targeted exercise. Thus, interventions targeting late effects
in HNC should consider a proactive model before or during cancer therapy rather than a reactive approach of waiting to
address late effects after transition into formal survivorship programs.
Financial Disclosure (Katherine Hutcheson)
No
FDA Disclosure
Cleared:Yes
Keywords
Survivorship
Late effects
Head and neck cancer
Toxicity
Abstract ID: 198
Guiding Percutaneous Lung Intervention With Dynamic Image Estimation
Author List
1. Additional Author: Tian Cheng He
2. Additional Author: Kongkuo Lu
3. Additional Author: Po Su
4. Presenting Author: Zhong Xue
5. Additional Author: Kelvin Wong
6. Additional Author: Miguel Valdivia Y Alvarado
7. Additional Author: Stephen Wong
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
systempicture.jpg
Summary
Introduction
Percutaneous lung intervention is a traditional procedure for biopsy, ablation, and local treatments of lung cancer. Due to
the lack of real-time imaging, targeting small peripheral lung tumors still remains challenging. In this work, we propose a
dynamic image guidance system, in which a motion compensation approach is integrated to estimates 3D CT images
driven by real-time tracked chest surface motion.
Methods
The interventional needle is tracked by using an electromagnetic (EM) device. By calibrating the transformation between
the EM and CT coordinates, tracked needle can be visualized in CT for guiding percutaneous lung intervention. Since the
static CT does not reflect the patientâ€™s dynamic anatomy especially respiratory motion, dynamic CT images are
estimated by using the real-time tracked chest surface sensors. We previously trained a joint Principal Component Analysis
(PCA) model to characterize the relationship between longitudinal 3D CT deformation and chest surface signals, by using
the 4D CT data collected retrospectively, in the template space. Then, during intervention, this statistical model is utilized
to estimate a patient-wise respiratory pattern from the real-time chest surface sensor signals, so as to generate a series of
CT images that cover the phases of entire respiratory cycle of a patient whose 4D CT is not available. The estimated CT
images are updated dynamically corresponding to the latest respiratory status to provide a road-map for interventional
device visualization and procedure guidance.
Results
4D CT data from thirty patients were used to evaluate our method using leave-one-out strategy. Each time 29 subjects were
used to train the PCA model, and the left out subject was used for testing. The differences between the estimated serial CTs
and the real 4D CTs were calculated as the accuracy of the proposed algorithm. The results showed that average lung field
surface distance across all the 30 experiments was 2mm. Three volunteer data were used to test the guidance work-flow
without needle puncture. Preliminary results showed feasibility of the dynamic image guidance procedure.
Conclusion
Different from the traditional CT-guided procedure, which utilizes a static 3D CT image as the road-map, a motion
compensation method is used in our new system to estimate the dynamic anatomical images of patients from the
pre-procedural CT and real-time tracked sensor signals. Simulation results showed accurate estimation of the lung field
motion, and feasibility of the work-flow was tested with volunteers. The proposed system has potentials to reduce frequent
intra-procedural scanning and improve procedure performance. 
Financial Disclosure (Zhong Xue)
No
FDA Disclosure
Cleared:Yes
Keywords
image-guided intervention system
electromagnetic tracking
lung cancer
respiratory motion compensation
Abstract ID: 199
Inhibition Of Breast Cancer Stem Cells By Endostatin-Cytosine Deaminase-Uracil Phosphoribosyltransferase
Author List
1. Presenting Author: Wen-Hsuan Yu
2. Additional Author: Chun-Te Chen
3. Additional Author: Mien-Chie Hung
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Therapeutic strategies targeting angiogenesis by blocking vascular endothelial growth factor/receptor (VEGF/VEGFR)
have been clinically used for treating various cancers. However, recent reports have shown that VEGF inhibitors reduce
primary tumor growth but promote tumor invasiveness and metastasis, which may result from an increased cancer stem
cells (CSCs, or tumor initiating cells, TICs) population by VEGF inhibition. Furthermore, it has been reported that
glioblastoma stem-like cells give rise to endothelium and contribute to tumor neo-angiogenesis. With increasing evidence
showing that CSCs account for cancer initiation, progression and chemotherapeutic resistance. Breast cancer stem cells
(BCSCs) or breast cancer initiating cells (BCICs) were identified as an enriched CD44+/CD24subpopulation of cancer cells. It has been reported that the Integrin-FAK signaling axis play a role in maintaining
the mammary cancer stem/progenitor cell populations and promoting breast cancer development and progression. Thus, the
development of therapeutic drugs that target the BCSCs through inhibition of the Integrin-FAK axis may potentially
eliminate cancer initiation and progression. We have previously developed a fusion protein, Endo-CD (endostatin-cytosine
deaminase-uracil phosphoribosyltransferase), which has dual function. Endostatin (Endo) is a â€œcytostaticâ€• agent,
which acquires its tumor targeting ability by recognizing integrin receptors, as well as a cell surface receptor of tumor
endothelial cells and tumor cells. Cytosine deaminase (CD) is a â€œcytotoxicâ€• protein, which can convert the non-toxic
pro-drug 5-fluorocytosine (5-FC) into the chemotherapeutic drug 5-fluorouracil (5-FU). Endo-CD selectively targets
integrin-expressing tumor cells and mediates tumor killing effect. Interestingly, we found that breast cancer stem cells
(BCSCs) exhibit higher integrin expression. Therefore, we asked if Endo-CD could selectively target and suppress
integrin-enriched BCSCs population.
Methods
We investigate the individual treatments of Endo, CD/5-FC or EndoCD/5-FC for their activities toward eliminating BCSCs
in different breast cancer cell lines such as MDA-MB-231 and BT549 in vitro and orthotopic xenograft breast
cancer mice model in vivo. To detect the BCSC population, we use different BCSC markers such as
CD44+/CD24- and also mammospheres formation assay for further validation.
Results
Our data showed that Endo-CD/5FC treatment selectively reduced CD44+/CD24- BCSCs
population in a dose dependent manner and reduced mammosphere formation in vitro and in vivo.
Also, Western blot data shows that FAK kinase activity is downregulated after EndoCD/5-FC treatment.
Conclusion
In summary, Endo-CD/5-FC may eliminate BCSCs by targeting integrins and inhibiting its downstream signaling, which
could synergize with 5-FU cytotoxicity and effectively block tumor angiogenesis and tumor progression.
Financial Disclosure (Wen-Hsuan Yu)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast cancer
Cancer stem cell
target therapy
angiogenesis
Abstract ID: 200
A Novel Regulatory Role Of APE1/acetylated APE1 In Lung Cancer Cell Proliferation
Author List
1. Presenting Author: Shiladitya Sengupta
2. Additional Author: Kishor K Bhakat
3. Additional Author: Larry J Bellot
4. Additional Author: Victor A Adeniyi
5. Additional Author: Steven Widen
6. Additional Author: Mala Sinha
7. Additional Author: Bruce A Luxon
8. Additional Author: Sankar Mitra
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Mammalian AP-endonuclease (APE1/Ref-1), a key DNA base excision repair protein has an important function in
transcriptional regulation. It is overexpressed in nearly all tumor tissues of diverse origin and is invariably associated with
their chemo-drug resistance. APE1 is post-translationally acetylated at Lys 6 and 7. Our initial observation showed
predominant presence of acetylated APE1 (AcAPE1) in different tumor tissues as compared to their adjacent normal
counterparts and its essentiality for cell proliferation. We hypothesize that AcAPE1 is critically involved in tumor
cell-specific functions which are phenotypically manifested as sustained proliferation, drug resistance etc.
Methods
We carried out Affymetrix Gene-Chip expression analysis in lung-adenocarcinoma A549 and normal bronchial-epithelial
BEAS-2B lines by modulating APE1 levels. Illumina-based ChIP-sequencing was carried out in AcAPE1-, RNA
polymerase II- or H3K27Ac-immunoprecipitated DNA from normal growing and mitotic-arrested (by Nocodazole
treatment) A549 cells. APE1/AcAPE1-target genes are being validated by RT-PCR and promoter-directed ChIP analyses.
Results
Global gene expression analysis in APE1-knockdown A549 cells and BEAS-2B cells with ectopic expression of wild-type
(WT) APE1 or acetylation-deficient mutant K6R/K7R and consequent Ingenuity pathway analysis showed that a
significant number (â‰ˆ70%) of genes affected by APE1-knockdown/WT-APE1 overexpression are linked to cell
proliferation and cell cycle regulatory pathways. ChIP-sequencing showed AcAPE1â€™s global occupancy predominantly
localized to the regulatory regions of the putative target genes. Interestingly, binding of AcAPE1 to condensed chromatin
throughout mitosis (unpublished) prompted us to analyze its binding profile in mitotic-arrested cells. We found that there is
more than 95% overlap in AcAPE1â€™s global binding profile in interphase vs. mitotic-arrested cells. We are currently
validating a sub-set of target genes e.g., CDKN1A, CDKN1C, CDK1, CDK2, c-Myc, etc. which affect cell proliferation. It
is noteworthy that activation of these genes after mitosis is significantly impaired due to APE1 depletion. Furthermore, we
found reduced recruitment of RNA polymerase II and H3K27Ac (chromatin marker for active genes) in APE1-knockdown
cells.
Conclusion
During mitosis transcription ceases due to chromosome compaction. However, all proliferating cells must remember its
transcriptome through some unique chromatin-associated factor(s) so that the gene expression pattern is successfully
propagated to daughter cells. Our studies suggest that AcAPE1 may function as a gene bookmarking factor via binding to
the regulatory regions of target genes throughout mitosis. Requirement of APE1 for post-mitotic reactivation of these genes
affecting cell proliferation further support its bookmarking function. This is consistent with the essentiality of AcAPE1 in
cell proliferation, as also manifested by its persistent overexpression in tumor tissues.
Financial Disclosure (Shiladitya Sengupta)
No
FDA Disclosure
Cleared:Yes
Keywords
APE1/acetylated APE1
gene bookmarking
cell proliferation
lung cancer
Abstract ID: 201
Investigation Of The Role Of miR-26a In Normal Physiology And Tumorigenesis Using A Novel TET And
CRE-inducible Transgenic Mouse
Author List
1. Presenting Author: Lauren Zeitels
2. Additional Author: Joshua Mendell
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
MicroRNAs (miRNAs) are known to play important roles in cancer through their ability to regulate oncogenic and tumor
suppressor pathways. Downregulation of miR-26 family members (miR-26a and miR-26b) has been implicated in the
development and progression of hepatocellular carcinoma (HCC), B cell lymphoma, and breast cancer. Additionally,
restoration of physiologic levels of miR-26a in tumors in a mouse model of HCC as well as in B lymphoma cells halts
tumor progression. Conversely, overexpression of miR-26a accelerates tumorigenesis in a mouse glioma model.
Methods
In order to further investigate the settings where miR-26 delivery would be beneficial for cancer therapy and the potential
adverse consequences of miR-26 overexpression, we generated a mouse line harboring a doxycycline (Dox)- and
Cre-inducible transgene that co-expresses eGFP and miR-26a (Rosa26-M2rtTA; tcGm26a).
Results
Administration of Dox via drinking water causes ~8-20-fold induction of miR-26a in broad tissues in these animals
including liver, spleen, and intestine as measured by quantitative RT-PCR. Immunohistochemical staining for GFP
revealed strong expression in the liver, spleen, intestinal epithelium, pancreas, thymus, lymph node, and epidermis as well
as moderate expression in the proximal tubules of the kidney. Induction of miR-26a during embryogenesis does not result
in any overt developmental defects and induction in adults for a 4 week period is similarly well-tolerated. Unexpectedly,
we observed that mice expressing miR-26a during pregnancy fail to lactate after giving birth. Prior work has documented
that miR-26a levels in breast tissue drop during lactation and increase during late involution.
Conclusion
The mechanisms through which miR-26a regulates breast tissue function in the post-partum period and the relationship of
these functions to tumorigenesis in this tissue are currently under investigation. Moreover, experiments are underway to
utilize these animals to elucidate mechanisms of miR-26a-mediated tumor suppression in models of liver cancer and B cell
lymphoma as well as to determine the long-term consequences of miR-26a overexpression. Our latest results from these
ongoing studies will be presented.
Financial Disclosure (Lauren Zeitels)
No
FDA Disclosure
Cleared:Yes
Keywords
miRNA
liver cancer
breast cancer
None
Abstract ID: 202
Near-infrared Fluorescence Lymphatic Imaging In Metastatic Melanoma And Post-surgical Recovery
Author List
1. Presenting Author: John Rasmussen
4. Additional Author: Janice Cormier
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Fig1.jpg
Summary
Introduction
Lymphangiogenesis is increasingly recognized for its role in cancer metastasis even before metastasis occurs. However,
clinical imaging modalities with the spatial and temporal resolutions required to non-invasively image these lymphatic
changes have not been available. The evaluation and treatment for melanoma includes sentinel lymph node biopsy (SLNB)
and, when the sentinel lymph node (SLN) is cancer positive, complete lymph node dissection (CLND). Up to 60% of
CLND patients develop lymphedema, a poorly understood lymphatic disease characterized by chronic, debilitating
swelling. We recently developed near-infrared fluorescence (NIRF) imaging techniques to non-invasively image human
lymphatics following intradermal administration of microdose amounts of contrast agent. Distinct architectural and
functional differences were observed between healthy and diseased lymphatics. In this ongoing, two part FDA approved
feasibility study, we seek to use NIRF imaging of abnormal lymphatics as prognostic/diagnostic indicators of metastatic
disease and acquired lymphedema.
Methods
Eighteen melanoma subjects undergoing wide local excision and SLNB, receive intradermal injections of 25 Âµg
indocyanine green (ICG) near the tumor and in the ipsilateral limb. Additional injections are administered contralaterally as
controls. The total ICG dose is â‰¤400 Âµg. A custom, NIRF imaging system illuminates the injection sites with 785 nm
excitation light and acquires dynamic images of fluorescent lymphatics using an intensified, charge coupled device camera.
Subjects with tumor positive SLNs are longitudinally imaged three additional times, once just prior to CLND and twice
more at four month intervals. Lymphatic images are assessed and correlated to metastatic disease and to post-surgical
lymphatic recovery.
Results
Of the thirteen SLNB subjects imaged to date, the tumor-draining lymphatics were tortuous in two, dilated in two others,
and normal in seven. Five subjects had abnormal, tortuous lymphatic capillaries radiating from the tumoral injection sites,
but only the two subjects with the dilated tumor-draining lymphatics had positive SLNs and were enrolled in the
longitudinal study. The first of these had normal limb lymphatics throughout multiple imaging sessions with no evidence of
lymphedema. The second, pictured below, had fluorescent lymphatic capillaries distal the tumor prior to SLNB and
subsequently developed dermal lymphatic backflow commonly seen in subjects with lymphedema. Whether the dermal
backflow resolves or portends onset of lymphedema remains to be seen during the follow up sessions.
Conclusion
These studies indicate that abnormal lymphatic architecture, as assessed by NIRF imaging, may provide
prognostic/diagnostic indication of metastatic disease and lymphedema. Supported by the National Institutes of Health
(R01 CA128919 and U54 CA1356404).
Financial Disclosure (John Rasmussen)
No
FDA Disclosure
Cleared:Yes
Keywords
melanoma
lymphedema
near-infrared fluorescence imaging
metastasis
Abstract ID: 203
Infusion Of CD19-directed/Multivirus Specific- Cytotoxic T Lymphocytes After Allogeneic Hematopoietic Stem
Cell Transplantation For B Cell Malignancies
Author List
1. Presenting Author: Conrad Russell Cruz
2. Additional Author: Kenneth Micklethwaite
3. Additional Author: Barbara Savoldo
4. Additional Author: Stephanie Ku
5. Additional Author: Robert Krance
6. Additional Author: Oumar Diouf
7. Additional Author: Ann Leen
8. Additional Author: Rammurti Kamble
9. Additional Author: A. John Barrett
10. Additional Author: Elizabeth Shpall
11. Additional Author: Helen Heslop
14. Additional Author: Catherine Bollard
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 02:30 PM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Allogeneic hematopoietic stem cell transplant (HSCT) may increase long term disease-free survival in patients with
high-risk-B-cell malignancies, but is associated with delayed immune reconstitution contributing to viral infections and
relapse. We hypothesized that a single T-cell platform mediating both antiviral and antileukemic activity may be beneficial.
Methods
We prepared CTLs with specificities directed towards EBV/CMV/adenovirus, then engineered them to express chimeric
antigen receptors (CAR) targeting CD19 (expressed by B-cell malignancies). Donor-derived antigen presenting cells were
transduced with an Ad5f35 vector encoding CMVpp65 transgene to stimulate and expand multivirus specific T cells. After
3 stimulations, multivirus-specific T cells were transduced with a retroviral vector encoding CAR-CD19.28zeta.
Results
Safety. Six patients (2 relapsed ALL, 2 CLL, 2 CLL/Richters transformation) were infused without infusion related
toxicity. One patient (CLL/Richters) developed fever, diarrhea, and hypotension 4 weeks post T cell therapy. Findings
were consistent with ileitis at a known previous site of disease. Gut biopsy showed absence of normal and malignant B
cells and presence of infiltrating CAR-CD19.28z T cells by qPCR.
Persistence. There was an an initial rise then a decline of transduced T cells in peripheral blood 1-12 weeks following
infusion. Persistence up to 9 weeks was documented in disease sites including the gastrointestinal tract (patient 2, 55
copies/1000 ng DNA) the bone marrow (patient 1 and 3, 45 and 26 copies/1000 ng DNA 4 weeks post CTL respectively),
and in a diseased lymph node (patient 5, 32 copies/1000 ng DNA 7 weeks post CTL).
Anti-tumor activity. Transient clinical responses were seen in 3/6 patients. Patient 1 with Ph+ ALL had 4% blasts
detectable in the peripheral blood at the time of CTL infusion#1 which cleared within 2 weeks of CTL. Remission lasted 2
months at which time she received a second CTL dose. Patient became bcr abl negative but relapsed and died of disease 7
months post CTL. Patient 2 with CLL/Richters had >50% reduction of lymphadenopathy within 2 weeks of CTLs, but
following their disappearance from the peripheral blood, developed disease progression 2 months later. Patient 3 with CLL
had stable disease for 8 months.
Anti-viral activity. Patient 1 had adenovirus positivity in stool samples, which resolved without antiviral treatment. No
other patient developed viral infections post CTL.
Conclusion
These early results support the continued study of CD19CAR/trivirus-specific T cells for treating B-cell malignancies post
HSCT.
Financial Disclosure (Conrad Russell Cruz)
No
FDA Disclosure
Cleared:Yes
Keywords
hematopoietic stem cell transplant
T cell therapy
chimeric antigen receptor
multivirus T cells
Abstract ID: 204
Changes in Stiffness and Surface Modification of PDMS Affect Breast Cancer Cell Phenotypes
Author List
1. Presenting Author: Weijia Zhang
2. Additional Author: Yen Nguyen
3. Additional Author: Lidong Qin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Microdevice has the potential to revolutionize cell biology research and clinical diagnostics because of many advantages of
its small dimensional microstructures. Polydimethylsiloxane (PDMS)-based microdevice have been increasingly used as
cell culture platforms due to its material attributes of PDMS, e.g. simple fabrication, optical transparency, tunable
elasticity, gas permeability, biological inertness, and inexpensiveness. Here, we demonstrate that the surface modification
of PDMS impacts cell-substrate interaction and cell states of cancer cells.
Methods
PDMS base and curing agent were mixed at 10:1 and 100:1 separately. After a degas process, PDMS layers were cast on
cell culture plates and then cured. After subsequent treatment with oxygen plasma, the PDMS layer was incubated with
BSA, fibronectin or collagen solution for 1 h at 37C. Cells were harvested and re-suspended in cold HBSS with 2% FBS
(HBSS+), and cell numbers were adjusted to 50,000 cells/ml for antibodies staining. Isotype control antibodies were used
as the gating control.
Results
The surface coating of collagen and fibronectin on PDMS reserves cancer cell phenotypes nearly identical to the cultures
on commercial polystyrene petri dishes. The surface coating of BSA may provide a nonadhesion cell-substrate interaction
and stimulate the raise of stem cell-like subpopulation. This study clarified certain interfacial aspects of cell states on
PDMS substrates and indicated that the cell phenotypic equilibrium possibly respond to cell-to-surface interaction. In this
study, we have observed breast cancer cell behaviors on PDMS substrates and characterized the phenotypic equilibrium of
those cells on it. We recognized that these results may reflect differential biding of specific cell adhesion molecules, e.g.,
extracellular matrix proteins. For further development of PDMS-based â€œcell on a chipâ€• technology, it is a prerequisite
to understand the interactions between cultured cells and substrate and environment. We identified that breast cancer
phenotypes can be maintained at the normal fraction on fibronectin/collagen-coated PDMS substrates while promoted on
BSA-coated ones, regardless of the different stiffness of bulk PDMS materials. With this in mind, these observations
represent a first step in the development of surfaces optimized to support the function of specific cell phenotypes of
interested.
Conclusion
Overall, PDMS is a suitable substrate for culturing breast cancer cells. Nevertheless, the appropriate surface modification
rather than elastic stiffness should be taken into account for maintaining proper cell states on PDMS substrate. Proper
pretreatment is critical for on-chip microdevice cell culture to recapitulate the result obtained off-chip.
Financial Disclosure (Weijia Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
breast cancer initiating cell
Polydimethylsiloxane
cancer cell phenotype
None
Abstract ID: 205
Development Of Phosphatidylserine Binding Peptoid Through On Bead Two Color Combinatorial Cell Screen
Author List
1. Presenting Author: Jaya Matharage
2. Additional Author: Jason Stafford
3. Additional Author: Jared Hooks
4. Additional Author: Daniel Lopes
5. Additional Author: Philip Thorpe
6. Additional Author: D. gomika Udugamasooriya
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The variability of protein biomarker expression among individuals makes it very difficult to develop targeted molecular
therapy for cancer. We have developed an on-bead two-color (OBTC) combinatorial cell screening technology to directly
identify highly specific peptoid ligands for cell surface biomarkers even without knowing the target . Peptoids are
biologically acquiescent compounds with rapid and cost effective synthesis and optimization. Using this â€˜unbiasedâ€™
selection approach we identified a peptoid binding to phosphatidylserine (PS), an anionic phospholipid. PS present in the
internal surface of the plasma membrane on normal cells, but flips out in several conditions including malignant
transformation. Itâ€™s a universal biomarker in tumor endothelium and certain tumor cells.
Methods
A peptoid library of 393,216 compounds was developed on TentaGel beads and screened using OBTC assay targeting
HCC 4017 lung cancer cells, and HBEC 30KT (Human Bronchial Epithelial Cells) normal cells from the same
patient.Cancer and normal cells were stained in red and green respectively ,equilibrated with the peptoid library and
picked up the beads bound only to red cells as possible â€˜hitsâ€™. The hits were sequenced using Edman sequencing,
synthesized with a biotin tag and ascertained binding on PS using ELISA like assay. JM79, one of the compounds which
demonstrated specific binding to PS was dimerized with different linker lengths and used them in MTS assay to evaluate
its activity on HCC 4017, MDA MB 231 and PC3 cancer cell lines. HCC4017 mouse xenografts were used to evaluate
initial in vivo therapeutic potential.
Results
HCC 4017 was stained positive for PS and HBEC 30KT was negative. JM79 monomer binds to PS with high specificity
over PC (main lipid found in normal cells) . While the monomer did not show any activity, dimerization triggers a strong
cell lytic activity on all three cancer cell lines listed above with IC 50 value at low micro molar range. Initial in vivo data
suggests a considerable vascular damage on JM79 dimer treated HCC4017 mouse xenografts.
Conclusion
The OBTC assay can unbiasedly identify non-conventional biomarkers on can cancer cell surface without restricting to
protein receptors. The JM79 dimerization triggers strong cell lytic activity and peptoids may be useful as a better and
cheaper molecular class for anti-cancer drug development. We are currently working on further improving JM79 activity
and attaching imaging agent like DOTA and NOTA to use it as therognostic agent.
Financial Disclosure (Jaya Matharage)
No
FDA Disclosure
Cleared:Yes
Keywords
Peptiods
Combinatorial screen
On Bead Two Color cell assay
Phosphatidylserine
Abstract ID: 206
Basonuclin1 (BNC1): A Novel Therapeutic Target In Ovarian Cancer Identified Through Integrative TCGA-based
Functional Genomic Analysis
Author List
1. Presenting Author: Sherry Wu
2. Additional Author: Anna Unruh
3. Additional Author: Keith Baggerly
4. Additional Author: Anil Sood
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
This study aims to interrogate if basonuclin1 (BNC1), a key gene identified through integrative TCGA-based functional
genomic analysis, is a feasible target in overcoming chemo-resistance in high-grade serous ovarian cancer (HGS-OvCa).
Methods
TCGA mRNA expression and clinical response data were used to systematically identify genes associated with
chemo-resistance in patient with HGS-OvCa. Gene-specific effects were subsequently studied for selected targets in vitro.
SiRNA targeted against BNC1, a key gene identified to be associated with poor survival, was used to study the functional
role of BNC1 in chemo-resistance. Apoptosis and cell cycle analyses were carried out following silencing of BNC1 in
ovarian cancer cell lines with or without the presence of cisplatin. The effect of silencing BNC1 on the chemosensitivity of
ovarian tumor was also examined in an orthotopic mouse model of ovarian cancer developed using platinum-resistant
A2780-CP20 cell line.
Results
We identified 102 genes with increased expression in tumors from patients with chemo-resistant disease (cancer
progression within 1-7 months after surgery; chemo-resistant group: 53 cases) compared to tumors from patients with
disease progression at >3 years (chemo-sensitive group: 57 cases). BNC1, a transcription factor which regulates ribosomal
biogenesis and cell proliferation, was one of the key targets identified. Its expression was found to be increased by more
than two-fold (Agilent platform; p<0.001) in chemo-resistant tumors. A 5-fold increase in its expression level was also
observed in cisplatin-resistant A2780-CP20 and IGROV-CP20 cells compared to parental cell lines. Silencing of BNC1
increased the sensitivity of A2780CP20 cells to cisplatin treatment (IC50) with the percentage of apoptotic cells increased
from 15% (siBNC1 alone) to 43% (siBNC1 plus cisplatin). In contrast, minimal increase in the percentage of apoptotic
cells was observed in control siRNA-treated cells following cisplatin treatment (8% to 13.5%). Profound G2-cell cycle
arrest was also noted following combined siBNC1 and cisplatin (IC30) treatment (68% vs. 28%; siBNC1 plus cisplatin vs.
siControl plus cisplatin; p<0.0001). Importantly, combinational treatment of siBNC1 and cisplatin resulted in a 90%
reduction in tumor burden in chemo-resistant A2780CP20 orthotopic mouse model when compared to control siRNA plus
cisplatin treatment group (p<0.01).
Conclusion
Our results demonstrate a highly effective functional genomics approach for identifying novel therapeutic targets in
ovarian cancer. In particular, BNC1 represents an important target for enhancing chemosensitivity in ovarian tumors and its
down-regulation could lead to better clinical outcome.
Financial Disclosure (Sherry Wu)
No
FDA Disclosure
Cleared:Yes
Keywords
Chemoresistance
Ovarian cancer
TCGA
Basonuclin 1
Abstract ID: 207
Targeting Thyroid Receptor Beta In Estrogen Receptor Negative Breast Cancer
Author List
1. Presenting Author: Guowei Gu
2. Additional Author: Kyle Covington
3. Additional Author: Yassine Rechoum
4. Additional Author: Toyin Babarinde
6. Additional Author: David Mangelsdorf
8. Additional Author: Paul Webb
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 01:50 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The treatment of estrogen receptor (ER)-negative breast cancer (BC) is a major clinical problem due to the lack of useful
therapeutic targets. Nuclear receptors (NRs) are potential targets in these patients because they regulate global
transcriptional events and many already have agonists/antagonists available.
Methods
Microarray and PAM analysis. TaqMan qRT-PCR. pGIPZ lentiviral screening. MTT and soft agar. Western Blotting.
Results
The 41 NRs clustered tumors into 5 groups. For each group we selected genes representing the highest ranked
discriminators. Thyroid hormone receptor Î²(THRÎ²) was selected from group V. The expression levels of this receptor
were confirmed by qRT-PCR and Western blot analysis. Knockdown of THRÎ² in ER-negative HCC2185 cells rendered
cells more resistant to all chemotherapeutics. Similar results were confirmed in MDA-MB-453 and HCC202 cells.
Long-term culture of cells in chemotherapy decreased endogenous levels of THRÎ² suggesting that THRÎ² might influence
cell survival. Accordingly, genetic knockdown of THRÎ² in MDA-MB-453 and HCC202 cells significantly enhanced
growth in anchorage-independent soft agar and mammosphere assays. Statistical analysis in silico of published outcomes
data from ER-negative patients (Sabatier 2011) showed that patients with low THRÎ² exhibit a worse clinical outcome. To
translate these findings into the clinic, we treated cells with specific THRÎ² agonists, GC-1 and KB-141 to activate THRÎ².
Synergistic growth inhibitory effects were observed when cells were treated with GC-1 and Doc in combination.
Surprisingly, re-expression of ERÎ± protein was observed in ER-nagative cells line HCC-2185 after treatment with GC-1
and KB141. Estradiol enhanced ERÎ± transcriptional activity with GC-1 or KB141 pretreatment, suggesting that ERÎ± was
functional. Tamoxifen inhibited cell growth, but only in cells pretreated with the THRÎ² agonists, indicating that
modulation of THRÎ² may also extend hormonal therapy to this hormonally insensitive group of tumors. Overexpression of
THRÎ² and/or THRÎ² agonist treatment increased ERÎ± levels in ER-positive MCF-7 cells as well, indicating that THRÎ²
agonists might be used to modulate ERÎ± and enhance tamoxifen response and chemosensitivity.
Conclusion
Clinical targeting of NRs in ER-negative BCs is a novel strategy since they can be specifically targeted with ligands. Our
data suggest that chemotherapy response in ER-negative patients overexpressing THRÎ² is enhanced in combination with
THRÎ² agonists. Similarly, functional re-activation of ERÎ± via targeting of the THRÎ² pathway might extend hormonal
therapies to ER-negative patients, and potentially enhance tamoxifen therapy in ER-positive patients.
Financial Disclosure (Guowei Gu)
No
FDA Disclosure
Cleared:Yes
Keywords
ER negative breast cancer
chemotherapy
nuclear receptor
Thyroid hormone receptor Beta
Abstract ID: 208
Miniaturized Electron Paramagnetic Resonance Spectrometers For Detection Of Melanoma
Author List
1. Presenting Author: Payam Seifi
2. Additional Author: Charles Chen
3. Additional Author: Xuebei Yang
4. Additional Author: Aydin Babakhani
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Electron Paramagnetic Resonance (EPR) is a spectroscopy technique with widespread use in science and engineering. EPR
is sensitive to presence of atoms or molecules with unpaired electrons, i.e. paramagnetic species. In the presence of an
external magnetic field, transition of electron spins from one quantum state to a higher or a lower state is accompanied by
an absorption or emission of electromagnetic energy, respectively. This is the basis for EPR operation, which provides
valuable information regarding the nature and surrounding microenvironment of paramagnetic molecules. Melanin, due to
its free-radical-trapping properties, is one such molecule. Detection and imaging of melanoma is therefore possible using
EPR techniques
Methods
We are developing miniaturized EPR systems for detection of melanoma. The miniaturization is achieved by eliminating of
the bulky components that are typically used in current spectrometers: microwave sources, amplifiers, mixers, etc. Using
Complementary Metal Oxide Semiconductor (CMOS) technology, integrated circuits are designed to implement full EPR
circuitry in a single electronic chip. Planar resonators and compact permanent magnets are being developed, suitable for
detection of paramagnetic species on a surface (e.g. skin).
Results
We are performing tests with phantoms made of 2,2-diphenyl-1-picrylhydrazyl (DPPH), gamma-irradiated fused quarts, as
well as synthetic melanin. Initial results have been promising, indicating feasibility of use of EPR in detecting small
amounts of paramagnetic molecules.
Conclusion
CMOS-based miniaturization provides a transition route for EPR spectroscopy and imaging technology for use in clinical
setting for detection and study of melanoma.
Financial Disclosure (Payam Seifi)
No
FDA Disclosure
Cleared:Yes
Keywords
Electron Paramagnetic Resonance
CMOS
Free Radicals
Melanoma
Abstract ID: 209
Working With The Local Supermarket To Bring Cancer Prevention Information And Encouragement To Rural
Communities
Author List
1. Presenting Author: Conrad Lyford
2. Additional Author: Barent McCool
3. Additional Author: Eric Belasco
4. Additional Author: Barbara Pence
5. Additional Author: Audrey McCool
6. Additional Author: Tyra Carter
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Developing the supermarket as a location for primary cancer prevention is a logical next step, especially for sparsely
populated and underserved rural communities. Supermarkets are where many key food and other health-related choices are
made, and supermarkets commonly serve as a place frequented by the vast majority of community residents. Supermarkets
can serve as a key source for primary preventive education for two key main types of cancer-causing behavior: obesity and
excessive sun exposure. This project is designed as a community-based partnership with United Supermarkets, LLC, a
supermarket chain with stores located in rural West Texas communities. In addition, a focus was developed to reduce
tobacco use. This proposed presentation focuses on the method developed and will provide statistical information on its
overall effectiveness as part of an overall community-wide effort to improve cancer knowledge and behavior.
Methods
This project develops an integrated message for primary cancer prevention by combining overall community health
messages and targeted messages in the supermarket. Specific items were targeted to cut your risk, boost your health where
consumers are encouraged to choose healthier food products over relatively unhealthy products. At the same time,
supporting information was presented through community food demonstrations, newspaper articles and the web. 
 
The impact of interventions and demographic factors on stated and revealed food and nutrition preferences and attitudes
are evaluated using multinomial logit and ordered logit models. The responses in initial and post-intervention surveys are
compared to detect a difference between the time periods in both the control and intervention communities. 
Results
At this point, the project has been ongoing for a year and a half, and data collection on project impact has recently been
completed. Analysis is being completed on the effectiveness of community health promotion and store communications
that have been developed including shelf talkers, signs, food demonstrations, and community presentations.
Conclusion
In this project, an integrated approach to accomplish primary cancer prevention in a community context was developed.
This approach will be put together into a package to be used by other communities to use in preventing cancer. This project
is designed to reach the underserved rural population, including rural cancer survivors, and provide them with a supportive
environment that incorporates preventive information and nutritious food access.
Financial Disclosure (Conrad Lyford)
No
FDA Disclosure
Cleared:Yes
Keywords
primary prevention
community intervention
obesity
supermarket
Abstract ID: 210
Utilization Of A Mobile Mammography Unit To Reduce Geographic Barriers To Breast Cancer Screening In Bexar
County, Texas
Author List
1. Presenting Author: Sadaf Rafique
2. Additional Author: Katherine Diaz
3. Additional Author: Anna McAndrew
4. Additional Author: Camerino Salazar
5. Additional Author: Matthew Smith
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
In Bexar County, Texas, breast cancer remains the most common form of malignant neoplasm and a leading cause of death
among women. Regular screening and early detection remains the most effective method of reducing breast cancer
mortality. In South Texas, prevalence data indicates that only 67% of women ages 40 and older have had a mammogram
within the past two years. Evidence suggests that adherence to mammography screening can be compromised by an often
complex set of socioeconomic, interpersonal, and system-related factors. 
 
To maximize the benefits of this evidence-based clinical preventive service, the Bexar County Hospital District (dba)
University Health System in partnership with UT Medicine implemented a mobile mammography screening program.
Based on clinical screening guidelines as outlined by the American Cancer Society, the focus of this effort is to facilitate
access to screening services by reaching various segments of eligible women (i.e., economically underserved or uninsured)
through on-site screening events held at community, workplace, and faith-based venues. Partnerships between healthcare
systems and local community partners can enhance the opportunity to provide safe, timely, and efficient care to
populations most in need.
Methods
Prior to implementation, a planning framework was developed to assist clinical, information system, and administrative
staff to adopt appropriate screening, diagnostic, and referral guidelines as outlined by the American Cancer Society.
Deployment process maps were developed that identified staff activity and responsibility during the screening process.
Statistical process control charts were used to chart turnaround time for screening and diagnostic exams. A patient
experience survey was also administered to assess quality of service delivered. Geospatial analysis was undertaken to chart
both location and reach of screening services throughout Bexar County.
Results
As of July 2012, a total of 1,827 women have been screened, of which 340 (19%) required additional testing, 43 required
biopsies, and 8 were diagnosed with breast cancer. Pertaining to patient experience with screening services received on the
mobile unit, the vast majority (93%) of respondents conveyed a very positive experience. Geospatial analysis of women
screened by median household income indicate improved reach for populations residing in economically distressed areas of
the city.
Conclusion
With an average of 20 mammography screenings per community event, such efforts have made breast cancer screening
more convenient and accessible for women across Bexar County. This translates into lives saved through early detection
and cost-savings to both the healthcare delivery system and the local community.
Financial Disclosure (Sadaf Rafique)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast Cancer
Community Outreach
Economically Underserved
Safety Net Providers
Abstract ID: 211
Dose Reduction Strategies For Low-risk Rhabdomyosarcoma: Using Cost Comparisons To Choose Between Two
Chemotherapy Regimens With Similar Outcomes
Author List
1. Presenting Author: Heidi Russell
2. Additional Author: Michael Swint
3. Additional Author: David Walterhouse
4. Additional Author: Douglas Hawkins
5. Additional Author: Brooke Bernhardt
6. Additional Author: Fatih Okcu
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Slide1.jpg
Summary
Introduction
Deciding between two treatment strategies with similar clinical outcomes requires consideration of other aspects of
treatment. Comparing costs may be particularly valuable when the treatment strategies differ in the demands they place on
the health care system and on the patients/families. Yet only a few very limited cost comparisons have been performed in
childhood cancer. Successful historic treatment of low-risk rhabdomyosarcoma prompted sequential Childrenâ€™s
Oncology Group Trials using different strategies for reducing chemotherapy intensity: D9602 Subset 1 delivered 46 weeks
of outpatient vincristine and actinomycin D whereas ARST0331 delivered these two agents over 24 weeks and added 4
doses of cyclophosphamide. We undertook a comprehensive cost comparison of these two treatment strategies to help
guide future decision-making.
Methods
We modeled a representative patient from aggregate clinical trial data to address the costs of treatment from the healthcare
perspective. All study-required medical care was included: chemotherapy, supportive medications, laboratory studies, and
imaging studies during treatment. Likelihood of transfusion, infection, or neuropathy was estimated from clinical trial
reports and focused chart review. Costs of radiation, surgery and off-therapy surveillance were excluded. Unit costs were
obtained from literature and national reimbursement and inpatient utilization databases: Average Wholesale Price, Center
for Medicaid Services, and Kidsâ€™ Inpatient Database. Outcome measures were event-free survival and monetary costs
(2012 US dollars).
Results
Survival is similar between strategies. The contributions of treatments and supportive care are presented in table form.
Chemotherapy costs were higher for D9602. Inpatient costs were only incurred for ARST0331. The higher cost of
supportive drugs on ARST0331 included mesna (50%) and hematopoietic growth factor support (32%). Longer overall
treatment time contributed to the higher costs of laboratory tests and imaging studies for D9602. Parameter uncertainty
assessment with probabilistic sensitivity analysis is pending.
Conclusion
Cost analysis suggests that ARST0331 may be more cost effective than D9602 from the healthcare systemâ€™s
perspective; sensitivity analysis is needed to confirm this finding. The familyâ€™s perspective of these regimensâ€™ costs
may differ because, while ARST0331 is shorter, its intensity may put greater restrictions on activities of daily living such
as school attendance. A separate formal analysis is pending. Attention to the services driving the costs provides directions
for future efficiency improvements.
Financial Disclosure (Heidi Russell)
No
FDA Disclosure
Cleared:Yes
Keywords
Rhabdomyosarcoma
Child
Cost
Comparative effectiveness
Abstract ID: 212
Challenges In Breast Imaging And Spectroscopy At 7 Tesla
Author List
1. Presenting Author: Sergey Cheshkov
2. Additional Author: Ivan Dimitrov
3. Additional Author: Sally Goudreau
4. Additional Author: Stephen Seiler
6. Additional Author: Mary McDougall
7. Additional Author: Steven Wright
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Picture22.jpg
Summary
Introduction
Concentration of various metabolites in breast tissue may be important in understanding risk factors for breast cancer and
for assisting with diagnosis and therapeutic monitoring. For example, certain dietary fatty acids have been associated with
increased risk of breast cancer, and the presence of choline has been proposed as a diagnostic marker of malignancy.
Magnetic resonance spectroscopy offers the potential for completely noninvasive monitoring of these metabolites.
However, detection of these metabolites is difficult at conventional clinical field strengths (1.5 or 3.0 Tesla). This project is
a joint effort between Texas A&M University (TAMU) and UT Southwestern (UTSWMC) to design and construct
radiofrequency (RF) coils that are suitable for breast imaging and optimized for spectroscopy at 7T, since conventional coil
designs suffer from inhomogeneous RF energy distribution at 7T.
Methods
Two approaches have been taken to overcome RF inhomogeneity. First, a novel coil design, termed â€œforced current
excitationâ€• (FCE), was developed at TAMU using a combination of computational modeling and construction of coils for
bench testing. The FCE uses transmission line properties to ensure equal coil element currents despite unequal loading,
coupling, or coil sizes. Second, an upgrade of the 7T Philips scanner at UTSWMC in mid-2012 to parallel transmit
capabilities allows independent computer control of RF energy in two coils.
Results
Studies in healthy subjects and patients (protocol approved by the UTSWMC IRB) using TAMU-built unilateral
1H FCE breast coils included T2 weighted and fat-suppressed 3D T1 weighted
imaging, and single voxel spectroscopy of fat and grandular breast tissues. The FCE technique provides uniform excitation,
free of high field artifacts, and enables acquisition of excellent high-resolution fat-suppressed breast images that provide
significant morphological details. An example of breast cancer imaged at 7T is shown in Figure 1 and the corroborating
choline spectrum from this malignancy is shown in Figure 2. We have also devoted considerable effort to 13C
spectroscopy, since it carries additional metabolic information, such as omega-6/omega-3 ratio and trans-fat profile.
However, acquisition of useful 13C spectra introduces another challenge, the requirement for 1H
decoupling. The FCE design has proven suitable; an example of broadband proton-decoupled 13C NMR
spectrum of healthy breast is shown in Figure 3.
Conclusion
Pilot studies in healthy women and patients with breast cancer demonstrate that 1H imaging, 1H
spectroscopy and proton-decoupled 13C spectroscopy are all feasible at 7T. Further technical development
will undoubtedly improve data quality and ease-of-use. Multiple channel transmission is also particularly promising.
Financial Disclosure (Sergey Cheshkov)
No
FDA Disclosure
Cleared:Yes
Keywords
high field MR
breast imaging and spectroscopy
cancer
choline
Abstract ID: 214
Providing Accessible Cancer Survivorship Education To Texans
Author List
1. Additional Author: Sarah Gomez
2. Presenting Author: Athan Schindler
3. Additional Author: Stephanie Nutt
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Chart1.jpg
Summary
Introduction
Since 2004, LIVESTRONG has provided free community-based navigation services to those affected by
cancer, over the phone and online, in English and Spanish. These navigation services include education, emotional support
and resource finding. In 2010, LIVESTRONG opened The LIVESTRONG Cancer
Navigation Center (LCNC), to provide these services face to face to those in Austin and the surrounding counties. In 2012,
the LCNC started hosting Community Education and Discussion Forums (CEDF), in-person and online, to further support
cancer survivors throughout their cancer journey.
Methods
The CEDF are available to attend in-person or virtually. The online format was crucial to the development of the CEDF
because transportation is a barrier to the majority of the constituents that LIVESTRONG serves. The
CEDF are promoted via direct referrals, flyers, emails, and Facebook/Twitter postings. The topics selected for the
educational series were based on needs received in survey responses from constituents. The speakers are experts in their
field that work in and around the Austin area.
Results
Across the 5 CEDF that have been held in 2012, 65 attendees have come in person and 272 attendees have viewed the
classes online (via livestreaming). Out of these participants, a total of 90 people completed evaluations (both in person and
online). Eighty-nine percent of respondents were very satisfied or satisfied with the class; another 9% were unsure. Across
4 of the CEDF: 86% strongly agreed or agreed that LIVESTRONG cancer support information and
services helped me address concerns about cancer. 78% strongly agreed or agreed that the class positively impacted my
cancer experience. Statement PercentageÂ / Strongly agreed/agreed
- The web format was appropriate for this topic / 94% - The web format and chat function allowed me to interact in the
class as much as I wanted to / 90% - I would use this web format to participate in other LIVESTRONG
classes in the future / 97%
Conclusion
Based on feedback received in the evaluations LIVESTRONG will continue to provide the CEDF
in-person and online, while investigating the potential of providing online classes to their Spanish audience in 2013. By
continuing to provide these educational series in these different formats, LIVESTRONG will strive to
eliminate barriers to education for all cancer survivors.
Financial Disclosure (Sarah Gomez)
No
FDA Disclosure
Cleared:Yes
Keywords
Community Educational Series
Austin Cancer Survivors
Access to education
Online Promotion
Abstract ID: 215
Breast Cancer Biomarkers From Biosimulations: Transcriptome-to-Reactomeâ„¢ Technology
Author List
1. Presenting Author: Richard Le Baron
2. Additional Author: Greg Villareal
3. Additional Author: Dawnlee Roberson
4. Additional Author: Clyde Phelix
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
CPRIT-Fig1_LeBaron_2012.jpg
Summary
N/A
Introduction
Genome-wide gene-expression profiles, transcriptomes, from microarray tests are used for clinical decision-making; novel
uses of transcriptomes will continue to emerge. We are commercializing a patent-pending technology using transcriptomes
to determine parameters for deterministic-kinetic models of biological pathways, Transcriptome-To-Reactomeâ„¢
(TTRâ„¢):Transforming Growth Factor (TGF)-Î² Signaling. We demonstrate how biosimulation results for proteomics,
flux, and a derivative property of the network system can be utilized as biomarkers for breast cancer.
Methods
The TGFÎ² Signaling Model was accessed from ReactomeÂ®.org; manual curation was performed to add
beta-induced-gene-human-clone-3 (BIGH3) as a target gene for Smad transcription factors. Biosimulations were run with
COPASIÂ®. Transcriptomes were accessed from NCBI GEO archives (GSE27562), where peripheral blood mononuclear
cells (PBMC) were collected from women with suspect initial mammograms, prior to undergoing diagnostic biopsy to
differentiate benign from malignant cases. PBMCs were also collected from women with normal initial mammograms as
negative controls. Ten individual TTRâ„¢-biosimulations were run in each category. Candidate biomarkers were identified
by differences in simulated proteomic levels, reaction fluxes, and sensitivities analyses of simulated reactions. A 10 fold
cross over design for training and testing data sets was used to assess biomarker candidates, a TGFÎ²1-receptor complex,
Smads, and slope of the target gene expression flux. We followed industry and clinical standards for assessing biomarkers,
i.e., sensitivity, specificity, positive and negative predictive values (PPV, NPV), accuracy, receiver operator characteristic
(ROC) curve and area under ROC curve (AUC).
Results
Sensitivities analyses showed differences between control and benign versus malignant biosimulation reactions. Ten
reactant-reaction sensitivities were greater in malignant versus both control and benign categories. The
TGFÎ²1:type-II-receptor:Phospho-type-I-receptor:SARA-complex was selected for analysis as a biomarker; also the
reaction for BIGH3 expression was identified and the slope of the rising phase of the TGFÎ²1-mediated BIGH3 expression
was assessed; as were Smad3 and Smad4 levels. For predicting malignancy versus control, accuracy was 0.60, 0.85, 0.80,
and 0.90; sensitivity was 0.30, 0.90, 0.70, and 0.80; specificity was 0.90, 0.80, 0.90, and 1.00; PPV was 75%, 82%, 88%,
and 100%; NPV was 56%, 89%, 75%, and 83%; AUC was 0.60, 0.77, 0.72, and 0.82, respectively. These biomarkers were
effective for predicting benign versus control, but worse for distinguishing malignant from benign classifications.
Conclusion
Our TTRâ„¢ Method is validated for identifying candidate biomarkers for cancer. This retrospective study satisfies the
requirement for this phase of discovery and evaluation of cancer biomarkers. Prospective studies are needed for successful
commercialization. Our technology will advance Individualized Medicine.
Financial Disclosure (Richard Le Baron)
material? Yes
- AL Phahelix Biometrics, Inc.
FDA Disclosure
Cleared:Yes
Keywords
biomarkers
breast
diagnostic
predictive biosimulation
Abstract ID: 216
Success Factors In Developing A Survivorship Clinic For Adolescents & Young Adults
Author List
1. Presenting Author: Christopher Hamilton
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
AYAposterHamilton.jpg
Summary
N/A
Introduction
With current advances in cancer care, most of the children, adolescents, and young adults (AYA) diagnosed with cancer
will be long term survivors. As young survivors transition from diagnosis and treatment to survivorship, they have unique
needs for health education, screening and surveillance, management of late effects, as well as psychosocial, financial, and
educational needs. These young survivors often lack medical homes and many do not have survivorship plans. Community
based survivor clinics offer a medical home as well as specialized care focusing on the unique needs of cancer survivors.
Methods
Through a grant from LIVESTRONG and the Aragona Family Foundation, the Seton Healthcare Family opened the Seton
Cancer Survivor Center, the first to care for cancer survivors 18 to 39 in Central Texas. The Center provides a continuum
of medical, physical, and emotional survivorship services for AYAs. The Center also provides transition services for
childhood cancer survivors that are maturing out of the LIVESTRONG Childhood Cancer Survivorship Center at Dell
Childrenâ€™s Medical Center.
Results
The clinic is staffed by an internal medicine physician and RN navigator familiar with and trained in the unique needs of
the AYA population including late effects. The clinic is open to all AYA survivors in Central Texas, whether treated at
Seton or other institutions. Survivors are provided a comprehensive treatment summary and survivorship plan. The
navigator connects patients to needed and accessible medical and psychosocial resources in the community and works
closely with the LIVESTRONG Navigation Center.
Conclusion
There are several critical success factors that lead to the development of an adolescent and young adult cancer
survivorâ€™s center. A physician and practice that are interested in providing survivorship services is the first and
fundamental building block. Support by senior leadership from the hospital or healthcare system help ensure program
success through providing resources, including funding commitments. A provider community that recognizes the benefits
of cancer survivorship and long term follow up is necessary to drive referrals to the center. Marketing and outreach to
survivors and their friends and families through social media supports self referrals to the clinic. Patient navigation is an
integral part of care, helping to link patients to the myriad medical and psychosocial resources that are needed after cancer
treatment. Lastly, an infrastructure that can be adapted or modified to include a survivorship clinic helps to smooth the
transition from cancer treatment to survivorship.
Financial Disclosure (Christopher Hamilton)
No
FDA Disclosure
Cleared:Yes
Keywords
Survivorship
Adolescent and Young Adult
Navigation
Medical Home
Abstract ID: 219
Mass Spectrometry-Based Method For Mapping Protein Cysteine Oxidation
Author List
1. Presenting Author: Chia Fang Lee
2. Additional Author: Tanya Paull
3. Additional Author: Maria Person
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Reactive oxygen species (ROS) play important roles in normal biological functions and pathological processes. Cancer
cells are frequently under persistent oxidative stress due to oncogenic stimulation, increased metabolic activity, and
mitochondria malfunction. Elevated levels of ROS in cancer cells serve as an endogenous source of DNA-damage agents
that promote genetic instability. Cysteine is the most oxidant-sensitive commonly coded amino acid and may undergo
many oxidative modifications, including cysteine sulfenic acid (R-SOH), sulfinic acid(R-SO2H), and sulfonic
acid(R-SO3H). Here we describe an approach to detect cysteine oxidation without additional enrichment steps using a
mass spectrometry-based strategy.
Methods
The method was initially optimized using in vitro oxidized BSA. BSA was incubated with different concentrations of
hydrogen peroxide, then digest with trypsin. Samples containing 1.5 pmol of peptides were resolved by using a 65min LC
gradient on a high resolution chromatographic separation with a long nano-column and analyzed by Orbitrap Elite mass
spectrometer. To ensure confident identification of oxidative modifications, both MS1 and MS2 were acquired in the
Orbitrap with high resolution and high mass accuracy. One scan cycle included an MS1 scan (m/z 300-2000) at a
resolution of 120,000 followed by 10 MS2 scans at a resolution of 15,000 by both CID and HCD to fragment the five most
abundant precursor ions found in the MS1 spectrum.
Results
Results show that the sequence coverage of BSA was 80% which contains 29 cysteines with false discovery rate (FDR) 5.
In total we identified 17 cysteine oxidative modifications on 13 cysteine residues, including 3 cysteine sulfenic acid, 7
sulfinic acid, and 7 sulfonic acid. The results were also further analyzed by Skyline to quantitate the changes between
different oxidation statuses.
Conclusion
This approach allowed us to identify low abundance modified peptides in the digest mixture without prior enrichment and
to find oxidation sites on proteins that will help elucidate the role of oxidative stress in the process of carcinogenesis.
Financial Disclosure (Chia Fang Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
Cysteine oxidation
mass spectrometry
Quantitation
None
Abstract ID: 220
A Nonribosomal Peptide Antibiotic, Occidiofungin, Triggers Apoptosis In Fungal Cells
Author List
1. Presenting Author: James Smith
2. Additional Author: Akshaya Ravichandran
3. Additional Author: Shien Lu
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
There is a need to identify new antifungals for the treatment of serious fungal infections. Given an increasing population of
immunocompromised individuals, in particular those undergoing treatment for cancer, fungal infections lead to debilitative
illnesses and these patients have a high mortality rate. A substantial amount of work has been done to characterize an
antifungal we named occidiofungin. Current studies support investigational studies aimed at determining occidiofungin's
therapeutic potential for the treatment of life threatening fungal infections. A detailed structural analysis, spectrum of
activity, and animal toxicity studies have been performed on occidiofungin. From these studies, occidiofungin has been
determined to be rapidly fungicidal at submicromolar concentrations, has a broader spectrum of activity than other
clinically used antifungals, and has a minimal toxicological effect in an animal study. Occidiofungin produced by the soil
bacterium Burkholderia contaminans MS14 is a nonribosomally synthesized cyclic peptide having a base mass
of 1200.39 Da. Currently, the mechanism of action (MOA) of occidiofungin is not known. Its MOA in the fungal cell was
found to be different from that of the common classes of antifungals such as azoles, polyenes and echinocandins.
Hypothesis: Occidiofungin triggers an apoptotic or autophagic pathway in the fungal cell, leading to cell
death.
Methods
Saccharomyces cerevisiae viability, TUNEL and ROS detection assays were used to characterize the effect of
occidiofungin on yeast cells.
Results
When viewed under Olympus confocal microscope (40x/0.90 dry objective), S. cerevisiae cells appeared to have shrunk in
size and showed the presence of "dancing bodies" at low drug concentrations (1Î¼g/ml). Dancing bodies are polyphosphate
molecules which are seen in the vacuole of yeast cells before apoptosis and cell death. TUNEL and ROS detection assays
revealed an increase in fluorescence with increasing concentrations of the antifungal. A screen carried out on
Saccharomyces cerevisiae gene deletion mutants in the apoptotic and autophagy pathways identified the
apoptotic gene, Î”yca1, as having a 2-fold increase in resistance. Autophagy mutants had no difference in sensitivity
compared to the wild-type control.
Conclusion
Experiments presented demonstrate that the MOA for occidiofungin in yeast is different from that of the common classes
of antifungals used in the clinic, such as azoles, polyenes, and echinocandins. Our study shows that the induction of
apoptosis is the mechanism of action of occidiofungin in yeast cells.
Financial Disclosure (James Smith)
material? Yes
- Sano Chemicals
FDA Disclosure
Cleared:Yes
Keywords
Antifungal
Mechanism of Action
Apoptosis
Peptide
Abstract ID: 221
Rapid And Sensitive Detection And Confirmation Of Clinically Actionable Mutations In Tumor Biopsies Using
Orthogonal Next Generation Sequencing Technologies
Author List
1. Presenting Author: Gary Latham
2. Additional Author: Andrew Hadd
3. Additional Author: Elizabeth Mambo
4. Additional Author: Liangjing Chen
5. Additional Author: Sachin Sah
6. Additional Author: Jeffrey Houghton
7. Additional Author: Kalyan Buddavarapu
8. Additional Author: Tiffany Sanford
9. Additional Author: Dennis Wylie
10. Additional Author: Adam Marko
11. Additional Author: Ashish Choudhary
12. Additional Author: Alex Adai
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Individualized cancer treatments promise improved patient outcomes through targeted therapeutics. These therapies require
an accurate inventory of the genetic changes in tumor-specific molecular pathways that may be clinically actionable using
approved anticancer drugs or those in clinical trials. Next Generation Sequencing (NGS) has emerged as an enabling, high
throughput technology that can identify â€œdruggableâ€• gene alterations in cancer. 
 
Methods
We developed and commercialized a set of cross-platform, high sensitivity, low input, and FFPE-compatible multiplex
PCR enrichment and analysis methods that provide rapid and reliable NGS of clinically relevant mutations in both
oncogenes and tumor suppressor genes. WAsuragenâ€™s SuraSeqâ„¢ PCR panels target 5, 16, or 52 cancer genes and up
to 7500 known mutations. These panels were compared and contrasted across Illumina and Ion Torrent NGS instruments,
and with other commercial panels such as the AmpliSeqâ„¢ cancer panel (Life Technologies). Variant calling was
accomplished using novel methods that accommodated the challenging sample characteristics of FFPE DNA. 
Results
We established the detection of low-level mutations from >100 FFPE and fine needle aspiration (FNA) samples per NGS
run sequenced at >1000x coverage. Empirical testing of residual clinical samples revealed the unique features of variant
â€œnoiseâ€• in FFPE sample cohorts, leading to the development of optimized algorithms with high PPV and sensitivity.
Evaluation of a well characterized set of 38 colon cancer FFPE samples demonstrated 99% agreement between SuraSeqâ„¢
PCR enrichment followed by NGS, and two independent reference mutation assays. Importantly, multiplex mutation
standards were quantified with high correlation (R2>0.90) between distinct enrichment workflows on the sameâ€”and
differentâ€”NGS platforms. Last, we developed an on-demand mutation confirmation strategy that allowed variants called
on one NGS instrument (Illumina) to be validated by evaluation using a distinct NGS chemistry (Ion Torrent), and
demonstrated the value of this approach in detecting low abundance mutations compared to Sanger sequencing. 
Conclusion
The development of robust and highly sensitive NGS of clinically actionable mutations in tumor biopsy DNA requires
quantitative reference materials, incremental QC metrics and bioinformatic algorithms tuned to accommodate the elevated
sequence-specific background observed in FFPE samples. The results of our study highlight the potential for rapid and
routine detection of â€œdruggableâ€• mutations in clinically relevant tumor samples that can address current limitations in
cancer molecular diagnostics, including the confirmation of detected variants across platforms.
Financial Disclosure (Gary Latham)
material? Yes
- Asuragen
- Asuragen
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 222
Novel Therapeutic Targets In Inflammatory Breast Cancer: Can We Target The Cell Cycle?
Author List
1. Presenting Author: Angela Alexander
2. Additional Author: Cansu Karakas
3. Additional Author: Yun Gong
4. Additional Author: Ricardo Alvarez
5. Additional Author: Naoto Ueno
6. Additional Author: Khandan Keyomarsi
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Inflammatory breast cancer (IBC) is a rare, but highly aggressive form of breast cancer, accounting for 2-5% of all breast
cancers in the US. Unfortunately, until recently this disease has not been studied extensively at the molecular/cellular level
despite the compelling unmet need to develop more effective therapies. In spite of receiving aggressive multidisciplinary
therapy (anthracycline-taxane-based neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiation
therapy), only about 40% of IBC patients survive 5 years. The goal of this project is to identify new targets that can be
exploited pharmacologically either in combination with current therapies or with other novel agents. Gene expression
studies performed so far have not identified any robust new potential targets for therapy, so we sought to determine
whether non-IBC specific proteins could also be targeted in IBC. 
 
Previous work from our laboratory has identified tumor-specific low molecular weight forms of cyclin E, termed LMW-E
that are preferentially found in triple-negative breast cancers and serve as a poor prognostic biomarker. As a result of
cleavage, LMW-E preferentially accumulates in the cytoplasm where it exerts its pleiotropic oncogenic functions including
deregulating the cell cycle. Furthermore, cells harboring LMW-E are sensitive to CDK inhibitors.
Methods
To establish the clinical relevance of targeting the cyclin E/CDK2 axis is IBC, a pilot study was performed to determine
the incidence of LMW-E in IBC tumors. We performed IHC on 11 post-chemotherapy surgical specimens from MD
Anderson. 
 
In addition, IBC cell lines, SUM149 and KPL4, which express LMW-E were treated with a panel of CDK2 inhibitors to
determine their sensitivity in both short-term and long-term assays. The long-term assay we developed, the
high-throughput survival assay was used to examine combinations of agents for potential synergies using isobologram
analysis.
Results
All tumors expressed cyclin E, 8 of which had predominantly cytoplasmic staining, indicative of LMW-E expression.
These promising preliminary results led us to perform in vitro experiments to determine sensitivity to CDK2 inhibitors and
characterize cell cycle profiles.
Several synergistic combinations of drugs have been identified and are currently being screened, in order to prioritize
clinically-relevant agents to move forward with in vivo studies. Using PI staining and FACS analysis, we have
demonstrated that similar to non-IBC cell lines, CDK2 inhibitors induce a potent G2/M arrest, leading to cell death by
mechanisms which are currently being investigated. 
Conclusion
Taken together these studies provide solid proof of concept that targeting CDK2 is a promising strategy in treating IBC.
Financial Disclosure (Angela Alexander)
No
FDA Disclosure
Cleared:Yes
Keywords
Cell cycle
IBC
Combinatorial therapy
CDK2
Abstract ID: 223
Ubiquitin Carboxyl-terminal Esterase L1 (UCHL1) In Regulating Processes Involved In Neuroblastoma
Pathogenesis Of Cancer Stem-Like Cells.
Author List
1. Presenting Author: Judy Chang
2. Additional Author: Anne Romeo
3. Additional Author: Patricia Sanchez-Diaz
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood cancers. Long-term survival of patients
with advanced disease is <40%, and over half relapse. Recent studies suggest that many cancers contain a small reservoir
of cells that have been shown to be responsible for cancer maintenance. These cells display stem-like properties and may
be an underlying cause for cancer relapse. Therefore, targeting this cancer stem-like cell (CSC) fraction could lead to
improved therapies. Recent studies have indicated that deubiquitinating enzymes (DUBs) are involved in cancer-associated
pathways. Previous work identified that ubiquitin carboxyl-terminal esterase L1 (UCHL1) was differentially expressed in
the enriched CSC fraction of human NB cell lines, suggesting a potential link between UCHL1 and CSCs. UCHL1 has
been proposed to have either oncogenic or tumor suppressive properties depending on the cellular context. The hydrolase
activity has been implicated in promoting oncogenic processes such as cellular proliferation, invasion, and migration. The
objective of our study is to determine the effect of inhibiting UCHL1 hydrolase activity on NB pathogenesis and CSC
maintenance.
Methods
We performed in vitro analyses in the NB cell line, SK-N-BE(2). Sphere formation assay was used to enrich for the CSC
population. We validated UCHL1 gene and protein expression in monolayer and neurospheres (CSC fraction) by real-time
qRT-PCR and western blot respectively. We used the small molecule inhibitor, LDN-57444, to block UCHL1 hydrolase
activity. This effect on sphere formation (read-out for self-renewal) and cellular viability was determined by quantification
of spheres and MTS assays respectively. The cell cycle distribution of neurospheres in the presence of LDN-57444 was
then analyzed. Next, selected genes of the Wnt/Î²-catenin pathway were validated by real-time qRT-PCR. Finally,
anchorage independent growth and cellular invasiveness of LDN-57444 treated SK-N-BE(2) monolayers were evaluated.
Statistical significance was determined by Studentâ€™s t-test, and p-values < 0.05 were
considered significant.
Results
We observed a two-fold higher expression of UCHL1 in the CSC population. Inhibition of UCHL1 hydrolase activity
indicated impaired sphere formation and reduced cellular viability in a dose-dependent manner. Cell cycle analysis of
LDN-57444 treated neurospheres demonstrated an increase in the number of S-phase cells. We further validated reduced
mRNA expression of MYC, MYCN, and CTNNB1. In the monolayer, inhibiting
UCHL1 hydrolase activity diminished colony formation and cellular invasiveness.
Conclusion
Our data suggests that UCHL1 is potentially an important factor in tumor cell survival, specifically the CSC fraction, and
NB pathogenesis.
Financial Disclosure (Judy Chang)
No
FDA Disclosure
Cleared:Yes
Keywords
UCHL1
cancer stem cells
neuroblastoma
Wnt/Beta-catenin pathway
Abstract ID: 224
In Vivo Significance Of Mdm4 And P73 Interaction In Development And Tumorigenesis
Author List
1. Presenting Author: Mehrnoosh Tashakori
2. Additional Author: Elsa Flores
3. Additional Author: Guillermina Lozano
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The tumor suppressor protein p53 is negatively regulated by the Mdm proteins. The significance of Mdm2 and Mdm4 in
regulation of p53 was determined from mouse models. The Mdm2-null mice die at E3.5 while
Mdm4-deficient mice die at E7.5. Both embryo lethalities are completely rescued by deletion of
p53. p73, a member of the p53-family, is a transcription factor with tumor suppressor activity. Both Mdm
proteins and p73 directly interact via their N-termini. Isothermal titration calorimetry revealed that the affinity of p53 and
p73 for Mdm is similar while p73 has a higher affinity for Mdm4. To investigate the physiological importance of the
Mdm4 and p73 interaction, we asked whether Mdm4 is also a negative regulator of p73 in vivo.
Methods
To address this question, I am studying whether the embryonic lethality of Mdm4 deficient mice is rescued by
p73 loss and I will analyze the phenotype of Mdm4âˆ†2/âˆ†2 p73âˆ’/âˆ’
mice at different developmental time points to determine rescue. Additionally, I will perform gene-dosage experiments to
determine the contribution of both p53 and p73 in the Mdm4-null phenotype. I have
set up crosses to determine whether the Mdm4âˆ†2/âˆ†2 p53+/âˆ’
p73+/âˆ’ or Mdm4âˆ†2/âˆ†2 p53+/âˆ’ p73âˆ’/âˆ’
mice are developmentally more advanced as compared to Mdm4âˆ†2/âˆ†2 p53+/âˆ’
embryos or viable. Lastly, I will examine the role of Mdm4 overexpression in combination with p73
haploinsufficiency in tumor development.
Results
Preliminary data indicate that p73 loss partially rescues Mdm4 null lethality at E9.5. Our analysis
at E13.5 has shown that deletion of p73 does not rescue Mdm4 deficient embryonic lethality to
this stage of development. Currently we are investigating such rescue at E11.5. Studying the effect of p53 and
p73 gene dosage on Mdm4 null embryonic lethality, we found that
Mdm4âˆ†2/âˆ†2 p53+/âˆ’ p73+/âˆ’ or
Mdm4âˆ†2/âˆ†2 p53+/âˆ’ p73âˆ’/âˆ’ mice are not viable.
We have therefore started a developmental study for this effect starting at E9.5. For investigating Mdm4 and p73
interaction in tumorigenesis, I am establishing a cohort of Mdm4Tg15
p73+/âˆ’ to study the tumorigenesis comparing to Mdm4Tg15
and p73+/âˆ’ mice.
Conclusion
This study will provide a comprehensive in vivo characterization of potential Mdm4 and p73 interactions both
in development and tumorigenesis. Since Mdm4 is overexpressed in many tumors and most tumors lack p73
mutations, this study may identify a novel mechanism for inactivation of p73 in human cancer.
Financial Disclosure (Mehrnoosh Tashakori)
No
FDA Disclosure
Cleared:Yes
Keywords
Mdm4
p73
Development
Tumorigenesis
Abstract ID: 225
Increased DNA Repair Capacities And P53/MDM2 Pathway Aberrations Hallmark Neuroblastoma Cell Lines With
The Alternative Lengthening Of Telomeres (ALT) Phenotype
Author List
1. Presenting Author: Ahsan Farooqi
2. Additional Author: Ashly Hindle
3. Additional Author: Balakrishna Koneru
4. Additional Author: Rachel Blaydes
5. Additional Author: Loretta Lau
7. Additional Author: Roger Reddel
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 01:25 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Neuroblastoma (NB) is a malignant pediatric tumor of the sympathetic nervous system. Approximately 10-20% of
neuroblastoma tumors maintain telomere length by activating a telomerase-independent alternative lengthening of
telomeres (ALT) mechanism, and that these tumors are associated with high-stage disease, and a poor prognosis.
Understanding the ALT phenotype in NB may inform strategies to improve outcome for high-risk NB.
Methods
mRNA expression of TERT (the catalytic component of telomerase) and TERC (RNA template) was measured by
RT-PCR, and telomerase activity (TA) by RQ-TRAP. The C-Circle (CC) telomere plasmid assay, telomere content (TC),
and MYCN gene copy number utilized PCR; p53 function was assessed by quantifying induction of p21 protein by flow
cytometry after irradiation. Expression profiling was carried out with custom-designed Taq-Man Low Density Arrays
(TLDAs) (ABI) that quantified expression of 62 DNA-repair genes in a panel of 12 NB cell lines, 4 ALT and 8
telomerase-positive. Of the telomerase-positive lines, 2 were drug-sensitive, 6 multi-drug resistant. Cell line identities were
confirmed using short tandem repeat (STR) genotyping. Response to cytotoxic drugs was assessed using DIMSCAN.
Results
From a panel of 40 human NB cell lines we identified 4 ALT NB lines, LA-N-6, SK-N-FI, CHLA-90, and COG-N-291,
that maintain telomere length with significantly low mRNA levels of TERT and TA (p<.05) relative to telomerase-positive
(TA+) NB cell lines. The four ALT lines had TC > 2-fold that of TA+ NB cell lines (p<.05), two of which demonstrated
telomere repeat C-circles, and all lacked MYCN genomic amplification. 3 out of the 4 ALT lines lacked p53 function;
LA-N-6, the sole p53-functional ALT line carries a homozygous deletion of p14arf. ALT lines had a significant increase
(p<.05) in the expression of 28 of the 62 DNA-repair genes analyzed by TLDA relative to telomerase-positive lines
(including those that manifest multidrug resistance); 10 of these genes are involved in the nucleotide excision repair
pathway. All 4 ALT cell lines showed a high degree of multi-drug resistance, with the mean concentration cytotoxic to
90% of the ALT cells (IC90) being higher than clinically achievable plasma levels for melphalan (1.5-fold), etoposide
(4-fold), topotecan (5-fold), and carboplatin (4-fold).
Conclusion
ALT-based telomere maintenance in NB cell lines was associated with loss of p53 function, increased expression of
DNA-repair genes, and resistance to DNA-damaging chemotherapy. ALT NB tumors may comprise an especially high-risk
subset of neuroblastoma. Novel, p53-independent therapies should be considered to treat NB tumors harboring the ALT
phenotype.
Financial Disclosure (Ahsan Farooqi)
No
FDA Disclosure
Cleared:Yes
Keywords
Neuroblastoma
Telomeres
Drug Resistance
DNA Repair
Abstract ID: 226
Silencing Of Farnesoid X Receptor In Human Colon Cancer By Epigenetic Mechanisms Is Associated With Cancer
Progression
Author List
1. Presenting Author: Ann Thomas
2. Additional Author: Le Zhan
3. Additional Author: Julie Izzo
4. Additional Author: Dipen Maru
5. Additional Author: Rebecca Slack
6. Additional Author: Jeffery Morris
7. Additional Author: Grace Guo
8. Additional Author: Garth Powis
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Colon cancer is the third leading cause of cancer related deaths in the United States. Epidemiological studies suggest an
increase in the intestinal bile-acid load resulting from the consumption of a high-fat diet is a significant risk factor for colon
cancer. Bile acids are the endogenous ligands for the farnesoid X receptor (FXR), a ligand-activated transcription factor
and member of the nuclear receptor superfamily, and high levels of bile acids can promote colon cancer development. FXR
is essential for maintaining bile-acid homeostasis by regulating bile-acid synthesis and transport, preventing the
accumulation of intestinal bile acid levels to cancer promoting levels. Previous results from our laboratory and others have
demonstrated that FXR knockout mice are more susceptible to the development of colon adenocarcinomas, indicating that
FXR plays a suppressive role in colon tumor formation. This study investigates the role of FXR in the development of
human colon cancer.
Methods
Immunohistochemistry (IHC) was used to label for FXR in normal human colon (n=47), colon polyps (n=30), and colon
adenocarcinomas staged I-IV (n=28, 34, 53, and 6). SYBR Green quantitative PCR (qPCR) was done to measure mRNA
levels of FXR and FXR target genes in normal human colon and colon cancers staged I-IV as well as colon cancer cell
lines. To test if FXR expression was suppressed by DNA methylation, colon cancer cell lines were treated with a DNA
methyltransferase (DNMT) inhibitor and DNMT siRNA and FXR mRNA measured by real-time qPCR.
Immunoprecipitation with an antibody against 5-methylcytosine (MeDIP) analysis was done in human colon cancer cell
lines to determine methylation of NR1H4 (gene encoding FXR) promoter.
Results
IHC and qPCR analysis reveals that the expression and function of FXR is markedly reduced early in colon cancer
progression, with suppression seen in precancerous lesions. Furthermore, results suggest DNA methylation as a mechanism
of FXR silencing in colon cancer and confirms methylation of the FXR promoter.
Conclusion
Our studies show that FXR is silenced in early in human colon cancer progression possibly by DNA methylation, which
could be a cancer promoting event. The overall mechanism of FXRâ€™s anti-tumorigenic activity is not fully established
but appears to be both dependent and independent of its ability to regulate bile acid levels. Restoration and enhancement of
FXR activity, by blocking DNA methylation or increasing baseline activity of FXR, represents a potential therapeutic
option for the treatment of colon cancer.
Financial Disclosure (Ann Thomas)
No
FDA Disclosure
Cleared:Yes
Keywords
farnesoid x receptor
colon cancer
DNA methylation
bile acids
Abstract ID: 227
HIT-enabled Cancer Clinical Trials
Author List
1. Additional Author: Rebecca Kush
2. Presenting Author: Landen Bain
3. Additional Author: Charles Geyer
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The execution of clinical research studies at healthcare sites is encumbered by processes that are duplicative and expensive.
Now that healthcare information technology (HIT) is becoming more pervasive, there are opportunities to leverage such
technologies to improve research-related work processes. For example, research data capture often requires manual
transcription of data from an electronic health record (EHR) into an electronic data capture (EDC) system provided by the
research sponsor. The same EHR data are then printed and stored as source documents for the study. Direct transfer of
data from the EHR into an EDC would eliminate transcription errors and substantially reduce personnel and auditing costs.
To be effective, a solution must be standards-based so that all EHRs and research systems can participate, and researchers
can implement streamlined processes regardless of the EHR system installed at their research site. This abstract describes
a proposed methodological investigation of HIT-enabled Cancer Clinical Trials for Clinical Development which uses a
standards-based solution drawing on CDISC, HL7 and IHE specifications.
Methods
The project will identify a research protocol through the statewide Clinical Trials Netork of Texas (CTNeT), and recruit
sites with EHRs to participate in a test bed for a standards-based solution. The HIT-enabled study will seek to improve
work processes at multiple sites that use various EHR systems. Work measurement studies will document current
processes. New processes will be designed based on Healthcare Link, the standards-based solution developed by CDISC.
The study team will engage with NCI, ONC and FDA to obtain their input on the process redesign and endorse the novel
approach as appropriate. Following initial systems testing using IHE's Connectathon and Projectathon methods, the
solution will be implemented at participating sites to conduct a research trial that meets regulatory requirements. After an
implementation period, a second work measurement will be done to compare the new processes to the old.
Results
The study will assess the improvement in efficiency and business value of HIT-enabled research. Ultimately, this study
seeks to demonstrate the utility of the concept and accelerate the rate of adoption.
Conclusion
The CDISC Healthcare Link solution has been through a rigorous, multi-year process of development, testing,
demonstration and single-site implementations. The time is right to expand the adoption of HIT-enabled research beyond
the single site, single EHR implementations to date. This methodological study will demonstrate efficiency, identify gaps
and promote adoption to accelerate cancer research opportunities.
Financial Disclosure (Landen Bain)
No
FDA Disclosure
Cleared:Yes
Keywords
HIT
Healthcare Link
EHR
Standards
Abstract ID: 228
Expert-Guided Text Classification
Author List
1. Presenting Author: Erel Joffe
2. Additional Author: Jorge Herskovic
3. Additional Author: Charles Bearden
4. Additional Author: Elmer Bernstam
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Presentation1.jpg
Summary
Introduction
Automatically identifying notes pertaining to specific phenotypes in medical records can be useful for a variety of tasks.
Current natural language processing (NLP) approaches generally rely on identifying similarities between labeled notes
(e.g., breast cancer yes/no). We hypothesized that identifying relevant sections of clinical text (as opposed to entire note or
record), would improve the performance of NLP classifiers.
Methods
A single physician reviewed 1027 clinical notes from 50 breast cancer patientsâ€™ records, and highlighted text relevant
to labeling a record as positive for breast cancer. Based on notes from the first 25 patients we created two datasets
(highlights and control). For the control dataset, notes containing highlighted text were labeled as positive for breast
cancer, and notes without highlighting were labeled as negative. For the highlights dataset, we extracted highlighted
sections into separate notes and labeled these as positive. The remainder of the note and notes without highlighting were
labeled as negative. We created a validation set from notes of the remaining 25 patients labeled as positive or negative on
the note level. We used the Automated Retrieval Console (ARC) to extract text features from the notes, and build
classifiers for identifying positive notes. We set ARC to generate classifiers for each feature, and calculated precision (P),
recall (R) and F measure (F) using a 3 fold cross validation. We then generated two feature sets by choosing for each
dataset the five features with the highest precision. We used these feature sets in training classifiers on the highlights and
control datasets. We evaluated the classifiers' performance against the validation set. We also evaluated two classifiers
generated automatically by ARC.
Results
The three classifiers built on the highlights dataset had a P=0.98, R=0.29, F=0.45, P=0.98, R=0.34, F=0.50 and P=0.98,
R=0.18, F=0.30. The three classifiers built on the control dataset had a P=0.75, R=0. 99, F=0.85, P=0.78, R=0.99, F=0.87,
and P=0.78, R=0.95, F=0.86.
Conclusion
Classifiers based on highlighted sections had a higher precision but lower recall for identifying notes associated with
disease status. These finding were consistent across multiple features. While the loss of recall in our method was
considerable, high precision is a core requirement in many medical applications. A limitation of this study is that it
evaluated only notes of patients with breast cancer. In summary, identifying key sections that are relevant for the labeling
of a note can improve the precision of generated classifiers.
Financial Disclosure (Erel Joffe)
No
FDA Disclosure
Cleared:Yes
Keywords
Natural language processing
Expert knowledge acquitision
Phenotyping
None
Abstract ID: 229
Targeting Neuroblasts And Neuroblast-Supportive Macrophages With Dual-Specific NKT Cells
Author List
1. Additional Author: Andras Heczey
2. Additional Author: Daofeng Liu
3. Additional Author: Ekaterina Marinova
4. Additional Author: Jie Wei
5. Additional Author: Amy Courtney
6. Additional Author: Eric Yvon
7. Additional Author: Gengwen Tian
9. Presenting Author: Leonid Metelitsa
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
Introduction
The infiltration of primary tumors with Valpha24-invariant Natural Killer T (NKT) cells is associated with good outcome
in neuroblastoma and other types of cancer. Mechanistic studies revealed that instead of attacking tumor cells directly,
NKT cells target CD1d-positive tumor-associated macrophages (TAMs). However, effective immune control of tumor may
also require direct and specific attack against the tumor cells.
Methods
We genetically modified ex vivo propagated human NKT cells using a retroviral vector encoding a chimeric antigen
receptor (CAR) that targets GD2 ganglioside which is highly expressed by neuroblastoma cells and represents a clinically
validated therapeutic target. The functional activity of the native TCR and CAR.GD2 in the gene-modified NKT cells was
tested using CD1d+ TAMs and GD2+ neuroblastoma cells, respectively. Next, we encoded co-stimulatory endodomains in
cis with the CAR.GD2 (CD28, CD134, CD137 and their combinations) to enable optimal CAR-mediated signaling for
NKT cell cytotoxicity, cytokine production, proliferation, and survival.
Results
Expression of CAR.GD2 constructs rendered NKT cells highly cytotoxic against GD2-positive neuroblastoma cells while
leaving their native CD1d-restricted cytotoxicity unaffected. Only the CAR.GD2 NKT cells that expressed the
co-stimulatory endodomains from CD28, CD134, and/or CD137 underwent rapid proliferation upon specific stimulation
sufficient to enable clinical scale expansion of the gene-modified NKT cells. While adoptive transfer of the parental NKT
cells only transiently suppressed growth of metastatic neuroblastoma in humanized NOD/SCID/IL-2Î³(null) mice, NKT
cells expressing CAR.GD2 with CD28 or CD137 endodomains had potent and long-lasting anti-metastatic activity.
Furthermore, we discovered a striking and previously unanticipated Th2-like (IL-4 and IL-10) and Th1-like (IFNÎ³ and
GM-CSF) polarization of NKT cells expressing CAR.GD2/CD28 and CAR.GD2/CD137, respectively.
Conclusion
NKT cells engineered to express CAR.GD2 with co-stimulatory endodomains can be expanded to clinical scale, target both
neuroblasts and neuroblast-supportive TAMs, and have potent anti-tumor activity. In addition to directing NKT cell
cytotoxicity toward tumor cells, CAR constructs that contain CD137 co-stimulatory endodomain can program NKT cells to
produce large amounts of IFNÎ³ and GM-CSF that in turn activate multiple types of anti-tumor effector cells. These results
establish the potential of NKT cells to serve as a novel platform for anti-tumor CAR therapy in neuroblastoma and other
types of cancer.
Financial Disclosure (Leonid Metelitsa)
No
FDA Disclosure
Cleared:Yes
Keywords
chimeric antigen receptor (CAR)
neuroblastoma
adoptive immunotherapy
Natural Killer T (NKT) cells
Abstract ID: 230
A Systems Biology Approach Reveals Common Metastatic Pathways In Osteosarcoma
Author List
1. Presenting Author: Ricardo Flores
2. Additional Author: Ching Lau
3. Additional Author: Serrine Lau
4. Additional Author: Marina Vannucci
5. Additional Author: Tsz-Kwong Man
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
 
Osteosarcoma (OS) is the most common malignant bone tumor in pediatrics. The survival rate of patients with metastatic
disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis will not likely
identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic
pathways that are jointly supported by both mRNA and protein levels in two distinct human metastatic OS models. 
Methods
 
The human metastatic OS models used consist of a pair of isogenic OS cell lines (low metastatic parental cell line and
highly metastatic subline), namely HOS/143B and SaOS-2/LM7. We obtained mRNA expression data by microarray
analysis, and captured a specific subset of N-linked glycoproteins by lectin affinity chromatography. Subsequently, we
identified the glycoproteins by mass spectrometry and quantified by spectral counting method. The genomic and
glycoproteomic data were integrated by the topological analysis, and results were validated by Western blotting and
reverse phase protein arrays (RPPR). 
Results
 
Pathway analysis of the up-regulated genes and glycoproteins separately revealed pathways associated to metastasis
including RAS-related G-proteins signaling, cell cycle regulation, and epithelial-to-mesenchymal-transition. Nonetheless,
no common significant pathway was found between the two metastatic models. To address this issue, we used a topological
analysis based on a â€œshortest pathâ€• algorithm to identify topological nodes that remained hidden from the
transcriptomic and glycoproteomic analyses. Analysis of the significant topological nodes identified important common
pathways, including â€œCytoskeleton remodeling/TGF/WNTâ€•, â€œDevelopment/WNT signalingâ€•, and â€œCell
adhesion/Chemokines and adhesionâ€•. Of these, the â€œCytoskeleton remodeling/TGF/WNTâ€• was the top ranked
common pathway, and up-regulation of proteins within this pathway was validated using RPPR. The next step is to
determine if we can utilize the candidates identified by the systems biology approach as circulating prognostic biomarkers.
We will use Multiple Reaction Monitoring or Luminex bead assays to quantify a set of selected candidates in the plasma
samples from a cohort of OS patients. The correlations of the candidate biomarkers with tumor progression, metastases,
and patient survival will then be determined. 
Conclusion
 
In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common
metastatic mechanisms in OS. Since WNT signaling and chemokines have been previously implicated in OS and other
tumors, further characterization and validation in human samples of these common pathways may lead to novel prognostic
biomarkers and therapeutic strategies for curing metastatic OS. 
Financial Disclosure (Ricardo Flores)
No
FDA Disclosure
Cleared:Yes
Keywords
Ostoesarcoma
Metastasis
Systems biology
Topological analysis
Abstract ID: 231
Deletion of Estrogen Receptor Beta DNA Binding Domain Does Not Alter The Receptor''s Functions In The Mouse
Ventral Prostate
Author List
1. Presenting Author: Laure Maneix
2. Additional Author: Per Antonson
3. Additional Author: Sabrina Rochel-Maia
4. Additional Author: Hyun-Jin Kim
5. Additional Author: Margaret Warner
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
 
The anti-proliferative properties of estrogen receptor Î² (ERÎ²) and its ability to regulate growth and differentiation of the
prostate epithelium make it interesting as a therapeutic target in prostate cancer. The first ERÎ²-/- mouse was
created by inserting a neocassette into the ERÎ² gene to interrupt the gene at the DNA binding domain (DBD). In this
original knockout, aging ERÎ²-/- mice develop prostate hyperplasia and upon estradiol treatment, they also
develop prostatic intraepithelial neoplasia lesions, which are believed to be premalignant. These mice were also
characterized by a reduction in the ability to ovulate and disruption of neuronal migration during fetal development. In
2008, another ERÎ² mutant mouse was generated by inserting LoxP sites around exon 3. This exon 3-deleted mouse was
infertile, due to the inability of the female mice to ovulate but did not present any other defects in the prostate or the brain.
Because of lack of abnormalities in this new knockout mouse, the phenotype of the original ERÎ²-/- mouse
deemed to be due to the presence of the neocassette which remained in the gene.
Methods
In the present study, a new ERÎ² knockout mouse was generated by inserting Lox P sites around the third exon which
encodes the second zinc finger in the DBD of the receptor. Exon 3 was then deleted by crossing this mouse with a
CMV-Cre or a Rosa-Cre deleter mouse.
Results
 
The only abnormality found in the new mutant ERÎ² mouse was the inability of the female mice to ovulate. We
demonstrated that although a stop codon should have prevented translation of the protein after exon 2, these mice produce
an ERÎ² protein in which the second zinc finger is missing. This protein was detected in the nuclei of prostate epithelial
cells in a speckled pattern. mRNAs extracted from the ERÎ²-/- prostates were also translated in vitro
and produced a protein of approximately 50 kDa. Moreover, DNA binding of prostate nuclear extracts from these
mice to EREs and AP-1 responsive elements was inhibited by ERÎ²-specific antibodies. In contrast to the original knockout
mouse, the expression of Ki67, androgen receptor and PKC-zeta by the prostate epithelial cells was not modified in the
new ERÎ²-/- mouse.
Conclusion
 
We conclude that most of the functions of ERÎ² remain intact in the prostate when its DBD is disrupted and that ERÎ²
control of prostatic growth is probably mediated through the interaction of ERÎ² with other transcription factors like
AP-1.
Financial Disclosure (Laure Maneix)
No
FDA Disclosure
Cleared:Yes
Keywords
Estrogen receptor beta
Prostate cancer
Knockout mouse
Ventral prostate
Abstract ID: 232
Collaboration Of AR And ERÎ± In Hormone Resistance And Estrogen Action
Author List
1. Presenting Author: Yassine Rechoum
2. Additional Author: Domenico Iacopetta
3. Additional Author: Ines Barone
4. Additional Author: Sebastiano AndÃ²
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Aromatase inhibitors (AIs) have emerged as the therapy of choice for the treatment of estrogen receptor alpha
(ERÎ±)-positive breast cancer, although many patients will eventually develop resistance to this treatment. The
involvement of residual ERÎ± function in AI resistance is established, but the role of the androgen receptor (AR) is not
known. It has been estimated that about 70%-80% of ERÎ±-positive breast cancer co-express the AR, but that AR agonists
can either inhibit or stimulate breast cancer cell proliferation. Thus it is important to determine if there are clinically useful
biomarkers predicting ARâ€™s effects in breast tumors. We have previously shown a role for AR overexpression in
tamoxifen resistance in ERÎ±-positive MCF-7 breast cancer cells; here we hypothesized that AR overexpression might
similarly be involved in resistance to the AI anastrazole (Anas).
Methods
MCF-7 cells were transfected to express the aromatase gene (MCF-7 Arom), or the aromatase and AR (MCF-7 AR Arom
cells). Aromatase and AR expression levels were evaluated by western blot analysis. Proliferation was measured using
anchorage-independent soft agar and MTT assays in the presence of the androgen substrate androstenedione (AD), or AD
plus Anas. Specific antagonists for ERÎ± (ICI 182,780) or AR (MDV3100 and Bicalutamide) were also used. ERÎ± and AR
transcriptional activities were measured using ERE-luciferase reporter assays. Localization of ERÎ± and AR was visualized
using confocal microscopy and proximity ligation assay (PLA).
Results
Anas inhibited AD-stimulated growth in MCF-7 Arom cells, however AR Arom-expressing cells were resistant to growth
inhibition by Anas. Similarly, Anas did not inhibit ERÎ± transcriptional activity in AR Arom cells. Enhanced activation of
pIGF-1R, pIRS-1, pAKT, and pMAPK were also observed in AR Arom cells, suggesting constitutive activation of
nongenomic signaling in these cells. Consistent with activation of these potential treatment â€œescapeâ€• mechanisms,
inhibitors to AKT and IGF-1R restored sensitivity to Anas. Sensitivity to Anas was also restored using the AR antagonist
MDV3100. These results suggest that both AR and ERÎ± must be targeted, and blocked to restore sensitivity to hormonal
therapies when AR is overexpressed in ERÎ±-positive breast cancer cells. Unexpectedly, AR contributed to ERÎ±
transcriptional activity in AR aromatase expressing cells which could be blocked with the AR antagonist bicalutamide.
Accordingly, we discovered that AR and ERÎ± co-localized both in the cytoplasm, and in the nucleus of AD+Anas-treated
cells, suggesting potential activation of both non-genomic and nuclear-mediated effects when AR is overexpressed in
ERÎ±-positive cells.
Conclusion
Using a model of ERÎ±-positive breast cancer cells expressing exogenous aromatase and AR, we have demonstrated that
AR overexpression confers resistance to the AI Anas. These results suggest that it will be necessary to target both AR and
ER in patients whose tumors express elevated levels of AR. In addition, inhibitors to the AKT/IGF-1R signaling pathways
may also provide alternative approaches to restore hormone sensitivity.
Financial Disclosure (Yassine Rechoum)
No
FDA Disclosure
Cleared:Yes
Keywords
Androgen receptor
ERa
aromatase inhibitors
resistance
Abstract ID: 234
An Injectable, Immune Priming Center For Cancer Vaccines: Simultaneous, Single-Carrier Delivery Of
Tumor-Antigens And Immune-Modulatory Nucleic Acids To Dendritic Cells
Author List
1. Presenting Author: Eileen Dawson
2. Additional Author: Jardin Leleux
3. Additional Author: Pallab Pradhan
4. Additional Author: Hong Qin
5. Additional Author: Larry Kwak
7. Additional Author: Krishnendu Roy
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
CPRIT_Figures.jpg
Summary
N/A
Introduction
Despite different immunological strategies, development of a clinical therapeutic cancer vaccine has proven elusive. This
research focuses on developing novel formulations that allow simultaneous delivery of protein/peptide-based tumor
antigens and immune-modulatory nucleic acids (siRNA and immune stimulatory CpG) to the dendritic cells (DCs) in-vivo.
Such formulations allow a synthetic immune-priming center to be created at the site of immunization and simultaneously
deliver the tumor antigen to DCs and modulate their immune response. The hypothesis is that using such a DC-targeted
combinatorial delivery system we will be able to elicit strong Th1 and Cytotoxic T Lymphocyte (CTL) response in vivo.
This can become a platform technology where the biomolecules (antigen and immunomodulatory agents) can be easily
varied based on particular cancers.
Methods
Poly(lactide-co-glycolide) (PLGA) microparticles and nanoparticles were prepared using a water/oil/water emulsion and
surface functionalized with polyethylenimine to generate cationic particles that were characterized for size and zeta
potential. Ovalbumin (OVA) or pDNA antigen and/or with multiple toll-like receptor ligands (IL10 siRNA and 1826 CpG)
was loaded onto the surface of the particles by electrostatic interaction. Murine bone marrow derived dendritic cells
(BMDCs) were used for activation studies. In vivo studies were conducted by injecting various formulations of the
microparticles in combination with hydrogel. Mice were vaccinated 3 times before being challenged with A20 lymphoma
or B16 melanoma cells. Tumor free survival was followed thereafter.
Results
Both micro and nanoparticles have been successfully surface loaded with different levels of nucleic acids and antigen on
the same particle (summarized in Table 1). BMDCs (Figures 1 and 2) showed high expression of activation markers.
Preliminary in vivo immunization studies with PLGA-MP-hydrogel system showed promising results in tumor models.
90% mice of PLGA microparticles co surface loaded with pDNA, CpG and Poly IC group were tumor free as compared to
40% mice injected with naked pDNA after 16 days of A20 lethal tumor challenge. PLGA MP co surface loaded with
pDNA and IL10siRNA on one particle and CpG on separate particle did relatively well with 60% mice tumor free at 16
days post challenge.
Conclusion
A delivery system capable of delivering both surface loaded antigens as well as immune-modulatory nucleotides was
developed. We were able to efficiently adsorb our antigens and adjuvants. This combined with our DC stimulation data
indicates that we have created molecules capable of activating DCs. Preliminary in vivo immunization studies with PLGA
microparticle-hydrogel systems have shown promising results.
Financial Disclosure (Eileen Dawson)
No
FDA Disclosure
Cleared:Yes
Keywords
Cancer Vaccine
siRNA
Microparticle
Nanoparticle
Abstract ID: 235
Chimeric T Cells For Therapy Of Hodgkin Lymphomas (HL) And CD30+ Non Hodgkin Lymphomas (NHL)
Author List
1. Presenting Author: Barbara Savoldo
3. Additional Author: Enli Liu
4. Additional Author: Zhuyong Mei
5. Additional Author: Hao Liu
6. Additional Author: Bambi Grilley
8. Additional Author: Adrian Gee
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Front-line therapies carry significant long-term toxicity in patients with HL, and few curative options are available for
patients with refractory HL. Thus, novel therapies are needed. CD30 molecule, invariably expressed by malignant HL cells
both at diagnosis and relapse is a recognized target antigen for this disease. CD30-specific MAbs have an encouraging
response rate; however passive immunotherapy is characterized by transient effects and limited tissue bio-distribution. We
have thus hypothesized that the antitumor effects obtained by targeting the CD30 molecule can be further augmented and
sustained by engineering T-cells to express a CD30-specific chimeric antigen receptor (CAR). We have therefore initiated
at our institution a clinical trial to assess safety and efficacy of this novel immunotherapy-based approach in heavily
pretreated patients with CD30+ HL or NHL.
Methods
T-cell products were generated with immobilized anti-CD3 and anti-CD28 MAbs, transduced with a retroviral vector
encoding the CAR.CD30 containing the CD28 costimulatory endodomain and then expanded in IL-2. T-cell lines are
characterized for transduction efficiency, composition of memory vs effector cells and functionally. Eligible patients are
enrolled in a phase-I dose-escalation study, consisting of three dose levels. Monitoring of patients consists of history,
physical examination and routine laboratory investigations at different time-points. The persistence of CAR+ T cells is
monitored by a specific Q-PCR assay designed to detect the retroviral integrants. Clinical evaluation for antitumor effects
is performed 6 weeks post-infusion.
Results
We have manufactured T-cell lines for 4 patients. Starting from 15x106 PBMCs, we obtained 380x10e6 +/- 68x10e6
CAR+ T cells in 13+/-4 days of culture. The transduction efficiency is 89%+/-1%. Phenotypic analysis shows that
68%+/-18% of the cells are CD8+ T cells, with a majority of them being effector T cells [CD45RO+ = 98% +/-1%,
CD62L+ = 12%+/-5%). Cytotoxicity assay based on 51Cr-release assay confirms that CAR+ T-ells lyze CD30+ tumors
(62%+/-9% at 20:1 E:T ratio) with negligible effects on CD30 negative targets (4%+/-2%). So far, one patient with
relapsed HL has received CAR+ T-cells at the first dose level (2x10e7/m2). After infusion, no adverse events occurred.
The patient has stable disease at the 6 weeks follow-up. Molecular signals for CAR.CD30 increased post-infusion, peaking
at the 2 weeks follow-up.
Conclusion
The generation of functional CAR+ T-cells seems feasible in the patients so far enrolled. We will continue the study to
assess the safety of T-cell infusions and to evaluate patients for evidences of clinical benefits.
Financial Disclosure (Barbara Savoldo)
No
FDA Disclosure
Cleared:Yes
Keywords
Hodgkin Lymphoma
Immunotherapy
Chimeric antigen Receptor
Gene therapy
Abstract ID: 236
Engineering A Human Methionine-Degrading Enzyme For Systemic Depletion Therapy Of CNS Tumors
Author List
1. Presenting Author: Olga Paley
3. Additional Author: Wei-Cheng Lu
4. Additional Author: Jian Hu
5. Additional Author: Nai-Kong Cheung
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
CPRIT Olga Paley Graphic.jpg
Summary
Introduction
Many cancers exhibit significant metabolic deviations from normal cells including a higher demand for particular amino
acids. Some, such as glioblastomas, medulloblastomas, and neuroblastomas have shown a marked sensitivity to
L-Methionine (L-Met) depletion. In contrast, normal cells have the ability to tolerate the absence of L-Met and recover
fully upon its resupply. Nutritional deprivation alone has been insufficient to achieve the therapeutically relevant
concentrations of L-Met in serum which has led to the investigation of the Pseudomonas putida enzyme
methionine-gamma-lyase (MGL) as a therapeutic for systemic L-Met depletion. Administration of MGL dramatically
decreased the serum L-Met pool and inhibited growth of human tumors xenografted in mice. However, the bacterial
enzyme was highly immunogenic in primates- a drawback exacerbated by its short half-life in serum (t1/2 =1.9 Â±0.2 hr)
and consequent requirement for more frequent dosage. Since the human genome does not encode a human MGL enzyme,
we created a methionine degrading enzyme by reengineering the structurally homologous human
cystathionine-gamma-lyase (hCGL) for de novo methionine-lyase activity.
Methods
We used rational design and scanning saturation mutagenesis to generate libraries of clones which were subjected to a
novel high throughput screen for methionine-lyase activity.
Results
Through these efforts, we identified a variant of hCGL with three amino acid substitutions (hCGL-NLV) that displays
therapeutically relevant rates of L-Met degradation, a dramatically increased half-life compared to the bacterial enzyme,
and indistinguishable cytotoxicity towards 14 neuroblastoma cell lines from that of the P. putida MGL.
Intravenous administration of PEGylated hCGL-NLV in mice reduced serum L-Met from 123 ÂµM to <5 ÂµM for over
30 hours. Importantly, treatment of neuroblastoma mouse xenografts with PEGylated hCGL-NLV resulted in near
complete cessation of tumor growth. This variant was further used as a scaffold for additional engineering. We have now
identified a novel variant with a total of seven mutations that shows a four-fold improvement in kinetics
(kcat/KM ) over hCGL-NLV and an improved in vitro cytotoxicity profile.
Conclusion
The engineered enzymes are dramatically more stable in serum than the bacterial MGL. Additionally, due to the human
origin of the engineered enzyme, we expect to circumvent the adverse immune responses observed in previous primate
studies, including neutralizing antibodies and anaphylactic reactions. Since the mode of action of this therapeutic is
systemic and does not require breaching the blood-brain barrier, this enzyme may be particularly attractive for applications
against sensitive tumors that arise from or metastasize to the central nervous system.
Financial Disclosure (Olga Paley)
No
FDA Disclosure
Cleared:Yes
Keywords
protein engineering
central nervous system (CNS) cancer
methionine depletion
biotherapeutics
Abstract ID: 237
miRNAs Sensitize Lung Carcinoma Cells To Erlotinib In Vitro
Author List
1. Presenting Author: Jane Zhao
2. Additional Author: Kevin Kelnar
3. Additional Author: Sarah Dysart
4. Additional Author: Chris Daige
5. Additional Author: Jason Wiggins
6. Additional Author: Michael Omotola
7. Additional Author: Leslie Priddy
8. Additional Author: Terri Muenzer
9. Additional Author: Neil Leatherbury
10. Additional Author: David Brown
11. Additional Author: Jay Stoudemire
12. Additional Author: Paul Lammers
13. Additional Author: Andreas Bader
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Current treatment options for lung cancer are limited and insufficient. Erlotinib (marketed as Tarcevaâ„¢), a small
molecule inhibiting the epidermal growth factor kinase receptor (EGFR), is an FDA-approved drug for patients with
non-small cell lung cancer (NSCLC) after failure of prior conventional chemotherapy. The therapy extends overall patient
survival by only ~2 months, due to primary or acquired secondary resistance. Thus, novel therapies are needed that - alone
or in combination - improve patient outcome. Mirna Therapeutics, Inc., is developing cancer therapeutics based on tumor
suppressor microRNAs (miRNAs), a class of natural, non-coding RNAs that function as master regulators by modulating
the expression of tens to hundreds of genes and by controlling several cellular pathways at once. Certain miRNAs are
frequently deregulated in cancer cells and, consequently, so are pathways downstream. Replacing tumor suppressor
miRNAs via â€œmiRNA Replacement Therapyâ€• has proven to effectively eliminate tumor growth and prolong survival
in animal models of cancer. The molecular mechanisms of miRNA-mediated tumor suppression suggest that these
miRNAs can sensitize cancer cells to Erlotinib.
Methods
 
Lung carcinoma cell lines were used in the combination study. They included cell lines resistant (H1299, H460, HCC827
resistant) or sensitive (HCC827 parental) to Erlotinib. The main aim of the combination was to achieve an enhanced
therapeutic effect of erlotinib (decreased IC50) and reduce the dose and toxicity of Erlotinib. The evaluation of
combinatorial work was performed following the â€œFixed Concentration Modelâ€•. The cytotoxic compound A
(Erlotinib) is tested at 7-8 concentrations, and compound B (miRNA) at one weak concentration. Drug or miRNA effects
on cellular proliferation were assessed using AlamarBlue assay. IC50 values of erlotinib alone and in the combinations
were calculated using the GraphPad software.
Results
HCC827 resistant cells were generated by treating the parental cells at low concentration of Erlotinib (IC10), and
continually increasing the concentration upto IC90 over 2-3 months resulting in an HCC827 resistant cell line. We
evaluated various Erlotinib/miRNA combinations using the miRNA at ~IC25 and erlotinib at increasing concentrations in
each cell line. We identified 5 miRNAs that sensitize various resistant and sensitive NSCLC cells by 4 to 100-fold. 
 
Conclusion
We have identified 5 miRNAs that sensitize cancer cells to erlotinib in vitro. The trend of IC50 fold reduction among the
Mirnaâ€™s miRNAs was similar cross all the tested lung cancer cell lines. The combinatorial effect will be further
evaluated in vivo lung cancer model. 
 
Financial Disclosure (Jane Zhao)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 238
Zero Tolerance For Cancer Pain
Author List
1. Presenting Author: Howard Gutstein
2. Additional Author: Bing Mo
3. Additional Author: Shanping Shi
4. Additional Author: Katherine Barker
Oral Sessions
Oral Sessions
Status
Rejected
November 15, 2011 @ 01:00 AM
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Wang et al. Fig 4.jpeg
Summary
Introduction
For centuries, opioid drugs such as morphine have been the first-line treatment for severe cancer pain. However, over time
tolerance to opioid analgesia develops, leaving few treatment options and leading to tremendous suffering for cancer
patients. Two main hypotheses have been proposed to explain opioid tolerance: that analgesic signalling decreases due to
opioid receptor desensitization and internalization; and that a sustained opioid-mediated signal causes tolerance. However,
there is experimental and clinical evidence contradicting both theories. Here we suggest a novel hypothesis by showing that
platelet-derived growth factor beta (PDGFR-Î²)-mediated signalling is necessary and sufficient to cause morphine
tolerance.
Methods
All protocols were approved by our Institutional Animal Care and Use Committee. Drugs were administered to rats by the
intrathecal and subcutaneous routes. All drugs were administered in a vehicle that enabled imatinib to penetrate the
blood-brain barrier. Analgesia was assessed by tail flick or paw withdrawal latency. Rat C6 glioma cells were stimulated
either with morphine, fentanyl, naloxone, imatinib, or various combinations for 10 minutes to one hour. After treatment,
cells were harvested and prepared for immunopreciptiation and immunoblotting (IP/IB). Spinal cords were sliced into 2mm
segments and the substantia gelatinosa microdissected by transillumination. Tissues were also prepared for IP/IB.
Correction for IP efficiency was performed either by stripping the blots or splitting immunoprecipitates. All data were
expressed as a percentage of the vehicle groups. P < 0.05 was required for statistical significance.
Results
We found that morphine activated PDGFR-Î² in vitro and in vivo. Behavioral studies showed that the clinically used
PDGFR inhibitor imatinib completely eliminated and reversed morphine tolerance. If imatinib was subsequently
discontinued, animals reverted to the tolerant state. Also, administration of the PDGFR-Î² agonist platelet-derived growth
factor BB (PDGF-BB) rendered animals tolerant to subsequent morphine doses. Neither imatinib nor PDGF-BB affected
tolerance development to the analgesic drug clonidine, an Î±-2 adrenoreceptor agonist, suggesting that tolerance
modulation by PDGFR-Î² was opioid-specific.
Conclusion
Our results identify a specific cellular signal that selectively mediates morphine tolerance. This suggests that receptor
desensitization and internalization might are not the primary mediators of tolerance; rather, they impact tolerance by
modulating the effect of agonist-induced PDGFR-Î² signalling. Imatinib is widely used to treat leukemia and
gastrointestinal tumors, and clinically well-tolerated. This suggests that our findings could be rapidly translated into
clinical practice, potentially reducing the tremendous suffering endured by patients with cancer pain.
Financial Disclosure (Howard Gutstein)
No
FDA Disclosure
Cleared:Yes
Keywords
pain
tolerance
cancer
suffering
Abstract ID: 239
Improving The Preoperative Diagnosis And Management Of Thyroid Cancer Patients In Texas: Interim Results Of
A Multisite Prospective Molecular Study
Author List
1. Presenting Author: Sylvie Beaudenon-Huibregtse
2. Additional Author: Rupali Shinde
3. Additional Author: Laura Langfield
4. Additional Author: Jon Kemppainen
5. Additional Author: Dennis Wyllie
6. Additional Author: Emmanuel Labourier
7. Additional Author: Bernard Andruss
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cytological examination of fine needle aspiration (FNA) biopsies is the standard preoperative diagnostic tool to detect
thyroid malignancies and identify patients requiring surgery. However, FNA diagnosis remains inconclusive in 20 to 40%
of cases, leading to a large number of unnecessary surgeries. Research studies have shown that analysis of specific genetic
alterations can significantly improve the accuracy of thyroid cancer diagnosis. Molecular testing is now formally
recommended by the American Thyroid Association (ATA). To aid in resolving indeterminate preoperative FNA cytology,
we developed and launched the miRInformTM Thyroid Panel, a molecular testing service perform in Asuragenâ€™s CLIA
lab. Here we present an interim analysis of the first prospective, blinded, multisite clinical validation study design to assess
the clinical utility of miRInformTM Thyroid and its potential benefit for thyroid cancer patients.
Methods
Thyroid FNAs were collected in RNARetainÂ®, a single-use non-toxic solution for the preservation and stabilization of
intracellular nucleic acids at room temperature. DNA/RNA extraction and molecular evaluation were performed in
Asuragenâ€™s CLIA lab using the miRInformTM Thyroid Panel (BRAF, KRAS, NRAS and HRAS mutations, RET-PTC
and PAX8-PPARÎ³ translocations). FNA specimens with blinded cytological results were collected from 5 independent US
sites, including two sites located in Texas, The Austin Diagnostic Clinic (Dr. Moore) and Texas Diabetes & Endocrinology
(Dr. Blevins).
Results
A total of 522 specimens with known cytological diagnosis were tested, 376 benign, 88 indeterminate, 21 malignant and 37
non-diagnostic. Mutations were identified in 61 specimens (11.6%). Mutations in the RAS genes were the most common
(5.5%), followed by BRAF V600E (4.2%) and PAX8-PPARÎ³ translocations (1.9%). Collection of outcome data is
ongoing and correlation with cytological and molecular diagnosis will be presented. Interim analysis showed that
molecular testing can identify thyroid cancer missed by cytology with potential added benefits for patients such as
prediction of radioactive iodine treatment response.
Conclusion
Preoperative molecular evaluation of thyroid FNA exemplifies the goals set by CPRIT in the 2012 Texas Cancer Plan to
develop and implement screening and early detection methods, increase timely access to quality cancer diagnostic, support
the highest quality and most innovative research, and improve patient care by accelerating the movement of diagnostics
into practice. Additional characterization studies using next generation sequencing and microRNA expression profiling
could help identify novel biomarkers, increase the clinical sensitivity and accuracy of molecular testing, and further
improve the diagnosis and management of thyroid cancer patients in Texas.
Financial Disclosure (Sylvie Beaudenon-Huibregtse)
material? Yes
- Asuragen, Inc., Austin, Texas
FDA Disclosure
Cleared:Yes
Keywords
Prospective molecular study
Diagnostic molecular assay
Fine needle aspiration biopsies
Thyroid cancer patients management
Abstract ID: 240
test shannon
Author List
1. Presenting Author: Moonsup Lee
2. Additional Author: ASDFASDF Morton
Oral Sessions
None
Status
None
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Utinam meliore habemus ne mei. At adhuc erroribus sit, per utroque fierent id. Et eos ignota sanctus corrumpit. Debet
tibique perpetua an vim, wisi noster deseruisse in vis. Per at laudem facilisis, graeco diceret eos in, est mollis delectus
aliquando ex. Id pri vide inermis neglegentur. Choro homero appetere has ex, ex est graecis invenire. • Te iracundia
delicatissimi usu, et his accusamus hendrerit. Agam invenire te ius. Eripuit verterem theophrastus his eu, sed id quem
noster pericula, cum dolore nominavi eleifend et. Te sed sale sanctus volutpat. Ei dicat nemore reformidans vim, ex oblique
theophrastus mel. • Qui ea atqui causae pertinax, mea soluta dissentiet no. Dicam nostrud indoctum ea vel, ad has
aliquam menandri vulputate. In agam malis molestie vis, magna nullam audiam ut quo, legendos laboramus assueverit at
est. Ad quas munere persecuti his. Augue iudico nemore his no. Nam et possit virtute. Nam ocurreret intellegam id, no hinc
aliquid epicurei eum. Quo alii expetenda expetendis in. At eos graeci equidem. Eam ea tamquam incorrupte, cum cu iudico
impedit adipiscing. Utinam meliore habemus ne mei. At adhuc erroribus sit, per utroque fierent id. Et eos ignota sanctus
corrumpit. Debet tibique perpetua an vim, wisi noster deseruisse in vis. Per at laudem facilisis, graeco diceret eos in, est
mollis delectus aliquando ex. Id pri vide inermis neglegentur. Choro homero appetere has ex, ex est graecis invenire. 1. Te
iracundia delicatissimi usu, et his accusamus hendrerit. Agam invenire te ius. Eripuit verterem theophrastus his eu, sed id
quem noster pericula, cum dolore nominavi eleifend et. Te sed sale sanctus volutpat. Ei dicat nemore reformidans vim, ex
oblique theophrastus mel. 2. Qui ea atqui causae pertinax, mea soluta dissentiet no. Dicam nostrud indoctum ea vel, ad has
aliquam menandri vulputate. In agam malis molestie vis, magna nullam audiam ut quo, legendos laboramus assueverit at
est. Ad quas munere persecuti his. Augue iudico nemore his no. Nam et possit virtute. Nam ocurreret intellegam id, no hinc
aliquid epicurei eum. Quo alii expetenda expetendis in. At eos graeci equidem. Eam ea tamquam incorrupte, cum cu iudico
impedit adipiscing.
Methods
test
Results
test
Conclusion
test
Financial Disclosure (Sylvie Beaudenon-Huibregtse)
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 241
Comparison Of The Accuracy Of Hybrid Capture II (HCII) And PCR In Detecting Cervical Dysplasia: A
Systematic Review And Meta-Analysis
Author List
1. Presenting Author: Hung Luu
2. Additional Author: Kristina Dahlstrom
3. Additional Author: Patricia Mullen
4. Additional Author: Helena VonVille
5. Additional Author: Michael Scheurer
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
Table 1.jpg
Summary
Introduction
The effectiveness of screening programs for cervical cancer has benefited from the inclusion of HPV DNA assays; which
assay to choose, however, is not clear from studies conducted to date. We conducted a systematic review and meta-analysis
to compare Hybrid Capture II (HCII) and polymerase chain reaction (PCR) assays in detecting cervical dysplasia.
Methods
We searched Ovid-Medline, PubMed, and the Cochrane Library for English language studies, from any country1985-2012,
with cervical dysplasia defined by the Bethesda classification. Meta-analysis provided pooled sensitivity, specificity and
95% confidence intervals (CIs); meta-regression identified sources of heterogeneity. Covariates in meta-regression were
settings (screening vs. diagnostic), gold standard (cytology vs. histology), lesion type (ASCUS/LSIL vs. HSIL), and
location (Asia, North America, South America, and Europe). We also included PCR types (MY/PGMY 09/11, GP5+/6+,
and PCR Amplicor) as a covariate in PCR meta-regression.
Results
We identified 29 published reports from which we calculated pooled sensitivity, specificity and 95% CI to detect lesions as
follows: [Table to be inserted here]. Both assays have higher accuracy to detect cervical dysplasia in Europe than in Asia
and in North America [diagnostic Odds Ratio-dOR=4.08 and 95% CI (95% CI=1.39-11.91) and 4.56 (95% CI=1.86-11.17)
for HCII versus 2.66 (95% CI=1.16-6.53) and 3.78 (95% CI=1.50-9.51) for PCR]. Both assays also have higher accuracy
to detect HSIL than ASCUS/LSIL [HCII-dOR=9.04 (CI=4.12-19.86) and PCR-dOR=5.60 (CI=2.87-10.94)]. PCR
Amplicor and MY/PGMY 09/11 are more accurate than PCR GP5+/6+ [dOR=3.01 (CI=1.05-8.63); 2.75 (CI=1.16-6.53)
respectively]. Also, using histology as a gold standard results in higher scores for the accuracy of HCII than using cytology
[dOR=2.87 (95% CI=1.31-6.29)].
Conclusion
Our results support the use of HCII in a cervical cancer screening program. Also the role of HPV type distribution should
be explored to determine the worldwide comparability of HPV test accuracy.
Financial Disclosure (Hung Luu)
No
FDA Disclosure
Cleared:Yes
Keywords
Meta-analysis
Test Accuracy
Hybrid Capture II (HCII)
Polymerase Chain Reaction (PCR)
Abstract ID: 242
Cancer And Embryogenesis Share Common Pathways At The Molecular Level
Author List
1. Presenting Author: Mary McGuire
2. Additional Author: Robert Brown
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Biological processes normal in embryogenesis â€“ such as epithelial-mesenchymal transitions (EMT) that form new tissue
types and a low oxygen (hypoxic) microenvironment â€“ have been associated with cancerâ€™s abnormal cell structure
(morphology) since MÃ¼llerâ€™s observations in 1843. Here we used a novel combination of
morphoproteomics and biomedical analytics methods to uncover
â€œembryogenesis-likeâ€• processes in lung-metastasized renal cell (kidney) cancer (RCC) to gain insights into disease
progression and therapeutic effects.
Methods
Morphoproteomic analysis is based in anatomic pathology; it uses bright-field microscopy and
proteomics by immunohistochemistry to profile the molecular pathways in cancer tumors. The morphoproteomic tumor
profile is a list of the proteins identified in the tumor, along with their histology scores (such as stain intensity 0 â€“ 3+ or
number of high powered fields), cellular compartment locations (nucleus, cytoplasm or cell membrane) and
pathologistâ€™s comments. Biomedical analytics is the science of developing and applying
computable algorithms based on mathematics, operations research, statistics and computer science to extract properties
from biological and medical data. Two algorithms were developed: the first converted the disparate elements of the
morphoproteomic tumor profile to a scored protein list suitable for input to pathway analysis software; the second,
analyzed and compared the biological pathway networks output by the software.
Results
Two RCC tissue samples per patient were compared: one with clear cell renal carcinoma (CCRC) and one with the
aggressive sarcomatoid renal cell carcinoma (SRCC). Histologically, the SRCC morphology resembled that of cells during
EMT. Biomedical analytics showed the increased role of EMT, hypoxia and stem cell-related molecular interactions in the
SRCC tissues as well as the effects of drug interventions on the pathogenic biological pathways.
Conclusion
The combination of the traditional pathology methods used in morphoproteomics with computational
biomedical analytics supported MÃ¼llerâ€™s proposal that cancer has underlying molecular
processes similar to those of embryogenesis. We plan to continue with this approach to identify aberrant embryogenesis
processes and their pathways in a patientâ€™s tumor with the goal of personalizing therapy.
Financial Disclosure (Mary McGuire)
No
FDA Disclosure
Cleared:Yes
Keywords
Morphoproteomics
Biomedical Analytics
Embryogenesis
Renal Cell Carcinoma
Abstract ID: 243
Salud San Antonio! Promoting Breast, Cervical, And Colorectal Cancer Education Among Latinas - Results Of A
Pilot Program
Author List
1. Presenting Author: Cynthia Mojica
2. Additional Author: Daisy Morales-Campos
3. Additional Author: Christina Carmona
4. Additional Author: Yuanyuan Liang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cancer is expected to be the No. 1 cause of death in the U.S. and Texas within a decade. Despite effective screening tests
that can find cancer when treatment is more effective, Latinos are less likely than non-Hispanic White or Black Americans
to undergo recommended screening for breast, cervical or colorectal cancer. 
Salud San Antonio! (April 2010 to September 2012) had two promotoras (community health workers) at four community
based-organizations delivering a cancer education and outreach program to increase screening rates and knowledge of
breast, cervical, and colorectal cancer among â€œrarely or never screenedâ€• Latinas living in 10 zip codes in San
Antonioâ€™s West and South sides that have been identified by local health officials as high-risk areas for health
problems. 
Methods
 
Promotoras attended community events and conducted educational sessions to educate women on risk factors, screening
tests, and early detection. Knowledge was measured using surveys at recruitment and educational sessions. Promotoras
encouraged women to obtain a mammogram, Pap test, or blood stool test, referred women to local clinics offering
no/low-cost screening services, and assisted women with scheduling appointments and provided follow-up navigation. To
facilitate communication and data collection, promotoras were equipped with cellular phones and iPads with wireless
access to e-mail, Internet, and calendars.
Results
 
Promotoras reached over 4,000 women through community outreach, enrolled 445 women, and hosted 126 educational
sessions (81% attendance). Participants were a mean age of 45 years, uninsured (83%), unemployed (58%), and had a
household income < $30K (85%). Over half the women (55%) were born in the U.S., 40% in Mexico, and 5% in other
countries. Many women were primarily Spanish-speakers (45%) and 66% had < high school education. Analyses suggest
that women are not aware of the age-guidelines for breast and colorectal cancer screening: 53% of women stated that
mammograms should start at < 39 years and only 18% stated that the blood stool test should start at 50 years. Women are
fairly knowledgeable about screening for cervical cancer. In total, 152 women considered â€œrarely or never screenedâ€•
were scheduled for a screening test - 30% for a mammogram, 64% for a Pap smear, 6% for a blood stool test - and 87%
(n=132) kept their appointment. The other 293 eligible women who have not obtained cancer screening are on waiting lists
at local clinics.
Conclusion
Program participants were grateful for the education and assistance with navigation, and over 126 organizations joined our
cancer prevention efforts.
Financial Disclosure (Cynthia Mojica)
No
FDA Disclosure
Cleared:Yes
Keywords
promotoras
cancer screening
education and outreach
latinas
Abstract ID: 244
Micro RNA 665 Inhibits The Growth Of Neuroblastoma Cells
Author List
1. Presenting Author: Nagindra Prashad
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Figure1.JPG
Summary
N/A
Introduction
Neuroblastoma, (NB), is one of the most common solid tumors among the childhood cancers. NB is responsible for 15% of
all childhood deaths. Essentially all patients who have tumors with MYCN gene amplification have high-risk disease and
are also resistant to chemotherapy. Currently there is no effective treatment for the ablation of NB tumor in children
without the cytotoxic effects. In the light of the progress made in the areas of Human Genome sequencing, new targeted
molecular therapies that do not have deleterious cytotoxic effects are needed for NB treatment. Towards this end, we are
investigating the ability of the suppressor miRNA to inhibit the growth of NB. miRNAs are a conserved class of
non-coding small RNAs with 20-22 nucleotides that regulate gene and protein expression by binding to target mRNA
leading to mRNA degradation or inhibition of translation. miRNAs regulate diverse biological processes such as cell
regulation, cellular differentiation; several disease processes and play a role in cancer. Some miRNAs are oncogenic and
some are suppressor miRNAs.
Methods
The aim of this study is to investigate the role of miRNA 665 as a suppressor miRNA to inhibit the growth of NB cells.
miRNA 665 is differentially increased in induced cellular differentiated mouse NB cells. Mimic hsa-miR-665 or
mmu-miR-665 was transfected into NB cells and cell proliferation was assay by CellTiter assay, cell cycle analysis was
done by Flow cytometry and targets were identified by transfecting 3â€™-UTR of targets with luciferase fusion reporter
and miR-665 or non-targeting control miRNA.
Results
Mimic hsa-miR-665 inhibited 60% of the growth of NB cells. The growth inhibited cells were arrested in G1 phase of cell
cycle, and the percent cells in G1 phase increased and decreased in S phase. The following targets, MRTO4, SYT2,
BTN3A3, PAN2, FCRL5, WDR48, ZCCHC17 and TP53I11 were knocked down by 3 to 6-fold.
Conclusion
These results show that transfection of mimic hsa-miR-665 or mmu-miR-665 restores tumor suppressing function in NB
cells, and may work in combination with other therapeutic agents, thus providing a novel potent therapeutic approach for
the treatment of Neuroblastoma in children.
Financial Disclosure (Nagindra Prashad)
No
FDA Disclosure
Cleared:Yes
Keywords
Neuroblastoma
micro RNA
None
None
Abstract ID: 245
Protein Scaffolds For Light-Activated Delivery Of Toxic Iron To Cancer Cells
Author List
1. Presenting Author: Emily Boice
2. Additional Author: Donald Kurtz
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
A spherical, 24-subunit, iron storage protein called bacterioferritin (Bfr) has been adapted for a novel photo-initiated
approach to cancer therapy. Hydroxyl radicals generated via Fenton chemistry from photo-triggered release of iron would
overwhelm the cellâ€™s defenses against reactive oxygen species. The Bfr protein cage has been loaded with ~1,000 iron
atoms. Twelve visible/near-infrared-absorbing photosensitizers, such as zinc protoporphyrin (ZnPPIX), have been
substituted into the native heme binding sites in the protein. 24 tumor-targeting peptides (TTPs) have been fused to the
exterior surface of the Bfr protein. These peptides are designed to bind to specific receptors on the cancer cell surface.
After binding of the [Fe~1,000-(ZnPPIX)12-(TTP)24-Bfr] to cell receptors,
photo-excitation of the ZnPPIX with light would generate a highly reducing excited state, triggering release of iron.
Together with hydrogen peroxide present in aerobic or hypoxic cellular environments, the iron would generate a flux of
toxic hydroxyl radicals and overwhelm the cancer cellâ€™s defenses. In addition these TTP tags can be modified to target
specific types of cells (prostate, breast etc.).
Methods
The gene encoding the Bfr subunit fused to a TTP was synthesized and inserted into an E. coli expression
plasmid. The [ZnPPIX12-TTP24-Bfr] was readily expressed in and purified by standard
methods. The purified [ZnPPIX12-TTP24-Bfr] was then loaded with iron by anaerobic
incubation of ~2000 irons/protein followed by aerobic oxidation and centrifugation to remove unbound iron. Solutions of
[Fe~1,000ZnPPIX12-TTP24-Bfr] in 10 mM NADH, 500 mM NaCl were irradiated
with a tungsten halogen light source. Samples were withdrawn at various irradiation times, and ferrozine was added to
quantitate the iron released from the protein.
Results
These procedures reproducibly resulted in soluble TTP24-Bfr loaded with 12 ZnPPIX and ~1000 irons. After
3 hours irradiation, ~30% of the iron was released from
[Fe~1,000ZnPPIX12-TTP24-Bfr]. At longer irradiation times, 65-70% of the iron
was released. No iron was released from identical control solutions kept in the dark.
Conclusion
We have established that [Fe~1,000ZnPPIX12-TTP24-Bfr] releases significant
amounts of iron upon irradiation with visible light. Current work is aimed at assessing binding of
[Fe~1,000ZnPPIX12-TTP24-Bfr] to melanoma cells, and assessing inhibition of
cell growth or apoptosis upon light irradiation of the cells containing bound
[Fe~1,000ZnPPIX12-TTP24-Bfr]. Results of these investigations could provide
proof of principle for a new general approach to cancer therapy.
Financial Disclosure (Emily Boice)
No
FDA Disclosure
Cleared:Yes
Keywords
bacterioferritin
photosensitizer
iron
irradiation
Abstract ID: 246
Cancer Proteomics And Metabolomics Core Facility
Author List
1. Additional Author: Arun Sreekumar
2. Additional Author: Shixia Huang
3. Additional Author: Sung Yun Jung
5. Presenting Author: Dean Edwards
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cancer development and progression involves not only alterations in genes, but also protein signaling pathways and
metabolism that collectively drive the cancer phenotype. Our goal is to develop a combined Proteomics and Metabolomics
Core Facility to assist researchers with advancing integration of the triad of genomics, proteomics and metabolomics that
will be essential for personalized medicine in cancer.
Methods
A Core Facility has been set up that has three main technology platforms. These include 1) mass spectrometry
identification of endogenous protein complexes and their interacting networks led by Drs. Jun Qin and Sung Yun Jung,
using an LTQ Orbitrap Elite-1000. 2) Reverse phase protein arrays (RPA), an antibody affinity-based microarray platform
for quantitative analysis and validation of protein pathways. This is led by Drs. Dean Edwards and Shixia Huang, using
advanced protein microarray printers (Aushon 2470 Arrayer), and an inventory of validated antibodies to measure total and
phosphorylation states of several hundred proteins. 3) Targeted profiling of up to 300 metabolites by multiple reaction
monitoring (MRM) mass spectrometry led by Dr. Arun Sreekumar, using an Agilent 6490 triple quadrupole (QQQ)
instrument. The Core operates by soliciting short request for project (RFP) applications that describe the scientific
background, goals, cancer relevance and experimental outline. Projects selected by an advisory committee are scheduled
and carried out by the Core as a highly collaborative venture. The Core also conducts internal research and development
projects to advance technologies and build new assays and pathway targets as required by cancer researchers.
Results
We are midway into the first year of this CPRIT project. The goal of the first 6 months was the installation and training on
the new equipment, and hiring and training of technical staff. This has been successfully completed. The Core Facility has
initiated projects on each platform. One is to identify proteins associated with a novel tumor suppressor protein in breast
cancer by the immunoprecipitation-MS strategy with the goal of determining their functional role in cancer cell survival.
RPA assays are being built and validated for protein pathways associated with epithelial-to-mesenchymal transition (EMT)
and cancer stem cells that will be used for analysis of human breast tumor xenograft experimental models. The
metabolomics section has completed MRM analysis of the effects of drugs on perturbing metabolic profiles in melanoma
cells and the metabolic alteration in tumors regulated by nuclear transcriptional co-activators.
Conclusion
The infrastructure of the Core Facility has been set up. These and other projects will be presented in more detail.
Financial Disclosure (Dean Edwards)
No
FDA Disclosure
Cleared:Yes
Keywords
metabolomics
proteomics
core facility
None
Abstract ID: 247
A Radial Acquisition Scheme for Dynamic MRI of Hyperpolarized 13C-Labeled Metabolites
Author List
1. Presenting Author: Marc Ramirez
2. Additional Author: Jaehyuk Lee
3. Additional Author: James Bankson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
CombinedFigures.jpg
Summary
Introduction
In contrast to the high sensitivity and natural abundance of 1H nuclei in the body, in vivo imaging of the 13C isotope is not
feasible with traditional magnetic resonance imaging (MRI) techniques. Practical methods to hyperpolarize 13C-labeled
tracers have recently been developed, allowing a temporary improvement in signal-to-noise by more than three orders of
magnitude. The hyperpolarized signal is short-lived however, decaying according to T1 relaxation (on the order of tens of
seconds) and losing magnetization with every RF excitation. To gain insight into cancer metabolism, including glycolytic
and TCA cycle pathways, MRI sequences with spatial, temporal, and spectral separation must be developed. In this work,
we evaluate the feasibility of a multi-slice radial acquisition scheme conducive to a dynamic model-based image
reconstruction of distinct 13C metabolites.
Methods
A commercial multi gradient echo (MGE) imaging sequence was modified to provide a radial projection acquisition for use
on a 7-T Bruker Biospec MRI system. Resulting raw data had five dimensions including: three spatial, one projection, and
one echo/spectral dimension, which must be processed to dynamically separate the tracer from its metabolites in time and
space. To improve orthogonality of temporal sampling, the projection angle was incremented according to the golden ratio
of 111.3Â°. Lastly, a filtered backprojection reconstruction was performed on the binned data.
Results
Figure 1 demonstrates the spectral separation of spatially-localized 13C-labeled 8 M urea and 3 M acetate phantoms with
the radial MGE sequence (TE/TR = 1/1000 ms, âˆ†TE = 1.48 ms, FOV = 4Ã—4 cm, matrix = 32Ã—32, 64 echoes, 200
projections, 2 1-cm slices, 200 kHz bandwidth, 15Â° flip angle, 50 averages). The same radial MGE sequence (except
without averaging, 50Ã— shorter acquisition time, and with a 90Â° flip angle) was used to demonstrate hyperpolarized
pyruvate imaging (Figure 2).
Conclusion
In conclusion, we have implemented a radial spectroscopic MR imaging sequence that is suitable for spatial, temporal, and
spectral separation of hyperpolarized 13C-labeled tracers and their metabolic products. Future work will consist of
sequence optimization and development of a model-based constrained image reconstruction of dynamic data.
Financial Disclosure (Marc Ramirez)
No
FDA Disclosure
Cleared:Yes
Keywords
Spectroscopic MRI
Hyperpolarize
Pulse Sequence
Carbon 13
Abstract ID: 250
Therapeutic Regulation Of PI3-Kinase/AKT Signaling By MicroRNAs
Author List
1. Additional Author: Christopher DeSevo
2. Additional Author: Liqin Du
3. Additional Author: Ignacio Wistuba
5. Presenting Author: Alexander Pertsemlidis
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Figure 1.jpg
Summary
Introduction
Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes involved in diverse cellular functions including cell
growth, proliferation, differentiation, motility, survival and apoptosis. PI3K signaling is under extremely tight regulation
and even slight perturbations can lead to aberrant pathway activation, as is the case in a majority of cancers. In addition,
increased activity of PI3K has been shown to underlie resistance to several chemotherapeutic agents that are commonly
used to treat lung cancers, such as the EGFR inhibitors gefitnib and erlotinib. We are interested in whether PIK3CA is
regulated by one or more microRNAs and whether those miRNAs have a therapeutic effect on cancer cell viability and
drug response in PI3K-driven oncogenesis.
Methods
In a systematic approach to identifying miRNA inhibitors with significant effects on cell viability and response to
paclitaxel in NSCLC, we performed a high-throughput screen and identified several candidate microRNAs. Regulatory
targets of candidate miRNAs were identified through a combination of in vitro and in silico approaches. Targets were then
validated using qRT-PCR, protein quantification, and luciferase reporter assays. The response of cancer cells to
perturbations in candidate miRNA levels was assessed through flow cytometric analysis of cell cycle phase distribution and
through colony formation and caspase activation assays.
Results
Inhibition of miR-10a resulted in increased cellular growth rate and resistance to paclitaxel, with a significant increase in
both cell viability and colony formation in the presence of miR-10a inhibitor, and a significant decrease in the presence of
miR-10a mimic. Manipulation of miR-10a levels also resulted in significant changes in both mRNA and protein levels of
its predicted target, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K). Specificity of the interaction between
miR-10a and the 3'UTR of PIK3CA was confirmed by luciferase reporter assay. Levels of both miR-10a and its
target PI3K are significantly correlated with NSCLC patient survival, with median recurrence-free survival longer in
patients with high miR-10a levels and in patients with low PI3K levels.
Conclusion
The identification of a miR-10a as a modulator of cellular response to taxanes, and PI3K as a regulatory target which
mediates that response, define a novel regulatory pathway modulating lung cancer cell viability. As a negative regulator of
PIK3CA, miR-10a is potentially both a positive prognostic marker for NSCLC and the basis for a novel therapeutic
strategy. Ultimately this study will provide new insights into the molecular basis of lung cancer and a new set of potential
therapeutic targets for this devastating disease.
Financial Disclosure (Alexander Pertsemlidis)
No
FDA Disclosure
Cleared:Yes
Keywords
microRNA
lung cancer
PI3K/Akt
miR-10a
Abstract ID: 251
Degradation Of The Promyelocytic Leukemia Protein (PML) By An Oncogenic Gammaherpesvirus Modulates
Adaptive Immunity And Reactivation In Infected Mice
Author List
1. Presenting Author: Jaturong Sewatanon
2. Additional Author: Paul Ling
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Epstein-Barr virus (EBV) and Kaposiâ€™s Sarcoma herpesvirus (KSHV) are gammaherpesviruses associated with a
number of human malignancies. Many herpesviruses encode one or more proteins that induce the degradation of the
promyelocytic leukemia (PML) tumor suppressor protein. PML is mediates an intrinsic host defense against herpesvirus
infection, but the mechanism for this activity has not been elucidated. Murine gammaherpesvirus 68 (MHV68) is emerging
as a suitable model to study herpesvirus-host interactions because it naturally infects mice and can cause lymphomas. We
have previously shown that MHV68 induces PML degradation through a proteasome-dependent mechanism and is
mediated by open reading frame 75c (ORF75c), which is a protein conserved in all gammaherpesviruses. We hypothesize
that MHV68 will be a rewarding model system to address mechanisms and consequences of PML interactions with
oncogenic gammaherpesviruses. We expect this study will reveal novel insights relevant to mechanisms of carcinogenesis
and provide information that may lead to the development of novel therapies for human cancers.
Methods
To determine the mechanism by which ORF75 mediates PML degradation, we investigated whether ORF75c contains a
ubiquitin E3 ligase activity itself or stimulates other cellular factors known to regulate PML stability by using both
cell-based and in vitro systems. The role of PML in modulating the kinetics of acute and latent infection was
determined by infecting wild-type and PML-knockout mice with MHV68 or MHV68 mutant viruses unable to induce PML
degradation. The development of splenomegaly, viral titers in lungs and spleens, and reactivation frequency from
splenocytes and peritoneal exudate cells (PECs) were measured in infected animals.
Results
We found that highly purified ORF75c increased the overall level of ubiquitin-conjugates and showed self-ubiquitination
activity in vitro. ORF75c interacted weakly with mouse PML but this was sufficient to increase PML
polyubiquitination in cell-based system. We also demonstrated that known cellular PML regulators, Casein kinase II (CK2)
and human papilloma virus E6-associated protein (E6AP), have no role in ORF75c-mediated PML degradation. Results in
animals showed that the ability to degrade PML may affect on the development of splenomegaly and the clearance of acute
infection from the lungs. It is also interesting that both wild-type and PML-degradation deficient viruses reactivate with
higher frequencies from PECs harvested from PML-knockout mice at 42 days post-infection compared to wild-type mice.
Conclusion
MHV68 ORF75c mediates PML degradation through its ubiquitin E3 ligase activity and PML might have roles in
modulating host adaptive immune responses and reactivation of oncogenic gammaherpesviruses from macrophages.
Financial Disclosure (Jaturong Sewatanon)
No
FDA Disclosure
Cleared:Yes
Keywords
Promyelocytic leukemia protein (PML)
Oncogenic gammaherpesvirus Open Reading Frame 75c (ORF75c)
Viral ubiquitin E3 ligase
Adaptive-immunity modulation
Abstract ID: 252
Understanding Interactions Of Canonical And Non-Canonical NF-kB Pathways In Cancer
Author List
1. Presenting Author: Mridul Kalita
2. Additional Author: Ling Fang
3. Additional Author: Sanjeev Choudhary
4. Additional Author: Allan Brasier
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
Introduction
Constitutive NF-kB activation has been associated with numerous human cancers; however the role of non-canonical
component of NF-kB pathway in cancer development is not well investigated. NIK stabilization and subsequent
NF-kB2/p100 processing to p52 is a characteristic feature of non-canonical pathway activation, resulting into induction of
set of genes involved in cancer development. Although the activation of non-canonical pathway is facilitated by the
activation of canonical pathway, little is known about the molecular linkages between these two components. Here, we
have undertaken an integrated experimental-computational analysis to investigate the mechanism by which these two
pathways are coupled after tonic TNF stimulation. A deterministic mathematical model of the canonical-non-canonical
pathway was developed and many simulations were experimentally validated. The integrated computational modeling and
experimental analysis identified a unique and essential role of NIK and TRAF1 mediated activation of non-canonical
pathway in cancer
Methods
TNF stimulation leads to delayed activation of the non-canonical pathway in A549 human alveolar adenocarcinoma cells.
Gene expression microarray showed a rapid induction of TRAF1 mRNA by TNF stimulation, prior to p100 processing.
The association of other TRAF proteins and functional role of TRAF1 in particular in the stabilization of NIK protein was
studied by various assays such as immunoprecipitations and Western blots. We further extended our previously published
canonical NF-kB model by incorporating experimentally measured concentrations and reaction steps of non-canonical
pathway. Addition and fitting of new parameters and reaction steps did not alter the canonical NF-kB dynamics. We
performed various simulations including in silico knockouts to understand the transition from canonical to
non-canonical pathway dynamics.
Results
Findings from wet-lab experiments suggest the critical role of TRAF1 in NIK stabilization and subsequent p100 processing
to p52. The simulated kinetic-profiles of NF-kB induced rapid expression of TRAF1 and delayed p100 proteins and its
processing to p52 provided an in silico confirmation of our experimental results. The in silico
knockout simulations and subsequent experimental validations revealed the functional implication of TRAF1 and NIK in
p100 processing. Simulations also suggest that the time-delay in non-canonical pathway activation is sensitive to
synergistic action of both TRAF1 kinetics and p100 processing.
Conclusion
The newly developed mathematical model significantly refined the understanding about the dynamics and crosstalk of two
arms of NF-kB pathway, and its potential role in cancer.
Financial Disclosure (Mridul Kalita)
No
FDA Disclosure
Cleared:Yes
Keywords
mathematical modeling
non-canonical NF-kB pathway
crosstalk
cancer
Abstract ID: 253
Comparison Of Organized FIT Invitation, Organized Colonoscopy Invitation, And Usual Care For Colorectal
Cancer Screening Among The Undeserved.
Author List
1. Presenting Author: Samir Gupta
2. Additional Author: Marcia Hammons
3. Additional Author: Luisa Valdez
4. Additional Author: Elizabeth Carter
5. Additional Author: Mark Koch
6. Additional Author: Liyue Tong
7. Additional Author: Chul Ahn
8. Additional Author: Don Rockey
9. Additional Author: Jasmin Tiro
11. Additional Author: Ethan Halm
12. Additional Author: Celette Skinner
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Screening may prevent colorectal cancer (CRC) mortality, but participation remains suboptimal, particularly among the
underserved. Optimal approaches to boost screening, including best test(s) to offer, are unknown. For our
CPRIT-sponsored Evidenced Based Prevention Program, we proposed that an organized, health system level screening
invitation approach, in which patients not up-to-date with screening were invited to complete screening by mail, could be
used to boost screening and determine effectiveness when different screening tests were offered. Accordingly, at John Peter
Smith Hospital (JPS), the primary safety-net health system for Tarrant County, Texas, we compared three approaches to
boosting screening among the underserved: 1) Organized invitation to a fecal immunochemical test (FIT), 2) Organized
invitation to colonoscopy, and 3) Usual Care.
Methods
Patients age 54-64 years, not up-to-date with screening, who were uninsured except for participation in a JPS medical
assistance program for the underserved were eligible. Patients were randomly assigned to: 1)Organized mailed invitation to
FIT screening, with a FIT kit included, 2)Organized mailed invitation to colonoscopy screening, or 3)Usual Care. Usual
Care through the JPS medical assistance program includes opportunistic, visit-based offers for CRC screening at the
primary providerâ€™s discretion; organized invitation groups also received Usual Care. We used telephone calls to
promote screening, assist with test scheduling, and facilitate abnormal test follow-up. Primary outcome was screening
participation (of any test type) at 1 year. Secondary outcomes included neoplasia detection.
Results
5,994 patients were assigned to organized FIT (n=1,593), organized colonoscopy (n=479), or Usual Care (n=3,898) groups.
Across groups, sex and race/ethnicity were similar; 64% were female; 41.0% White, 23.6% Black, 28.5% Hispanic, and
6.8% other race/ethnicity. Screening participation at one year was significantly higher for patients receiving organized
invitations versus usual care (37% versus 12.1%), and for patients receiving organized FIT versus colonoscopy invitations
(40.7% versus 24.6%), p<0.0001 for all comparisons. Similar results were noted for White, Black, and Hispanic patients on
analyses stratified by race/ethnicity, p<0.05 for all comparisons. 3 patients in the organized FIT, and 1 patient in the
organized colonoscopy group had screen-detected CRC.
Conclusion
Organized mailed invitation to screening resulted in markedly higher screening rates among underserved patients in a
safety-net setting after just one year. Organized invitation was most effective at improving screening when FIT rather than
colonoscopy was offeredâ€”an over 15% absolute difference. We predict that organized invitation approaches for
screening among the underserved would boost screening, and therefore merit implementation.
Financial Disclosure (Samir Gupta)
material? Yes
- Donated FIT test kits - Polymedco
FDA Disclosure
Cleared:Yes
Keywords
underserved population
fecal immunochemical test
colonoscopy
safety net
Abstract ID: 255
Maximizing Cancer Survivorship: Implementation Of An Evidence-based Exercise Program
Author List
1. Presenting Author: Stacey Young-McCaughan
2. Additional Author: Ann Newsted
3. Additional Author: Daniel Hughes
4. Additional Author: Jennifer Shaw
5. Additional Author: Nick Davies
6. Additional Author: Jeff Monaco
7. Additional Author: Sonya Arzola
8. Additional Author: Virginia Tovar
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
 
A growing body of research investigating exercise rehabilitation in patients with cancer has documented dramatic
improvements in both physiological and psychological functioning. Translating what is known of how exercise improves
health and functioning for cancer survivors is the objective of this ongoing evidence-based prevention project.
Methods
 
The goal of this program is to provide cancer survivors with a comprehensive fitness assessment and individualized
exercise program specific to their cancer diagnosis and treatment, medical history, fitness levels, and personal preferences..
From a comprehensive fitness evaluation using American College of Sports Medicine (ASCM) recommendations, an
exercise prescription is developed considering frequency, intensity, time, type, and progression of exercise. Opportunities
for individuals to implement their exercise program include both a supervised clinic-based program as well as a
home-based program.
Results
 
In the first nine months of the program, 145 cancer survivors and 45 family members or friends have been assessed. The
program continues to enroll new participants. Of the 145 survivors enrolled to date and who are currently exercising,
three-quarters are women (n = 109, 75%); one-third identifies themselves as Hispanic or Latino (n = 52, 36%). The
youngest survivor is 15, the oldest 87 (mean age = 59 Â±11.4). One-third of the group reports a household income less
than $35,000. Survivors report 14 different cancer diagnoses; primarily breast, prostate, and colon cancers; and all stages of
disease. One-third of the sample (n = 48, 33%) reports having stage III or IV disease. The average time from diagnosis is
five years, although one-quarter of the participants are in the first year of their survivorship. Program participants report an
average of four co-morbidities; only 14 survivors (10%) could be considered â€œapparently healthyâ€• by ACSM
standards; the other 131 were assessed as being at increased risk. The survivors reported various motivations for joining the
program including weight loss, to feel better, and increase energy. In the 48 survivors who have completed 4-months in the
program, significant improvements in time on the treadmill during testing, predicted VO2max, and lower
extremity strength were found, as well as trends towards improved general health and fewer limitations in physical
functioning.
Conclusion
 
This evidence-based program has been very well-received by the community of cancer survivors and their family
members. Data will continue to be collected documenting program effects on quality of life, exercise tolerance, balance,
and physiological parameters of health as well as programmatic barriers and facilitators.
Financial Disclosure (Stacey Young-McCaughan)
No
FDA Disclosure
Cleared:Yes
Keywords
exercise
survivorship
evidence-based program
quality of life
Abstract ID: 256
Identifying Novel Cancer Susceptibility Genes Through Exome Sequencing And Copy Number Analysis Of
Individuals With Li Fraumeni-like Cancer Phenotypes
Author List
1. Presenting Author: Bradford Powell
2. Additional Author: Deborah Ritter
3. Additional Author: Hannah Cheung
4. Additional Author: Louise Strong
5. Additional Author: David Wheeler
6. Additional Author: Richard Gibbs
7. Additional Author: Sharon Plon
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The identification of mutations in specific genes responsible for inherited cancer susceptibility impacts patient treatment
and allows appropriate surveillance and prevention for at-risk family members. In addition, knowledge of inherited
predisposition to pediatric malignancies has provided important insights into the mechanisms of cancer in both children
and adults. Utilization of high-throughput sequencing methodologies for detecting coding changes in cancer has been
focused on somatic mutations in tumor tissue; conversely, genome-wide association studies of cancer susceptibility have
focused on common variations that individually have small impacts on cancer risk.
Methods
We are undertaking massively parallel sequence analysis of constitutional DNA from ethnically diverse childhood cancer
patients with family histories suggestive of inherited cancer susceptibility syndromes. Patients are enrolled through cancer
genetics protocols at several institutions in Texas. We are analyzing small cohorts of families with consistent and specific
phenotypes, including probands with childhood sarcomas and second or third primary malignancies by age 40, highly
suggestive of the Li Fraumeni syndrome, but where thorough sequence and copy number analysis of TP53 and
other well-characterized cancer-associated genes has been negative.
Results
We have identified eight unrelated individuals who meet these criteria, the majority of whom have either negative family
history or a single affected first-degree relative consistent with autosomal dominant inheritance. Capture of coding regions
using a vCrome 2.1 platform was followed by Illumina paired-end exome sequencing performed on constitutional DNA
from blood or lymphoblastoid line and analyzed for novel or rare mutations which are predicted to impact gene function.
Rare copy number variants were determined using Affymetrix high-density arrays. Given the limited availability of family
samples, genes will be prioritized for further analysis by the identification of deleterious variants or CNVs in multiple
independent probands. Because the cancer susceptibility phenotypes in these families are rare, initial analysis has focused
on rare (population allele frequencies < 1%) heterozygous variants. With exclusion of genes for which truncating mutations
are frequently seen in other populations, preliminary analysis reveals 70 genes in which four or more individuals have a
rare variant predicted to alter protein sequence. Of these, 38 genes have rare single nucleotide nonsynonymous or nonsense
variants in four or more individuals. Copy number analysis revealed no shared events in multiple individuals.
Conclusion
Genome-scale sequencing and copy number analysis followed by functional analyses should allow identification of
causative mutations in individuals with p53-like cancer phenotypes in the absence of extended family information.
Financial Disclosure (Bradford Powell)
No
FDA Disclosure
Cleared:Yes
Keywords
cancer genetics
exome sequencing
diagnostic testing
bioinformatics
Abstract ID: 257
Combining STAT3 Inhibition With T-Cell Immunotherapy For The Treatment Of Glioblastoma
Author List
1. Presenting Author: Swati Naik
2. Additional Author: David Torres
3. Additional Author: Kevin Chow
4. Additional Author: Xin Long
5. Additional Author: David Tweardy
6. Additional Author: Michele Redell
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Despite multi-modality therapy, the outcome of glioblastoma (GBM) remains dismal, and T-cell immunotherapy is one
promising approach to improve outcomes. We have shown that T cells expressing EphA2-specific chimeric antigen
receptors (EphA2-specific T cells) induce regression of EphA2-positive GBMs in preclinical animal models. About Â½ of
the treated animal had long lasting complete responses, and we are now exploring several strategies to enhance the
anti-GBM activity of our T-cell therapy approach for glioma. STAT3 is a transcription factor that is constitutively
phosphorylated (active) in GBM. It is critical for the malignant phenotype of glioma cells including glioma-initiating cells
and contributes to immune evasion strategies employed by gliomas. The goal of this project was now to determine if
combining STAT3 inhibition with EphA2-specific T cells enhances anti-glioma effects.
Methods
We evaluated the anti-tumor activity of EphA2-T cells in the presence of the STAT3 inhibitors in response to GBM cells in
vitro. For the STAT3 inhibitors, we used i) Stattic, a commercially available STAT3 inhibitor and ii) Compound188-9, a
novel STAT3 inhibitor. We used standard assays including cytotoxicity and proliferation assays, neurosphere assays and
FACS.
Results
The STAT3 inhibitors Stattic and C188-9 inhibited the phosphorylation of STAT3 at low micromolar doses in GBM cell
lines (U87, U373) resulting in dose-dependent cell death. To evaluate if STAT3 inhibition in combination with EphA2-T
cells enhances antitumor effects, U373 cells were treated with Stattic before the addition of T cells. While Stattic and
EphA2-specific T cells alone induced significant cell killing, the combination of Stattic and EphA2-specific T cells was
more effective in eradicating glioma cells (p<0.001). To evaluate if STAT3 inhibition in combination with EphA2-specific
T cells is also effective against glioma-initiating cells, we performed experiments with secondary neurospheres. As with
adherently grown glioma cells, the combination of Stattic or C188-9 and EphA2-specific T cells was superior (p<0.05) in
inducing cell killing. This effect was not observed when STAT3 inhibitors were combined with non-specific T cells.
Conclusion
Combining STAT3 inhibitors with EphA2-specific T cells results in enhanced glioma cell killing in vitro warranting
further exploration in preclinical glioma models. STAT3 inhibitors may not only improve current immunotherapy
approaches for glioma but also for other malignancies in which STAT3 is constitutively activated.
Financial Disclosure (Swati Naik)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 258
Metabolic Diversity In Human Non-Small Cell Lung Cancer
Author List
1. Additional Author: Pei-Hsuan Chen
2. Additional Author: Hyun Seok Kim
3. Additional Author: Rebecca Britt
6. Presenting Author: Ralph Deberardinis
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Cancer cells display oncogene-driven rewiring of metabolism to produce energy and macromolecules for growth.
Inhibition of growth-promoting metabolic pathways may prove to be a useful therapeutic strategy in cancer. We previously
identified distinct metabolic platforms that enabled cancer cells to produce macromolecular precursors from glucose and
glutamine, the two most abundant nutrients. However, neither the full breadth of cancer cell metabolic diversity, nor the
complement of mechanisms by which tumor mutations elicit metabolic reprogramming, are known. Because metabolic flux
can be analyzed in vivo without any a priori knowledge of tumor genetics or drug sensitivity, metabolic phenotyping could
produce actionable biomarkers to optimize therapy. Here we used a well-characterized panel of lung cancer cell lines to
develop the most comprehensive view of cancer cell metabolism to date. 
 
Methods
100 non-small cell lung cancer cell lines will be analyzed for a set of metabolic parameters. These cell lines stem from a
CPRIT project (RP110708) to identify biomarkers and drug targets in lung cancer. Consequently, these cell lines are
subjected to extensive genomic, epigenetic, and gene expression analysis, and are tested for sensitivity to chemotherapeutic
agents and genome-wide siRNA screens. These rich data sets will streamline the establishment of novel correlations
between metabolism and molecular/cell biological features. All cell lines are characterized for nutrient utilization, nutrient
addiction, and focused flux assays to trace the metabolism of isotope-labeled glucose and glutamine in culture. Subsequent
experiments will analyze metabolism of the same cells grown orthotopically in the lung.
Results
The 70 cell lines analyzed to date displayed surprising metabolic heterogeneity. Although all cells used glucose and
glutamine to produce biosynthetic precursors, contributions of these two nutrients varied considerably, as did the pathways
used. For individual isotopic labeling patterns, differences of >30-fold were observed across the panel. Unsupervised
clustering produced two metabolic superfamilies differentiated by relatively high or low contribution of glutamine carbon
into precursor pools, as well as numerous subfamilies and at least two outliers with novel metabolic patterns. Although
KRASÂ¬-mutant cells were distributed across both families, cells derived from large-cell tumors aggregated into the
glutamine-avid superfamily. Ongoing work will examine the ability of metabolic phenotyping to predict combinatorial
mutations and vulnerabilities to drugs and siRNAs.
Conclusion
Focused metabolic assays can produce a highly informative view of the cell-autonomous metabolic versatility among large
panels of cell lines. We expect that metabolic phenotyping of cancer cells will predict both tumor genetics and drug
sensitivity.
Financial Disclosure (Ralph Deberardinis)
material? Yes
- Peloton Therapeutics
- Glaxo-SmithKine
- Pfizer
- Genentech
FDA Disclosure
Cleared:Yes
Keywords
metabolism
biomarker
lung
screening
Abstract ID: 259
Translational Research In Cancer Metabolism At UT-Southwestern
Author List
1. Presenting Author: Ralph Deberardinis
4. Additional Author: Elizabeth Maher
5. Additional Author: Changho Choi
6. Additional Author: Isaac Marin-Valencia
7. Additional Author: Matthew Merritt
8. Additional Author: Robert Bachoo
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Altered energy metabolism is considered to be a hallmark of malignancy and a source of novel biomarkers and therapeutic
targets for cancer in humans. There is now intense interest in understanding the molecular basis of metabolic
reprogramming in cancer cells, and in particular to develop translational approaches to investigate these processes in mice
and humans. Capitalizing on CPRIT-funded projects and engaging the expertise and infrastructure for in vivo metabolic
imaging at UT-Southwestern, we have established a center of excellence for translational studies in cancer metabolism.
Our goal is to generate robust systems to analyze metabolism in cancer cell lines, primary tumor tissue, mouse models of
cancer, and human cancer patients, with a focus on improving the basic understanding of metabolic reprogramming and on
developing clinical tools to diagnose, monitor and treat cancer.
Methods
We use a broad complement of cutting-edge approaches to achieve a comprehensive view of metabolism in culture and in
vivo. Analytical methods include mass spectrometry for targeted metabolomics and metabolic flux profiling,
13C NMR spectroscopy, high-field proton magnetic resonance spectroscopy, positron emission tomography,
and real-time imaging of metabolic flux using hyperpolarized 13C. Key interdisciplinary personnel on the
team include clinical oncologists, radiologists, pathologists, physicists, chemists and molecular/cellular biologists.
Results
Since the inception of these efforts in 2009, we have primarily focused on high-grade tumors in the brain. Key, published
discoveries from the interdisciplinary team so far have included: â€¢ identification of a novel metabolic pathway in cancer
cells; â€¢ the first detailed description of nutrient metabolism in live, orthotopically-transplanted human gliomas grown in
the mouse brain; â€¢ the first successful efforts to measure glucose-dependent metabolic fluxes in vivo in human gliomas
and brain metastases; â€¢ application of high-field spectroscopy to human brain tumor patients, culminating in reliable
methods to detect and quantify biologically relevant metabolites non-invasively; â€¢ development of new, dynamic
13C hyperpolarization-based approaches to quantify metabolic fluxes in cells and mouse tumors; â€¢ the
establishment of an approach to non-invasively image the oncometabolite 2-hydroglutarate in human gliomas.
Conclusion
A highly-integrated, interdisciplinary approach to translational studies in cancer metabolism has been developed with
strong support from CPRIT. These efforts have produced a multidimensional view of metabolism in cancer cells, mouse
models of cancer, and human cancer patients. We anticipate that the versatility of these approaches will allow many of
them to be readily applied to other forms of cancer, and to be disseminated throughout Texas.
Financial Disclosure (Ralph Deberardinis)
material? Yes
- Peloton Therapeutics
- Glaxo-SmithKline
- Pfizer
- Genentech
FDA Disclosure
Cleared:Yes
Keywords
Metabolism
Imaging
Biomarkers
Glioma
Abstract ID: 260
A Genome-Wide Study Of The Role Of TET1 In DNA Methylation
Author List
1. Presenting Author: Chunlei Jin
2. Additional Author: Yue Lu
3. Additional Author: Marcos Estecio
4. Additional Author: Michelle Barton
5. Additional Author: Jean-Pierre Issa
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
DNA methylation at the C5 position of cytosine (5-methylcytosine; 5mC) is a crucial epigenetic modification of the
genome and has been implicated in numerous cellular processes in mammals, including embryonic development,
transcription, X chromosome inactivation, genomic imprinting and chromatin structure. The ten-eleven translocation
family proteins (TET1/2/3) were recently identified as 5mC dioxygenases, which consecutively convert 5mC into
5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine. Based on their potent oxidative activities on
5mC, TET proteins may work as DNA demethylases that induce DNA demethylation through multiple potential
mechanisms. Although TET1 has been well studied for its biological role in embryonic stem cells, its specific effect on
DNA methylation still remains unclear.
Methods
Human TET1 cDNA was cloned and transiently overexpressed it in HEK293T cells. Genome-wide analysis of DNA
methylation was performed using the digital restriction enzyme analysis of methylation developed by our lab. hMeDIP-seq
was used to detect the distribution of 5hmC in genomic DNA. ChIP-qPCR was explored to investigate TET1 occupancy in
certain genomic regions.
Results
Overexpression of full length TET1 in HEK293T cells failed to induce a significant DNA demethylation in any genomic
regions, in spite of a global DNA demethylation observed in cells overexpressing TET1 catalytic domain (TET1-CD).
Genome-wide mapping of 5hmC further revealed a unique regulation pattern of 5mC by TET1, where its 5hmC production
is relatively inhibited as local basal DNA methylation levels increases. By contrast, TET1-CD overexpression showed a
strong positive correlation between 5hmC yield and local basal DNA methylation levels. Moreover, through CXXC
domain TET1 is specifically enriched in hypomethylated but not hypermethylated CpG-rich regions. Finally, we also found
that TET1 knockdown led to increased DNA methylation levels in TET1-bound regions, indicating a role of TET1 in
maintaining hypomethylated state in CpG -rich regions.
Conclusion
These findings reveal that TET1 is a unique DNA demethylase which is not intended to change DNA methylation levels,
but rather specifically maintains DNA hypomethylation state in CpG-rich regions.
Financial Disclosure (Chunlei Jin)
No
FDA Disclosure
Cleared:Yes
Keywords
DNA methylation
TET1
None
None
Abstract ID: 261
An Interactome Of Tumorigenic Factors Connected Through Tumor Suppressor MiR-198 Serves As A Prognostic
Marker Signature For Pancreatic Cancer
Author List
1. Presenting Author: Christian Marin-Muller
2. Additional Author: Uddalak Bharadwaj
3. Additional Author: Min Li
4. Additional Author: Changyi Chen
5. Additional Author: Sally Hodges
6. Additional Author: William Fisher
7. Additional Author: Mien-Chie Hung
8. Additional Author: Qizhi Yao
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Indtroduction 
 
We have identified a novel network of tumorigenic prognostic factors that plays a critical role in advanced pancreatic
cancer (PC) pathogenesis. This interactome is interconnected through a central tumor suppressive microRNA, miR-198,
which is able to both directly and indirectly modulate expression of the various members of this network to alter the
molecular makeup of pancreatic tumors, with important clinical implications. When this tumor signature network is intact,
miR-198 expression is reduced and patient survival is dismal; patients with higher miR-198 present an altered tumor
signature network, better prognosis and increased survival. MiR-198 replacement reverses tumorigenicity in vitro and in
vivo, indicating the therapeutic potential of attacking a complex heterogeneous network of factors through a central
vantage point.
Methods
Methods 
Real-time RT-PCR and western blotting was used to examine the expression of the tumorigenic factors mesothelin
(MSLN), NF-ÎºB, and the homeobox transcription factors (TFs) POU2F2 (OCT-2), Pre-B-cell leukemia homeobox factor 1
(PBX-1), and Valosin-containing protein (VCP) in pancreatic cancer (PC) patient tumor and adjacent normal tissues and
PC cell lines. miR-198 oligonucleotides and lentiviral expression vectors were used to examine the effects of miR-198
replacement in vitro and in vivo, in both orthotopic and subcutaneous nude mouse models of PC.
Results
Results
We demonstrate that several heterogeneous prognostic factors for pancreatic cancer, including OCT-2, MSLN, PBX-1 and
VCP are interconnected through modulation of a central tumor-suppressive miRNA, miR-198. Our study reveals that PC
patient survival is closely associated with high miR-198 levels resulting in modulation of expression of the members in this
interactome. MiR-198 replacement reverses tumorigenicity in vitro and in vivo, indicating the therapeutic potential of
attacking a complex heterogeneous network of factors through this central vantage point. 
Conclusion
Conclusion 
The approach of studying a single molecule in an effort to identify effective anti-tumor targets is quickly being replaced by
a system-wide approach to dissect the complex interactions between genes, RNA, and proteins in regulating tumor
progression. Here, we present a unique perspective on the interplay between several factors in a functional network,
approaching the study of the effects of a single, central microRNA from a network biology framework. We have uncovered
a novel functional interactome in PC and dissected the mechanisms through which a central miRNA can alter the molecular
makeup of pancreatic tumors, with significant clinical implications warranting further study for therapeutic development.
Financial Disclosure (Christian Marin-Muller)
No
FDA Disclosure
Cleared:Yes
Keywords
microRNA
pancreatic
biomarker
interactome
Abstract ID: 262
The State Of Colorectal Cancer (CRC) In Texas In The 1st Decade Of 21st Century And Implications For Cancer
Control
Author List
1. Presenting Author: Davor Vugrin
Oral Sessions
Oral Sessions
Status
Accepted
October 25, 2012 @ 03:10 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Colorectal cancer is common and the 2nd leading cause of cancer death among Texans It is also potentially one of the most
preventable and curable cancers. In the 1990s a call to action was issued with goals by 2015 to increase up to 75% the
number of 50 year and older individuals undergoing screening per the national guidelines, and to reduce age-adjusted CRC
incidence to 34.8/100,000 and mortality to 12.0/100,000. The purpose of this study is to determine progress and trends
toward meeting the 2015 objectives for Texas.
Methods
The Texas Cancer Registry 2000 to 2009 data of the at risk population was evaluated as to invasive CRC cases diagnosed,
number of deaths, age-adjusted incidence and mortality rates, and correlation with gender, race and anatomical location.
Results
The Texas population during the study period was Non-Hispanic Whites (NHW) 50.1%, Hispanics 34.7% and Blacks
12.1%. Incidence: 91,260 invasive CRC were diagnosed with an average age-adjusted rate (aAART) of 46.8/100,000 with
10-year trend (10YT) declining from 50.4 down to 41.2. Males accounted for 53.5% of cases with aAART 56.6 and 10YT
from 61.1 to 49.3. Females accounted for 46.5% of cases with aAART 39.1 with 10YT from 42.1 to 34.5. Non-Hispanic
Whites accounted for 66.4% of cases, aAART 46.6 and 10YT 50.8 to 40.8. Hispanics contributed 18.7% of cases and had
aAART 40.7% and 10YT from 42.6 to 37.5. Blacks accounted for 12.6% of cases but had aAART of 62.2% with 10YT
declining from 64.2 to 54.40. Black males had aAART of 74.7 and females 53.6. Hispanic males aAART was 51.0 and
females 32.7. Mortality: 32,929 died from CRC with aAART of 17.3 with 10YT declining from 19.2 to 15.4. Rates were
influenced by gender, race and location of cancer.
Conclusion
Incidence rates showed a gradual decline but not at a sufficient rate to reach the 2015 goals. Declines were observed in
Non-Hispanic Whites and Blacks, but were minimal in Hispanics. Observed improvements were mainly observed for
cancers located in the colon. Rectal cancers did not show any significant decline. CRC mortality rate decline was much
more modest and seen mainly in Non-Hispanic White and Black population and not in Hispanics. We conclude that to
reach the 2015 target, it would require centralized planning, funding and coordination.
Financial Disclosure (Davor Vugrin)
No
FDA Disclosure
Cleared:Yes
Keywords
colorectal cancer
incidence rates
mortality rates
2015 colorectal cancer control goals
Abstract ID: 263
Having Healthy Conversations: The Evolving Role Of Oncology Advanced Practice Nurses In Facilitating Advance
Care Planning In Stage IV Populations
Author List
1. Presenting Author: Sabrina Mikan
2. Additional Author: Patricia Carter
3. Additional Author: Deb Harrison
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Oncology advanced practice nurses (APNs) can identify patient values and improve end-of-life care satisfaction by
facilitating interdisciplinary advance care planning (ACP) meetings in specific Stage IV populations. APNs who introduce
ACP to specific stage IV cancer patients can decrease the stigma of these conversations. This in turn â€œnormalizesâ€•
important conversations, improving quality patient care and the rate of ACP documentation (e.g. Advance Directives,
Medical Power of Attorney, Out-of-Hospital-Do-Not-Resuscitate documents). Purpose: To identify ACP Metrics within an
oncology-specific electronic health record (EHR) in order to develop strategies APNs can use to increase healthcare
provider awareness of ACP sessions and completion of documentation.
Methods
Patients with stage IV colon, lung, breast, and pancreatic cancers were identified by oncologists and referred through
physicianâ€™s orders to the APN for ACP meetings. The APN held two meetings with the patient and family. Meetings
consisted of values assessment, ACP education and discussion of patient wishes regarding illness and end-of-life care.
Results
A historical chart review revealed 2,746 patients met Stage IV criteria between January 2009 - March 2012. During this
timeframe, 59 patients had an ACP introduction, 95 had evidence of advance directives, and 230 were referred to hospice.
This ongoing project is focused on finding ways to improve these service rates. Since implementing the new intervention in
March 2012, 30 patients have been referred for ACP. A 12% increase over past rates.
Conclusion
Oncology APNs can facilitate ACP conversations to assist in identifying patient values and improve end-of-life care
satisfaction. ACP documentation in the EHR for Stage IV cancer patients is essential to provide seamless transitions in
medical care. Documentation supports patient-directed care.
Financial Disclosure (Sabrina Mikan)
No
FDA Disclosure
Cleared:Yes
Keywords
Advance Care Planning
Stage IV Cancers
Oncology Advanced Practice Nurses
Patient-directed care
Abstract ID: 264
Mapping The Regulatory Structure Between Two Key Transcription Factors In A Breast Cancer Cell Line
Author List
1. Presenting Author: Jinho Lee
2. Additional Author: Victor Shum
3. Additional Author: Michael Mancini
4. Additional Author: Oleg Igoshin
5. Additional Author: Gabor Balazsi
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Estrogen receptor alpha (ERa) expression is an essential criterion for breast cancer subtype classification. Therefore,
understanding ERa regulation can be important for improving the efficiency of current therapeutic strategies for breast
cancer. ERa and another transcription factor, GATA3 were suggested to have mutual regulatory positive feedback loops,
which may contribute to the ERa expression pattern. On the other hand, a clear understanding of the precise mechanisms of
this regulatory structure is still unclear. Therefore, we hypothesized that the network module containing the two mutually
activating transcriptional factors, ERa and GATA3, serves as a control unit which plays a central role in determining ERa
expression. In this study, we examined and validated ERa-GATA3 regulatory structure in T47D ERa-positive breast cancer
cell line through the analysis of experimental data combined with computer-based simulation and mathematical modeling.
Methods
By measuring the response of the ERa-GATA3 regulatory network to various perturbations and fitting a set of quantitative
gene regulation models to the data, we identified the regulatory structure between ERa and GATA3. For this, we
performed various cellular and biochemical experiments, including population average-level (Western blotting, RT-qPCR),
single cell-level (flow cytometry) and single nucleus level measurements (Immunofluorescence), to examine the function
of the gene regulatory structure involving ERa and GATA3 in the T47D ERa-positive breast cancer cell line. In parallel,
using semi-phenomenological method (Hill function, co-operativity), we established a mathematical model of the mutual
gene regulatory structure between ERa and GATA3. We also validated all possible 81 model systems which may exist in
the network and identified the potential parameters to control ERa expression by fitting with experimental data set.
Results
We observed cell line-dependent mutual gene regulation showing compromised ERa regulatory effect on GATA3, and
interestingly ERa negatively regulates GATA3. These observations underline the importance of cross-comparing and
interpreting increasingly detailed levels of measurement. Moreover, we established a quantitative gene regulation model
and identified the parameters to control ERa expression. The mathematical approach confirmed that our proposed model
can be described as a representative regulatory model of ERa and GATA3 in the T47D cell line.
Conclusion
Our results suggest more precise regulatory architecture between ERa and GATA3 including negative feedback and
proposed several possible regulatory modes may exist between ERa and GATA3 in the T47D breast cancer cell line. This
finding provides a new approach in understanding of breast cancer gene regulation through predictive mathematical
modeling. 
 
 
Financial Disclosure (Jinho Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast cancer
Estrogen receptor alpha
GATA3
Gene regulatory network Mathematical model
Abstract ID: 266
Identification Of Oncogenic Pathways Of Cholangiocarcinoma By Using A Novel Gene Signature Scoring Method
Author List
1. Additional Author: Tzu-Hung Hsiao
2. Additional Author: Hung-I Chen
3. Additional Author: Sarah Comerford
4. Additional Author: Gail Tomlinson
5. Presenting Author: Yidong Chen
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The activities of cellular functions and biological processes in the protein level are generated from the alteration of gene
expression profiles in cell. Therefore, the underlying mechanisms of a tumor may be delineated through observation of
gene expression profile. While earlier attempts focus on individual gene expression alteration, several recent studies utilize
gene signature set (GSS, a set of genes derived from differential expression under specific experimental condition) to
explain the biological characteristic of tumors. 
Methods
Here we present a novel sample scoring method called Signature-score (S-score) to quantify the
expression pattern of tumor samples by using gene signature sets. Different from common approach, we incorporated the
effect of differential expression significance and directionality. Let Ï•j and
pj be the fold change and p-value, respectively, of gene j between case
and control experiment from which the GSS was derived. For a GSS with N genes, the S-score of the testing
sample l is defined as sl=1/K âˆ‘ [sign(Ï•j )
p*j zj,l], where zj,l
is the z-score of jth gene expression value of lth sample evaluated across all samples. A total of 31 gene sets
were genereated from various studies to form our proposed GSSs, which includes The cell cycle signature (proliferation),
wound healing signature (progression), KRT19 and EpCAM (hepatocellular carcinomas (HCC) specific), and other
important cancer signature sets such as c-Met, TGF-beta, shh, RAF, MEK, p53, p63, Myc, AKT, PI3K, IFN-alpha,
beta-Catenin, EGFR, Ras and other signatures. 
Results
We first used a simulation approach to demonstrate an improved accuracy and robustness by S-score method
comparing with other scoring methods. We then applied the S-score method to cholangiocarcinoma (CGC), a
cancer that arises from the cells within the bile ducts of liver, and identified enriched oncogenic pathways in two CGC data
sets. 13 pathways showed the enrichment in CGC comparing with normal liver and bile duct tissues. The correlations
between the oncogenes and between the functions of Gene Ontology were also dissected. Two major clusters of oncogenes
and the associated functions were identified: beta-Catenin and Ras signatures which correlated to cell cycle; and TGF-beta,
KRT19, EPCAM which correlated to immune functions. Utilizing the same approach, we also identify a set of GSSs that
differentiates CGC and HCC. 
Conclusion
A unique set of GSSs was identified for cholangiocarcinoma by using S-score method, and this method can be
effectively used to explore novel oncogenic pathways from tumor expression profiling. 
Financial Disclosure (Yidong Chen)
No
FDA Disclosure
Cleared:Yes
Keywords
Signature gene set
gene set enrichment
Cholangiocarcinoma
gene set enrichment
Abstract ID: 267
Mechanism Of STAT3 Folding By The Chaperonin TRiC/CCT
Author List
1. Presenting Author: Wilson Lau
2. Additional Author: Soung-hun Roh
3. Additional Author: Moses Kasembeli
4. Additional Author: Wah Chiu
5. Additional Author: David Tweardy
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The promise envisioned in anticancer drug development with the complete sequencing of the human genome and the
genomes of many cancers has yet to be realized due, in large measure, to our inability to target many oncoproteins with
small, drug-like compounds. Because oncoproteins generally function either as transcription factors or non-enzymatic
signalling proteins through large surface interactions with many downstream biomolecules, they are not amenable to
conventional structure-based, small-molecule inhibitor design. We have recently obtained compelling biochemical and
structural evidence on the interactions between the oncoprotein STAT3 (signal transducer and activator of transcription 3)
and the group II chaperonin TCP-1 Ring Complex (TRiC), the major protein folding machinery exists in eukaryotic cells
(unpublished results). Notably, STAT3 requires the presence of TRiC for its proper function in vivo (unpublished result).
We hypothesize that TRiC contributes critically to the synthesis, folding and function of oncoproteins within cancer cells.
The goal of this project is to characterize the molecular interactions of TRiC with the unstructured region(s) of the nascent,
unfolded STAT3 that binds TRiC en route to acquiring its native conformation. This knowledge can be potentially
exploited as a basis for design of proteostasis modulators to perturb the TRiC-STAT3 interactions for the treatment of a
wide range of cancers. 
Methods
To this end, we will employ biochemical techniques, single-particle electron cryomicroscopy (cryo-EM), crosslinking
tandem mass-spectrometry in conjunction with molecular modelling, to determine a high-resolution structure of the
TRiC-STAT3 complex as well as to identify the discrete sites of interaction between TRiC and STAT3. 
Results
We successfully purified the full-length STAT3 protein and TRiC from bovine testis and demonstrated their binding in
vitro. Using native gel analysis, we also demonstrated that TRiC alone can mediate the refolding of denatured STAT3 in
an ATP-dependent manner. Cryo-EM study of the TRiC-STAT3 pre-folding complex is currently underway.
Conclusion
We anticipate that this knowledge will be useful for evaluating the druggability of the TRiC-STAT3 interaction by
subsequent virtural ligand screening. If successful, the result of this study can open a new possibility of targeting other
oncoprotein folding intermediates by taking advantage of their obligate interactions with TRiC in vivo - a completely novel
approach in structure-based drug design discovery. 
Financial Disclosure (Wilson Lau)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 268
Clinical utility Of MRS measurements of 2-hydroxyglutarate In patients with IDH-mutated gliomas
Author List
1. Presenting Author: Changho Choi
2. Additional Author: Sandeep Ganji
3. Additional Author: Akshay Madan
4. Additional Author: Ralph Deberardinis
5. Additional Author: Bruce Mickey
Poster Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 01:55 PM
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
FFF_SI_2HGmap_I010_I035.jpg
Summary
N/A
Introduction
Accumulation of 2-hydroxyglutarate (2HG) correlates with the presence of mutations in isocitrate dehydrogenase (IDH) 1
and 2 in gliomas. IDH mutations are associated with longer survival compared to IDH wild-type tumors. Thus, there is
intense interest in 2HG as a potential biomarker in all aspects of the management of IDH-mutated gliomas.
Methods
We previously reported the noninvasive detection of 2HG in IDH-mutated gliomas by 1H MR spectroscopy (MRS)
through an IRB-approved research protocol at UT Southwestern (Choi et al. Nat Med 2012). To establish the clinical utility
of 2HG measured by MRS, we report data from 46 patients who had serial scans (range 2-9 scans).
Results
1)2HG levels are stable over time in tumors that have no clinical or radiographic evidence of growth: Twenty patients with
2HG-positive tumors who were followed prior to surgery had at least 2 scans (median follow up 6 months). They were
evaluated for stability of 2HG concentration and for correlation with standard clinical and radiographic parameters used to
monitor disease progression. In non-progressing tumors, 2HG levels were stable within 10% with respect to the mean
values. 2) 2HG levels rise in patients with clinical and/or radiographic evidence of tumor growth: Additional 22 patients
were followed with 2HG imaging after biopsy or completing all treatment in conjunction with regular surveillance MRI
and clinical exam (median follow up time of 2 - 28 months). Eleven of 42 patients had clinical and/or radiographic
progression over the duration of the study, and each was associated with a measureable increase in 2HG levels.
3)Response to treatment with chemotherapy correlates with decreased levels of 2HG: Oligodendrogliomas are highly
responsive to treatment. Four patients with oligodendrogliomas were treated with carmustine (3 patients had 6 cycles, 1
had 3 cycles) and 2HG levels were monitored. In each case, 2HG decreased significantly from pre-treatment levels
(representative patient in Fig. 1).
Conclusion
We have demonstrated the value of MRS monitoring of 2HG levels in the diagnosis, surveillance, and monitoring of
treatment response in patients with IDH-mutated gliomas.
Financial Disclosure (Changho Choi)
No
FDA Disclosure
Cleared:Yes
Keywords
Gliomas
2-Hydroxyglutarate
Magnetic resonance spectroscopy
Mutations of IDH1 and IDH2
Abstract ID: 269
In Vitro And In Vivo Suppression Of The Growth Of Prostate Cancer By miR-200b
Author List
1. Presenting Author: Boyu Zhang
2. Additional Author: Li Zhang
4. Additional Author: Michael Ittmann
5. Additional Author: Li Xin
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
 
We previously found that miR-200b, a miR-200 family member, can inhibit in vitro proliferation of three prostate cancer
cell lines: Du-145, PC3 and LnCap, and that overexpression of miR-200b can suppress AKT-induced prostate
carcinogenesis in a prostate regeneration assay. Since miR-200 family members share similar seed sequences, we sought to
determine whether other miR-200 members also have the potential to suppress the growth of AKT-induced prostate
carcinogenesis in vivo.
Methods
We cloned all five miR-200 family members into an FU-CGW lentiviral vectors separately. Murine prostate epithelial cells
were coinfected with virus expressing AKT and miR-200 family members, mixed with urogenetial sinus mesenchymal
cells, and transplanted under kidney capsules of immunodeficient mice for regeneration.
Results
The regenerated tissues derived from prostate cells infected with miR-200b virus weighed significantly less than those in
other groups. Our results showed that despite that miR-200 family members share similar seed sequences, only miR-200b
can suppresses AKT-induced prostate tumorigenesis in vivo.
Conclusion
This result implicates that miR-200b targets a peculiar group of genes that suppress the mitotic signaling mediated by
AKT.
Financial Disclosure (Boyu Zhang)
No
FDA Disclosure
Cleared:Yes
Keywords
miR-200
prostate cancer
None
None
Abstract ID: 270
Discovery Of Small Molecule Inhibitors Of Gene Expression Utilizing A High Throughput And Multiparameter
Single-cell Approach
Author List
1. Presenting Author: Matthew Sorenson
2. Additional Author: Ashwini Devkota
3. Additional Author: Eun Jeong Cho
4. Additional Author: Scott Stevens
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The control and fidelity of many events in gene expression are important to avoid a tumorigenic state. Tumors often
contain elevated levels of key gene expression factors, which can alter gene expression and all the hallmarks of cancer.
Small molecules that inhibit these gene expression factors are sought after for potential chemotherapeutics. As the need for
additional chemotherapeutics increases, well-designed high throughput approaches will provide novel drugs as well as a
greater understanding of how they work in the cell. To address these needs, we have successfully adapted our yeast gene
expression reporter assay to perform high-throughput screening of small molecules to identify inhibitors of specific gene
expression processes.
Methods
Cells harboring our reporter generate green and red fluorescence from spliced and unspliced transcripts respectively. Cell
populations exhibit a unique signature for genetic defects in many gene expression processes, including transcription,
pre-mRNA splicing, mRNA export and mRNA decay. We completed primary small molecule screens at 10Î¼M by plate
reader analysis. Secondary screens of candidate compounds were performed at 10Î¼M, 1Î¼M and 100nM, and analyzed
by flow cytometry. We use a proprietary analysis platform to compare the fluorescence of compound-treated single cells to
yeast defective in specific gene expression processes. This analysis groups the drug treated and mutant yeast by their
reporter signature, providing vital information on potential target pathways.
Results
To date we have screened thousands of small molecules. Encouragingly, we have identified several compounds that we
believe impinge upon different gene expression processes. Additionally, by virtue of the single-cell nature of our assay, we
have identified molecules that increase cell-to-cell variation in reporter expression. Using our analysis platform we have
identified known drug/target relationships such as 5-FU/Rrp6p as well as shed light on potential mechanisms of action for
several small molecules. We are currently identifying patterns between our primary hit compounds and their effects on our
gene expression reporter.
Conclusion
Our cell-based high throughput assay has enabled us to screen thousands of small molecules for their effect on multiple
gene expression processes. We have identified several molecules of interest that we believe inhibit specific yet unique gene
expression processes. We are currently using genetic and biochemical strategies to elucidate the mechanism of action for
these hits. We are also developing and implementing orthogonal screenings to further characterize hit compounds.
Financial Disclosure (Matthew Sorenson)
No
FDA Disclosure
Cleared:Yes
Keywords
Gene Expression
Inhibitors
High throughput screening
Yeast
Abstract ID: 271
Elucidation Of The Molecular Mechanisms Underlying Ewingâ€™s Sarcoma Sensitivity To DNA Damaging
Agents
Author List
1. Presenting Author: Aparna Gorthi
2. Additional Author: Adam Brown
3. Additional Author: Bishop Alexander
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Ewingâ€™s sarcoma is a rare, yet aggressive and often metastatic pediatric tumor that is thought to be
driven by the oncogenic fusion transcription factor EWS-FLI1. Current treatment regimens for early stage tumors comprise
a systemic polychemotherapy cocktail in conjunction with surgery and/or radiation therapy. Despite a high 5-year survival
rate (~70%), intensity of the highly genotoxic chemotherapy remains a major concern. Patients suffer from severe side
effects such as increased occurrence of secondary tumors, developmental disabilities and chronic illnesses, and the lack of
alternative tumor-specific therapeutic targets poses a major critical barrier to improving treatment efficacy. We hypothesize
that EWS-FLI1 aberrantly regulates the DNA damage response and repair pathways in Ewingâ€™s sarcoma thus
sensitizing them to DNA strand break causing agents.
Methods
We used a panel of 5 Ewingâ€™s sarcoma cell lines including a cell line (A673) where EWS-FLI1 is under the control of a
Tetracycline-repressible promoter, to test the hypothesis that Ewingâ€™s sarcoma cells are exquisitely sensitive to DNA
strand breaks. The primary wild-type fibroblast cell line IMR90, as well as the U2OS pediatric osteosarcoma were used as
controls. The sensitivity of these cells to different kinds of DNA damaging agents (e.g. alkylating agent, topoisomerase
inhibitor, ionizing radiation and PARP inhibitor) was evaluated and compared with control cell lines. PARP activity, DNA
damage (e.g. Î³-H2AX level and 53BP1 focus formation) and DNA repair (e.g. RAD51 focus formation) were monitored.
Results
The Ewing sarcoma cell lines demonstrated nearly over two-fold higher sensitivity to etoposide and MMS as compared to
the control cell lines. They also exhibit significantly higher levels of endogenous Î³-H2AX and RAD51/53BP1 focus
formation. Interestingly, exposure to exogenous damaging agents however, did not result in a concomitant increase in these
signals.
Conclusion
We demonstrate that Ewingâ€™s sarcoma cell lines are significantly more sensitive to agents that cause DNA strand
breaks than control cell lines, and our data suggests that this sensitivity is primarily mediated by EWS-FLI1. The
observation that the markers of DNA damage responses and strand break repair do not increase significantly upon exposure
to exogenous damage suggests a defect in DNA damage response pathways. Furthermore, our results with
etoposide and PARP inhibition point towards the novel discovery of dysregulation of homologous recombination
repair in these tumors. Since this phenomenon seems to be driven by EWS-FLI1, we propose that exploitation of these
defects in Ewingâ€™s sarcoma presents as a much-needed tumor-specific targeted treatment strategy.
Financial Disclosure (Aparna Gorthi)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 272
Neutrophil Elastase In Breast Cancer Cell Lines
Author List
1. Presenting Author: Chun-Hui Su
2. Additional Author: Khandan Keyomarsi
3. Additional Author: Kelly Hunt
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Neutrophil elastase, known as ELA2, is a secretory serine protease with its physiologic role in innate host defense. It is
accumulated and plays a proteolytic role at inflammatory responses. However, excess neutrophil elastase causes abnormal
degradation of extracellular matrix that may lead to metastasis. It has been shown that patients with breast cancer tissues
containing higher levels of neutrophil elastase have poor survival compared to patientsâ€™ tissues with lower levels of
neutrophil elastase. Additionally, elastase cleaves intracellular proteins to produce short forms of cyclin E, CUX1, and
IRS-1 etc., which play important roles in cell proliferation. We therefore hypothesize that neutrophil elastase is a
therapeutic target and inhibition of neutrophil elastase can be used as a targeted therapy in treatment of metastatic breast
cancers.
Methods
Activity of pure elastase is evaluated using a colorimetric assay with the substrate, Suc-Ala-Ala-Pro-Val-p-nitroanilide and
the elastase activity is inhibited when incubated with elastase inhibitors.
Results
The assay is further applied in an elastase knockdown cell line (MDA-MB-231) and this cell line shows lower elastase
activity than the empty vector control. An endogenous elastase inhibitor, elafin, is knockdown in the 76NF2V cell line and
this cell line shows higher elastase activity than the control. These results confirm that our assay can successfully detect
intracellular elastase activity for future screening in various breast cancer cell lines.
Conclusion
We have initially identified that BT549 and MDA-MB-157 cell lines have higher elastase activity than MDA-MB-436 and
MDA-MB-468. The mechanism and the signaling pathway of elastase-involved metastasis will also be investigated to
identify more potential targets for cancer therapy.
Financial Disclosure (Chun-Hui Su)
No
FDA Disclosure
Cleared:Yes
Keywords
neutrophil elastase
metastasis
breast cancer
protease
Abstract ID: 273
Controlled Manipulation Of Akt Signaling In Dendritic Cells To Enhance Efficacy Of Dendritic Cell Vaccine For
Cancer
Author List
1. Presenting Author: Matthew Collinson-Pautz
2. Additional Author: Indira Vedula
3. Additional Author: Matthew Halpert
4. Additional Author: Vanaja Konduri
5. Additional Author: Jonathan Levitt
6. Additional Author: David Spencer
7. Additional Author: William Decker
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Introduction: Dendritic cells (DCs) exist as a crucial node of the immune network serving to integrate and conduct
immunological signals in the microenvironment from the innate to adaptive arms of the immune system. This critical role
for DCs in the immune system bestows them with the potential to be potent tools in the fight against cancer. Akt1 is a
critical regulator of both innate and adaptive immune-signal mediated DC survival and activation via modulation of Bcl2.
As such, Akt1 is an exciting target for enhancing DC potency in Th1 polarizing vaccine applications. Previously, our lab
has developed both constitutively active as well as drug-inducible Akt (iAkt) alleles that were capable of recapitulating
endogenous Akt signaling. Control of iAkt inducibility is achieved by transiently crosslinking a lipid raft targeted protein
to a chimeric Akt protein through FKBP and FRB regions, respectively, in the presence of a heterodimer drug (CID).
Therefore, we sought to further mature iAkt technology for use in DC cancer vaccines.
Methods
Methods: Using standard molecular cloning methods we constructed four different inducible Akt expression constructs to
test for expression and functionality in order to determine the optimal allele to use in a vaccine. Comparison was performed
utilizing an NFÎºB SEAP reporter assay in Jurkat Tag cells. After the determination of the optimal iAkt allele, functionality
was further characterized by Western blot of down-stream Akt activation markers. Furthermore, the chosen iAkt
expression cassette was packaged into an adenoviral expression vector (AdV) to transduce DCs for vaccine production.
Results
Results: Following the comparison of the available inducible Akt alleles we determined that the optimized iAkt is the FIAb
construct. FIAb contains a poliovirus IRES site to permit expression of both protein components of the iAkt. FIAb was
able to readily induce phosphorylation of Akt in the presence of CID.
Conclusion
Conclusions: Based on the present data we have identified an optimized iAkt, FIAb, to be used to enhance DC cancer
vaccines. FIAb is capable of modulating Akt downstream signaling in a CID dependent manner permitting spatial and
temporal control of Akt activation within cells. Therefore, we can move forward to adapt this technology for cancer
vaccine applications.
Financial Disclosure (Matthew Collinson-Pautz)
No
FDA Disclosure
Cleared:Yes
Keywords
dendritic cell
Akt signaling
vaccine immunotherapy
translational medicine
Abstract ID: 274
Synthetic And Viral Nanoparticle Reporters For The Ultrasensitive Detection Of Cancer Biomarkers
Author List
1. Additional Author: Julia Litvinov
2. Presenting Author: Ulrich Strych
3. Additional Author: Meenu Adhikari
4. Additional Author: Sagar Dhamane
5. Additional Author: Anna Hagstrom
6. Additional Author: Katerina Kourentzi
7. Additional Author: Federico Monzon
8. Additional Author: Richard Willson
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Early detection of cancer is correlated with a significantly better outcome for patients, and several studies have reported the
ability to distinguish cancer from normal tissue based on specific protein markers. Here, we aim to develop and evaluate
novel nano- and immuno-phage particles for the multiplexable, high-specificity detection of very low levels of cancer
diagnostic markers in serum and bronchoalveolar lavage (BAL) samples.
Methods
Cancer biomarkers (Vascular Endothelial Growth Factor (VEGF) and Folate Receptor-alpha (FR-alpha)) were spiked into
buffer, commercially-acquired serum and banked BAL specimens at concentrations ranging from nM to sub-fM. Magnetic
particles were functionalized with antibodies (or folate, in case of Folate Receptor detection) to capture their corresponding
antigens in serum or BAL. After concentrating, and washing the particles using a permanent magnet, synthetic and viral
nanoparticle reporters were added to detect the captured antigen. The phage particles are engineered to express a small
biotinylatable peptide that allows the convenient streptavidin-based attachment of any biotinylated affinity agent, including
full-length antibodies without the need for cloning. In addition, different phage populations can be engineered to contain
multiple (>20) copies of unique reporter sequences which are detected by real-time PCR, allowing multiplexing and
yielding improved sensitivity. For comparison to an established technology, ELISAs were performed using standard
techniques/reagents.
Results
We have shown a concentration-dependent response of our assay platform to various amounts of our model cancer
biomarkers. VEGF was detected in phosphate buffered saline at sub-femtomolar, and in BAL fluid at picomolar
concentrations. Preliminary experiments show FR-alpha detection in buffer at low picomolar concentrations. Non-specific
binding of phages was significantly lower than observed with particle-based assays.
Conclusion
The project presented here constitutes a novel, highly sensitive detection system. In its final version, the proposed
technology will utilize a panel of cancer protein biomarkers (instead of only one or two markers), which may improve
specificity, and the immuno-phage technology may increase sensitivity. The successful development of the technology will
set the stage for a diagnostic assay for the early detection of cancer. The test could then be used to determine which
patients need to subsequently undergo more expensive and/or invasive procedures.ï¿½
Financial Disclosure (Ulrich Strych)
No
FDA Disclosure
Cleared:Yes
Keywords
immuno-phage particles
biomarkers
lung cancer
ovarian cancer
Abstract ID: 275
A Variable Repetition-Time Protocol For Collection Of Hyperpolarized MRI Data Uncovers Strong Correlations
With In Vivo Cancer Metabolism
Author List
1. Presenting Author: Matthew Merritt
2. Additional Author: Crystal Harrison
3. Additional Author: Chendong Yang
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
fig_correlations.jpg
Summary
Introduction
Hyperpolarized 13C (HP) is rapidly achieving popularity as a method to monitor metabolism in live tissues.
Typically, [1-13C]pyruvate has been the most popular substrate due to its central importance in metabolism
and its long T1. The standard method to image HP substrates is to use a small excitation angle and a constant
repetition time (Tr). However, a comparison of the metabolic information content between different data collection
methods has not been explored. Here we compare constant Tr with a new variable Tr protocol in a murine model of cancer.
Methods
SF188 glioblastoma cells were subcutaneously implanted and tumors were allowed to reach 10-20 mm in diameter.
[1-13C]pyruvic acid was hyperpolarized at 1.2 K in a 4.7 T DNP polarizer. The polarized sample was
dissolved using 4 mL of sodium-bicarbonate, filtered, and injected (300 Î¼L) into mice via a jugular catheter.
13C spectra were acquired using a 4.7 T Agilent scanner and a 2 cm diameter surface coil with slice selective
pulses through the tumor. HP data was collected on each tumor using a constant Tr (30Â° pulses) and variable, increasing
Tr (90Â° pulses). Each tumor was then excised for biochemical analysis.
Results
Following injection of HP [1-13C]pyruvate, the HP [1-13C]lactate signal appears rapidly,
reaches maximum intensity, then relaxes back to zero. The signals of HP pyruvate and HP lactate were typically larger
using the constant Tr protocol and a significant correlation was found between the tumor volume and the total carbon
signal with this method. This was not observed when using the variable Tr protocol. Rather, strong correlations were found
between several NMR measurements and the concentration of LDH in the extracted tumors (Figure 1). Metabolite
concentrations were also measured, but no significant correlations were found using either protocol.
Conclusion
While the constant Tr approach provides greater signal-to-noise, little additional insights into tumor metabolism was found
using this standard method. In contrast, the new variable Tr method showed strong correlations between a variety of HP
parameters and the activity of LDH, an enzyme regulated by a number of oncogenes. Figure 1A shows a correlation
between enzymatic LDH activity and the lactate/pyruvate ratio at the time-point of maximum lactate, a previously reported
measure of LDH. Therefore, different protocols exert significant effects on the output and interpretation of HP signals, thus
sampling schemes should be carefully chosen to optimize the measurement of a desired metabolic parameter.
Financial Disclosure (Matthew Merritt)
No
FDA Disclosure
Cleared:Yes
Keywords
hyperpolarization
pyruvate
glioblastoma
MRI
Abstract ID: 276
Preparation Of A Clinical Grade Co-ArgI-PEG For Arginine Deprivation Therapy
Author List
1. Presenting Author: Jung-Hee Woo
2. Additional Author: Zhenyu Li
3. Additional Author: Soo Kang
4. Additional Author: Shi-Yan Li
5. Additional Author: Yizhen Liu
6. Additional Author: Leodis Gupton
7. Additional Author: Arthur Frankel
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Certain human cancers are auxotrophic for the non-essential amino acid L-arginine. Arginine auxotrophy has been
observed in various cancers Arginine deprivation by bacterial arginine deiminase has demonstrated anti-tumor activity in
animal models and clinical trials but its immunogenicity hampered long-term treatment. To overcome this, PEGylated
human arginase I with substituted cobalt ions (Co-ArgI-PEG) has been developed. Co-ArgI-PEG showed anti-tumor
activity in vitro and in vivo models. In this study, a clinical grade Co-ArgI-PEG drug substance
was produced in GMP compliance for testing in humans. Characterization of the drug substance is ongoing.
Methods
For manufacture of Co-ArgI-PEG acceptable for use in phase I clinical trials, a GMP production process was developed.
Production of the active drug substance, Co-ArgI-PEG, consists of three phases: expression of human arginase I (hArgI)
from a genetically modified Escherichia coli strain in a 40-L fermentor, purification of hArgI, and PEGylation/cobalt
replacement of hArgI to yield Co-ArgI-PEG. The final material was filter-sterilized, and stored at -80oC.
Analytical assays are being developed for characterization of the drug substance.
Results
Cell banks of an E. coli expression strain expressing hArgI were prepared and tested for microbial purity, viability,
kanamycin-resistant cell counts and microbial identity. Using the cell bank, three batches of 32-L scale E. coli fermentation
were performed. An average expression level of hArgI in E. coli was 3.70g/L and a total of 367.0g of crude ArgI was
obtained. The harvest from each 32-L scale fermentation was pelleted and divided into six portions for purification of ArgI.
The purification procedure comprised cell disruption, a SP capture step, a Q/SP concentration step, and a Superdex GF
polishing step. ArgI intermediate material had high purity of >98.0% and low impurity levels. For PEGylation, the
concentration of purified ArgI was adjusted to 7-12mg/mL and incubated with a 20 molar excess PEGylation agent (MW
5000) at 25oC for 60 min. The PEGylation reaction was terminated by adding glycine. After termination of
PEGylation reaction, 0.2M CoCl2 was added to a final concentration of 10mM and the solution incubated at
50oC for 20 min in order to replace the manganese ions of Mn-ArgI-PEG as cofactors with cobalt ions. Then
the drug substance, Co-ArgI-PEG was further purified by gel filtration column. The Co-ArgI-PEG peak was collected, and
sterile-filtered.
Conclusion
A total of 160g of Co-ArgI-PEG was produced. In order to confirm quality of the drug substance, process impurity assays
for IPTG, kanamycin and free PEG molecules are being developed.
Financial Disclosure (Jung-Hee Woo)
No
FDA Disclosure
Cleared:Yes
Keywords
Arginine deprivation
Arginase I
PEGylation
None
Abstract ID: 278
Predictors Of Quality Of Life Changes Following Chemotherapy In Patients With Advanced Non-small Cell Lung
Cancer
Author List
1. Additional Author: Shirin Shallwani
3. Additional Author: Jadranka Spahija
4. Additional Author: Goulnar Kasymjanova
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Lung cancer is the leading cause of cancer-related death in both men and women worldwide, with the highest rates in
North America and Europe.Due to the poor prognosis associated with lung cancer and the toxicities of its medical
treatment, a priority of research in lung cancer is concerned with not only improving survival but also improving
health-related quality of life during that survival. 
This study aimed to identify predictors of change in physical and mental components of health-related quality of life
(HRQOL) following two chemotherapy cycles in patients with advanced non-small cell lung cancer (NSCLC).
Methods
A retrospective analysis study of 24 men and 23 women with newly diagnosed advanced NSCLC receiving two cycles of
first-line chemotherapy was performed. Primary outcomes were change in the physical and mental components of
HRQOL (physical and mental component summaries (PCS and MCS) of the 36-item Short-Form Health Survey).
Predictors were pre-chemotherapy patient-reported symptoms (Schwartz Cancer Fatigue Scale (SCFS), and Lung Cancer
Subscale), nutritional screening (Patient-Generated Subjective Global Assessment) and physical performance (6-Minute
Walk Test (6MWT), one-minute chair rise test and grip strength).
Results
Multiple linear regression modelling showed that pre-chemotherapy SCFS score and 6MWT distance were the strongest
predictors of change in mental HRQOL accounting for 13% and 9% of the variance, respectively. No significant predictors
were found for change in physical HRQOL.
Conclusion
Fatigue and physical performance predict change in mental HRQOL following chemotherapy in patients with advanced
NSCLC. Clinical management of these factors may be useful for HRQOL optimization in patients with advanced NSCLC
undergoing chemotherapy.
Financial Disclosure (Jung-Hee Woo)
No
FDA Disclosure
Cleared:Yes
Keywords
Lung Cancer
Quality of Life
Prediction of outcome
Physical Function
Abstract ID: 279
Gene Variants As Predictors Of Cancer-Acquired Lymphedema Determined From Next Generation Sequencing
And NIRF Lymphatic Imaging
Author List
1. Additional Author: Manuel Gonzalez-Garay
2. Additional Author: Germain Agollah
5. Additional Author: Melissa Aldrich
6. Additional Author: Chinmay Darne
8. Additional Author: Renie Guilliod
10. Presenting Author: Eva Sevick-Muraca
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Lymphedema is a clinical manifestation that arises from structural and functional defects in the lymphatic vasculature
which, upon being overwhelmed with excess blood capillary filtration, results in irresolvable, progressive edema that can
lead to disfigurement. Primary lymphedema is rare and associated as a monogenetic disease arising from mutations in one
of six known genes with variable penetrance and expressivity. The majority of primary lymphedema patients do not harbor
any of these mutations. Acquired lymphedema commonly arises as a treatment complication in cancer survivors, and the
hypothesis that there is a genetic predisposition remains untested. Candidate gene studies involving single individuals
suggest that HGF and c-MET mutations are responsible for a very small minority of primary as well as acquired (breast
cancer related) lymphedema cases, but variable penetrance and expressivity remain unexplained.
Methods
The protocol used for this study (NCT00833599) was approved by the FDA under a combinational investigational new
drug application for the investigational technique of near-infrared fluorescence lymphatic imaging (NIRFLI) and approved
by the UTHSC-H IRB. In this study, we employed NIRFLI to phenotype symptomatic and asymptomatic members of a
large family presenting with primary lymphedema and with acquired lymphedema. We employed unbiased whole exome
sequencing (WES), and cosegregation analyses to evaluate germ-line protein encoding SNPs and large insertions or
deletions that could be directly attributed to an NIRFLI phenotype of aberrant lymphatics. Causal mutations predicted from
WES analyses were confirmed from Sanger sequencing and biological validation studies conducted on primary and
telomerase-immortalized lymphatic endothelial cells (LECs).
Results
We found that gene variants encoding for (i) a relatively unknown phosphatase that is an adaptor protein to receptor
tyrosine kinase (RTK) c-MET and for (ii) HGF, the ligand to c-MET, could explain the varied expressivity of disease. In
an unrelated mother and daughter pair, we found a shared damaging mutation in FTL4 that, when compounded by a
damaging mutation in the same phosphatase in the mother, resulted in the most severe lymphatic phenotype with earlier
onset of symptoms than seen in the daughter. siRNA knock-down of the phosphatase in LECs showed reduced
tubulogenesis, migration, adhesion to ECM substrates, and proliferation upon stimulation with HGF and VEGFC (ligand to
FLT4). Immunoblotting and immunoprecitation confirmed association of the phosphatase with both RTKs.
Conclusion
Using the combination of accurate phenotyping, unbiased WES of primary and acquired lymphedema in family members,
we confirmed that a predisposing genetic condition for the condition could exist.
Financial Disclosure (Eva Sevick-Muraca)
No
FDA Disclosure
Cleared:Yes
Keywords
cancer acquired lymphedema
survivorship
genetic predisposition
near-infrared fluroescence imaging
Abstract ID: 280
Ultrasensitive Magnetic Sensors: Clinical Collaborators Invited
Author List
1. Presenting Author: Richard Willson
2. Additional Author: Yu-Chi Liang
3. Additional Author: Archana Kar
4. Additional Author: Binh Vu
5. Additional Author: Katerina Kourentzi
6. Additional Author: Long Chang
7. Additional Author: Dmitri Litvinov
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
We are developing an ultra-sensitive magnetic detector for measuring proteins and nucleic acids in small clinical samples
such as FNAB and FFPE specimens and rare species in blood, urine, and broncho-alveolar lavage fluid. Successful early
proof-of-concept has been funded by NSF, and by an NIH RC1 â€œChallengeâ€• grant. When fully implemented the
detector array will be cheap enough to be disposable (like a low-capacity USB drive), massively parallel (thousands of
individual sensors) and capable of detecting single 60 nm magnetic particles. Particles of this size can be bound by single
100 pN antibody or hybridization interactions, raising the prospect of detecting single protein, DNA, or RNA molecules
(though diagnosis would be based on ROC analysis of multiple binding events).
Methods
A Co/Cu/Co/NiFe spin-valve design with a bottom Co layer pinned by a Co/Ru/Co synthetic antiferromagnetic tri-layer
was employed. The Ta/Ru/Co/Ru/Co/Cu/Co/NiFe/Ta multilayer stack was deposited using magnetron sputtering with an
external magnetic biasing field applied during deposition to magnetically bias a Ni81Fe19 layer
(to control the magnetic properties of the free (top) Co layer in the spin-valve). The deposition conditions and thicknesses
of individual layers were carefully optimized to maximize the GMR ratio (13% in non-patterned films). Nano-scale
GMR-based biosensors were achieved using a combination of optical (for leads) and e-beam (for sensors) lithography.
Poly(4-hydroxystyrene) (PHOST) was used as a negative e-beam resist. A poly(methylglutarimide) (PMGI) undercut layer
was used to achieve efficient lift-off. Twelve-sensor arrays comprised of 400nm-long sensors with the width varying
between 200nm and 400nm were built. The entire sensing area was overcoated with pin-hole free conformal 25nm
aluminum oxide to protect against corrosion by salty biological fluids.
Results
GMR peaks corresponding to antiparallel magnetization configuration over a baseline corresponding to parallel
magnetization configuration of the Co layer in the spin-valve stack have been observed; a monolayer of 50nm
Fe3O4 nanoparticles deposited over a sensor surface results in a very significant shift of the
position of the GMR peak, supporting the expectation of extreme sensitivity.
Conclusion
We have proof-of-concept of an extremely sensitive detection technology, broadly applicable to detection of biomarkers,
indicators of therapy effectiveness, and disease recurrence. We invite the collaboration of researchers with access to human
samples relevant to developing clinically-actionable diagnostics enabled by extremely sensitive detection.
Financial Disclosure (Richard Willson)
FDA Disclosure
Cleared:Yes
Keywords
GMR sensor
biomarkers
diagnostics
magnetic nanoparticles
Abstract ID: 281
Access To Cancer Care For Low-Income And Uninsured Patients
Author List
1. Presenting Author: Carolyn Bernard
2. Additional Author: Melissa Mims
3. Additional Author: Rosalind Bello
4. Additional Author: Lewis Foxhall
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Texas Cancer Information (TCI) is a web-based cancer information resource funded by MD Anderson Cancer Center. TCI
maintains numerous databases related to cancer providers, facilities, community resources and statistics related to cancer.
TCIâ€™s Access to Cancer Care for Low-Income and Uninsured Patients database at
http://www.texascancer.info/access is intended to reach low-income, uninsured Texans seeking free or low-cost local
cancer screening or treatment. Information on how to obtain cancer care services in all Texas counties is now available in
English and Spanish. Social workers or volunteer organizations can also print this information to give to their clients. 
Methods
TCI and the TCI Advisory Committee, which is made up of representatives of cancer-related and community-based
agencies, determined that TCI should work to fill an important information gap that impacts cancer patients and their
families. That is, how low-income Texans without insurance receive cancer screening and treatment. TCI investigated
procedures, contacts and clinic locations in each Texas county. The results of this study are incorporated in web-based
documents on the TCI website. These are presented as Access to Care documents that were designed in a
simple, question and answer format and written at a seventh grade reading level. The documents have also been translated
into Spanish. TCI recently created an interactive, searchable version of the database in English and Spanish and pilot tested
it with nurses and social workers before launching it in July 2012. 
Results
Access to Care is one of the most utilized databases on the TCI website. However, many individuals who can
benefit from the access information cannot or choose not to use the Internet. Interactions with professional and public users
of the tool led to the concept of developing an online training program for nurses and social workers, particularly those in
rural and underserved areas and areas with large Spanish-speaking populations, regarding how to find services for their
low-income and uninsured patients. The Continuing Education program, funded by the Cancer Prevention and Research
Institute of Texas, was launched in July 2012, along with the enhanced interactive Access database. 
Conclusion
A preliminary review of utilization of the Access database, before and after the launch of the interactive
version and CE program, supports the concept that there is a significant need for this type of information. Next steps
include raising awareness of the tool throughout the state, determining if there is additional information that should be
included and evaluating the impact of the resource. 
Financial Disclosure (Carolyn Bernard)
No
FDA Disclosure
Cleared:Yes
Keywords
Access
Uninsured
Low-Income
Local Services
Abstract ID: 282
Inhibition Of DNA Repair As A Therapeutic Strategy In Glioblastoma Multiforme
Author List
1. Additional Author: Carlos Gil Del Alcazar
2. Additional Author: Molly Gillam
3. Additional Author: Xiaohuan Gao
4. Additional Author: Nozomi Tomimatsu
5. Additional Author: Bipasha Mukherjee
7. Presenting Author: Sandeep Burma
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Glioblastoma Multiforme (GBM) are incurable brain tumors. Surgical resection followed by radiotherapy is the mainstay
of treatment. However, these tumors are highly radioresistant and always recur quickly. The only significant advance in
treatment of GBM in the past few decades was the use of Temozolomide (TMZ) in conjunction with ionizing radiation (IR)
which modestly increases the median survival of patients from 12 to 14 months. Therefore, new treatment modalities are
urgently needed in order to further sensitize these tumors and improve survival.
Methods
Inhibition of the DNA-damage response (DDR) has been proposed as a strategy to sensitize tumors to radiation, and
numerous compounds that are able to inhibit key DDR enzymes are being developed as radiosensitizers. However, most of
the available compounds do not show therapeutic bioavailability in tissues and/or fail to cross the blood-brain barrier. In
this study, we characterized NVP-BEZ235, originally identified as a dual PI3K/mTOR inhibitor, as a potent inhibitor of
ATM and DNA-PKcs kinases.
Results
We found that only nanomolar concentrations of NVP-BEZ235 could significantly inhibit IR-induced ATM and
DNA-PKcs activation.Using specific non-homologous end-joining and homologous recombination assays, we showed that
both double strand break (DSB) repair processes are abrogated in the treated cells. Thus, NVP-BEZ235 radiosensitized a
panel of glioma lines to a greater extent than the most potent available inhibitors of ATM and DNA-PKcs. To test the
efficacy of the drug in vivo, we generated subcutaneous tumors using the highly radioresistant human glioma line U87
overexpressing EGFRvIII. We observed that NVP-BEZ235 could impair DSB repair in these tumors as quantified by
immunostaining for 53BP1 foci. U87-VIII tumors are exceptionally radioresistant; however combinatorial treatment with
NVP-BEZ235 and IR resulted in dramatic tumor regression. We have shown previously that TMZ induces
replication-associated DSBs raising the possibility that NVP-BEZ235 might also sensitize tumors to chemotherapy with
TMZ. Upon treating a cohort of tumor-bearing mice with both NVP-BEZ235 and TMZ, we observed that NVP-BEZ235
could enhance the effectiveness of TMZ. Additionally, we determined that NVP-BEZ235 is able to cross the blood brain
barrier as it can inhibit the phosphorylation of S6, a downstream substrate of Akt, in the brain.
Conclusion
In sum, these results have important implications for the potential utility of NVP-BEZ235 as a clinical radio- or
chemo-sensitizer for the treatment of GBM with IR or TMZ.
Financial Disclosure (Sandeep Burma)
No
FDA Disclosure
Cleared:Yes
Keywords
Glioblastoma
DNA-PKcs
ATM
NVP-BEZ235
Abstract ID: 283
Texas Screening Alliance For Cancer Therapeutics (TxSACT)
Author List
1. Additional Author: Clifford Stephan
2. Additional Author: Geoffrey Bartholomeusz
3. Additional Author: Kevin Dalby
4. Presenting Author: Peter Davies
5. Additional Author: Michael Mancini
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The Texas Screening Alliance for Cancer Therapeutics (TxSACT) is a component of the John S. Dunn Gulf Coast
Chemical Genomics Consortium funded by a MIRA grant from CPRIT to provide statewide access to state-of-the-art
high-throughput screening resources for Texasâ€™ cancer researchers. This Alliance of six academic institutions (Texas
A&M HSC, UT-M.D. Anderson Cancer Center, UT-Austin, Rice University, Baylor College of Medicine and the
Methodist Hospital Research Institute) builds upon the infrastructure and personnel assembled by the Gulf Coast
Consortium (GCC) to provide high-throughput screening resources to its investigators, expanding the scale and the scope
of the GCC program, to address the needs of cancer researchers throughout Texas. The program has implemented a new
state-of-the-art imaging-based high-throughput imaging-based screening program based upon the InCell6000 confocal
imaging platform.
Methods
The primary goal of TxSACT is to accelerate the movement of basic discoveries in cancer research into clinical application
through provision of critical resources to support drug discovery research and therapeutics development in Texas. The
Alliance includes three â€œDiscovery Programsâ€•--- the chemistry â€“ based New Drug Discovery Program, the
pharmacology â€“ based Combinatorial Drug Discovery Program and the molecular biology â€“ based Therapeutic Targets
Discovery Program. These programs are designed to support the full range of experimental approaches being used by
Texasâ€™s cancer researchers to address the challenge of developing new treatments for cancer. TxACT includes two
technology cores, the Bioinformatics Core, which provides advanced, systematic approaches for better experimental
design, integration and interpretation of screening readouts, and the Educational and Information Exchange Core, which
support key requirements common to multiple components of the program.
Results
In the last two years, the Chemical Genomics Consortium has completed over 50 screening projects, including numerous
RNAi screens for target identification and validation, several screens using off-patent drug collections for drug
repositioning and combinatorial therapy, targeted therapeutics using current clinical candidates and several screens for new
chemical leads discovery.
Conclusion
The expansion of the GCCâ€™s research program to support all aspects of cancer-related drug discovery research in Texas
will place into the hands of our Stateâ€™s researchers critical tools needed to translate discoveries into new therapies for
cancer.
Financial Disclosure (Peter Davies)
No
FDA Disclosure
Cleared:Yes
Keywords
discovery programs
state of the art
InCell6000
None
Abstract ID: 284
Design Of A Mobile-Enabled Web Application To Promote Physical Activity For Older Cancer Survivors: Results
From Mixed-Method Formative Research
Author List
1. Presenting Author: Yan Hong
2. Additional Author: Deborah Vollmer Dahlke
4. Additional Author: Angie Hochhalter
5. Additional Author: Jana Reynolds
6. Additional Author: Ninfa PeÃ±a Purcell
7. Additional Author: Gabriel Laguillo
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
ipad safari Main Screen.jpg
Summary
Introduction
The benefits of physical activity (PA) for cancer survivors are well documented. However, few older cancer survivors
(OCS) are engaged in regular PA. With the increased use of mobile technologies among older adults, such technologies
may be an effective method to deliver PA promotion program for OCS. The objective of this study was to collect
information to design and evaluate the content and structure for an OCS-friendly PA-promotion web application.
Methods
Mixed methods encompassing group discussions, individual interviews and brief surveys with community leaders, OCS,
cancer care providers, and software professionals were used in formative research.
Results
The stakeholders commented on the feasibility of a mobile solution for health promotion in OCS, provided guidance on
barriers to regular PA and corresponding solutions, suggested key functions of the web application and strategies for
evaluation. Their feedback and suggestions were incorporated into the development of â€œICANFITâ€•, a mobile-enabled
web application, designed specifically for OCS.
Conclusion
It is critical that stakeholders of the target users be included in the design of the mobile application and its evaluation, so
that the program is relevant, appealing and addresses needs of target users.
Financial Disclosure (Yan Hong)
No
FDA Disclosure
Cleared:Yes
Keywords
Older cancer survivors
Physical activity
Survivorship
Mobile Solution
Abstract ID: 285
A Novel Druggable Oncogenic Feedback Loop In Neuroblastoma
Author List
1. Presenting Author: Yihui Fan
2. Additional Author: Jianhua Yang
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 02:30 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Neuroblastoma (NB) is the most common extracranial malignant solid tumor with high lethality in children. Ubiquitin
mediated degradation, which can be reversed by deubiquitinase (DUBs), plays a pivotal role in protein homeostasis and is
critical in cancer-related cellular processes. MYCN, a short-lived protein targeted for ubiquitin-mediated degradation in
normal neuronal cells, is stabilized in NB. Therefore, it is highly likely that an overexpressed DUB is involved in the
deubiquitination of MYCN to prevent its degradation and promote its oncogenic activity.
Methods
To identify the potential DUBs of MYCN in NB, we generated a library of mammalian expression vectors that encode 38
members of Ubiquitin Specific Peptidase (USP) subfamily of DUB. Cell proliferation assay, colony formation assay, WB,
Real-time PCR, Luciferase reporter assay and Immunoprecipitation were used.
Results
Using a functional genomics screen, we found that USP14 upregulates both MYCN and MYC transcriptional activity.
USP14 enzymatic activity is required for its role on MYCN, as deuibiquitinase-deficient C114A mutant failed to
upregulate MYCN/MYC transcriptional activity. Overexpression of USP14 wildtype but not deuibiquitinase-deficient
C114A mutant deubiquitinates MYCN/MYC and stabilize MYCN/MYC. Knockdown USP14 expression reduced
MYCN/MYC protein level and inhibited NB cell proliferation and colony formation. Interestingly, bioinformation and
micro-array analysis predicts that USP14 is a MYCN transcriptional target. Doxycycline induces USP14 expression in a
MYCN-inducible SHEP cell line, but not in control SHEP cells. Importantly, overexpression of USP14 correlates with a
poor patient outcome in a cDNA microarray analysis of primary NB tissue. A novel USP14 inhibitor (IU1) inhibits NB
cells proliferation and reduces MYCN/MYC level. More significantly, USP14 inhibition overcomes the chemotherapeutic
resistance in chemotherapeutic resistant NB cell line LA-N-6.
Conclusion
Together, we provide evidence that MYCN amplification and/or overexpression upregulate USP14 expression and USP14
in turn stabilizes MYCN and promotes MYCN transcriptional activity and oncogenic function by deubiquitinating MYCN
and preventing its proteasome-mediated degradation in NB. Therefore, USP14 is a potential therapeutic target in NB.
Financial Disclosure (Yihui Fan)
No
FDA Disclosure
Cleared:Yes
Keywords
USP14
MYCN
Deubiquitination
Chemotherapy
Abstract ID: 286
Physician Follow-up And Guideline Adherence In Post-Treatment Surveillance Of Colorectal Cancer In Texas
Author List
1. Presenting Author: Gabriela Vargas
3. Additional Author: Abhishek Parmar
5. Additional Author: Kimberly Brown
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Current guidelines for post-resection surveillance of colorectal cancer uniformly recommend history and physical exam,
carcinoembryonic antigen (CEA) testing, and colonoscopy. No consistent guidelines exist for the use of abdominal
computed tomography (CT) and positron emission tomography (PET/PET CT). The goal of our study was to describe
current trends, the impact of oncologic follow-up in adherence to guidelines and patterns of use of non-recommended tests.
Methods
We used Texas Cancer Registry-Medicare linked data (2001-2006) to identify physician visits, CEA testing, colonoscopy,
abdominal CT, and PET/PET CT scans in patients 66 and older with stage I-III colorectal cancer who underwent curative
resection. Adherence to guidelines was assessed with a composite measure of physician visits (>2 per year x 3 years), CEA
tests (>2 per year x 2 years), and colonoscopy use (>1 in three years) from start of surveillance (90 days after surgery).
Results
In patients who survived 3 years (N=8080), the overall adherence to guidelines was 25.1%. 85.4% had physician visits,
29.5% had CEA testing, and 75.3% had colonoscopy as defined above. 57.5% of patients saw a medical oncologist and
38.2% saw a medical oncologist at least once a year for the 3 years. In patients seen by a medical oncologist after surgery,
adherence to guidelines increased to 41.6%. It improved to 56.7% in those who saw a medical oncologist at least once a
year. For those who did not see a medical oncologist, guideline adherence was only 2.9% (P<0.0001). For those with
regular medical oncology visits, 48.6% met CEA recommendations, and 83.1% met colonoscopy recommendations. While
guideline adherence remained fairly constant, the use of abdominal CT and PET/PET CT increased from 57.5% and 9.5%,
respectively, for patients diagnosed in 2001 to 65.8% and 24.6% (P<0.0001) for patients diagnosed in 2006 Patients who
saw a medical oncologist were more likely to get abdominal CT (79.1% vs. 41.0%, P<0.0001) and PET/PET CT (30.5%
vs. 3.5%, P<0.0001) than those who did not.
Conclusion
Overall compliance with current minimum guidelines for post-treatment surveillance of colorectal cancer remains low and
the use of non-recommended testing has increased over time. Adherence to guidelines and use of non-recommended tests
are markedly increased in patients who have regular follow-up by a medical oncologist. Improved awareness of
recommendations among providers following colorectal cancer patients may improve adherence to current guidelines. The
comparative effectiveness of CT and PET/PET CT in the surveillance of colorectal cancer patients needs further
examination.
Financial Disclosure (Gabriela Vargas)
No
FDA Disclosure
Cleared:Yes
Keywords
cancer care
post-treatment surveillance
physician follow-up
colorectal cancer
Abstract ID: 287
AYA Healthy Survivorship iPhone Application For Self-Reported Assessments And Survivorship Plans
Author List
1. Presenting Author: Deborah Vollmer Dahlke
3. Additional Author: Yan Hong
4. Additional Author: Christopher Hamilton
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
assessment screen_final.jpg
Summary
Introduction
â€œAYA Healthy Survivorshipâ€• is a system made up of two elements: a mobile application (iPhone app) and a
companion website (www.healthysurviviorship.org). AYA Healthy Survivorshipâ€™s purpose is to provide Adolescent
and Young Adult (AYA) cancer survivors ages 15-39 with a way to assess their quality of life and health in light of their
cancer survivorship by assessing their responses to specific questions. App users receive a personalized Healthy
Survivorship score, which includes BMI, and suggestions or tips for improvement. The scores are tracked and users may
re-enter new data. Information on screening for AYA cancer survivors and links to the Childrenâ€™s Oncology Group
â€œHealth Linksâ€• information on late effects is available via the app. App users can agree to receive daily tips for
improvements in diet and lifestyle participation via their iPhones. Opportunities for social media and networking via tools
like Twitter, Chatter, and Facebook are offered. Users who register on the HIPAA compliant and secure Healthy
Survivorship website are offered information on survivorship research and clinical trials, healthy recipes and survivorship
plans templates. 
Methods
The app self assessment system was developed through multiple iterative live meetings, surveys, and webinars with
individual cancer survivors, oncologists, cancer advocates and AYA/Childhood Cancer researchers. This process allowed
the team to review validated survey questions and models. We also conducted preliminary feasibility and usability reviews
of the look and feel of both the app views and icons, the website interface and cancer specific survivorship plan templates.
The app was â€œsoft launchedâ€• in its beta form on the Apple App Store and its availability communicated only
moderately.
Results
The beta iPhone app has had 236 downloads from the app store during the 3 month pilot period. Of those users, 178 or
75% are using the self-assessment tool and the average user takes the self-assessment 1.92 times. Of all app users, only 21
(9%) have initiated survivorship care plans. However, only templates for thyroid and brain cancer were available in the
beta version. Beta users have suggested improvements to survivorship plan templates.
Conclusion
The beta test of the app suggests that there is a demand for the application based on numerous letters and requests from
survivors and AYA clinics. Adding new cancer type templates for survivorship plans and other planned changes will make
the app more useful. The next version will be marketed more broadly and also will be used in survivorship research on the
use of persuasive tools for e-health.
Financial Disclosure (Deborah Vollmer Dahlke)
FDA Disclosure
Cleared:Yes
Keywords
survivorship
Adolescent and Young Adults
mobile
e-health
Abstract ID: 288
LIN28A and LIN28B Inhibit Biogenesis of the Tumor Suppressor Let-7 MicroRNA Family by Distinct Mechanisms
Author List
1. Additional Author: Elena Piskounova
2. Additional Author: Christos Polytarchou
3. Additional Author: James Thornton
4. Additional Author: Robert LaPierre
5. Additional Author: Charalabos Pothoulakis
6. Additional Author: Richard Gregory
7. Additional Author: Dimitrios Iliopoulos
8. Presenting Author: John Hagan
Oral Sessions
Oral Sessions
Status
Accepted
October 24, 2012 @ 01:25 PM
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
CPRIT_1figure.jpg
Summary
Introduction
Recent and provocative evidence suggests a novel form of post-transcriptional gene regulation involving 3â€™ RNA
uridylation mediated by Terminal Uridylyl Transferases (TUTases) as a critical driver of tumorigenesis. These data
indicate that dysregulated TUTase activity alone and in concert with the onco-fetal LIN28/let-7 pathway are hallmarks of
poor prognosis in multiple cancer types. The RNA binding proteins LIN28A and LIN28B are closely-related
proto-oncogenes that block selectively the expression of the tumor suppressor let-7 microRNA family. We previously
showed in mouse embryonic stem and embryonal carcinoma cells that the TUTase Zcchc11 is required for efficient
Lin28A-mediated let-7 repression. Here, we present our topical data on ZCCHC11 in LIN28A- and LIN28B-positive
human cancer cells [Cell (2011) 147:1066-79] and ongoing research.
Methods
In primary breast cancer and colon adenocarcinomas, immunohistochemistry evaluated LIN28A and LIN28B protein
expression, while in situ hybridization detected let-7 microRNAs. RNAi depleted the TUTase Zcchc11 in
several LIN28A- and LIN28B-positive cancer cell lines where we assayed mature let-7 levels by RT-qPCR in addition to
measuring cellular proliferation and migration. These studies were extended to subcutaneous xenograft mouse models
where we explored the feasibility of ZCCHC11 depletion as a novel cancer therapeutic by treating existing tumors by
intraperitoneal siRNA administration.
Results
LIN28A and LIN28B reactivation occurs frequently in breast and colon cancer. LIN28A and LIN28B expression is
strongly associated with HER2+ and triple negative (ER-, PR-, HER2-) breast cancers, respectively. LIN28+ tumors have
dramatic reductions in let-7 microRNA levels. Our knockdown studies in LIN28A-positive cancer lines demonstrate that
ZCCHC11 depletion elevates mature let-7 levels and reduces cellular proliferation and migration. Next, xenograft mouse
studies revealed tumor regression upon in vivo administration of ZCCHC11 siRNA. In contrast, ZCCHC11
loss did not affect let-7 levels and the oncogenic properties that we investigated in multiple LIN28B-positive cancer lines.
Conclusion
LIN28A and LIN28B block let-7 biogenesis by distinct mechanisms with differential reliance on the TUTase ZCCHC11.
Research is underway to reconcile reports that pre-let-7 is uridylated in all LIN28B-positive cancer lines investigated to
date, suggesting the involvement of an unidentified TUTase in let-7 regulation. We plan to investigate LIN28B and 3â€™
RNA uridylation more broadly in post-transcriptional regulation of gene expression and its relevance to tumorigenesis.
Also, we are developing a screen to identify chemical modifiers for the LIN28/let-7 pathway. Ultimately, small molecule
inhibitors of LIN28 or TUTase hold significant promise for treating roughly 15% of cancers characterized by LIN28
expression with its associated poor prognosis.
Financial Disclosure (John Hagan)
No
FDA Disclosure
Cleared:Yes
Keywords
microRNA
let-7
LIN28
TUTase
Abstract ID: 289
Preventing PAC/PICC Associated Bloodstream Infections
Author List
1. Additional Author: Lisa Brannan
2. Additional Author: Chelsea Crilly
3. Additional Author: Sylvia Danko
4. Additional Author: Gwen Irwin
5. Additional Author: Cyndie Lanne
6. Additional Author: Diane Martin
7. Presenting Author: Sandra Miller
8. Additional Author: Karla Smiley
9. Additional Author: Andrea Walker
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Every day in America cancer patients are admitted to hospitals to receive chemotherapy or for life saving infusions. Central
venous catheters play a central role in this cancer care. Unfortunately these patients are often immunocompromised and a
central line associated blood stream infection (CLABSI) can be life threatening. In 2008 at Seton Medical Center Austin
the inpatient oncology nursing team has aggressively taken on the challenge of preventing and reducing CLABSIâ€™s.
Methods
Initially the team had to face the prevailing notion that blood stream infections in this population were not preventable. The
purpose of this work then to decrease central line infection rates had to be rigorous and informed by the literature to
produce an evidence based approach. The idea was to engage a multidisciplinary team who would create a standardized
process easily used by all care providers. Overall the concept of â€œprotective measuresâ€• came together as a care bundle
of technical, education, communication and evaluation steps to eliminate variations in care and create standardized clinical
practice behaviors
Results
Early results showed drastic reduction in CLABSIâ€™s as infection rates decreased by 34% in the first year from 1.2/1000
patient day to 0.8/1000 patient day. The creation of a protective measures bundle coordinated care and communication
between nursing staff, support staff, physician offices and nursing leadership. Because of this success clinicians were lead
to new observations and information as all cases of infections that did occur were reviewed. Ongoing evaluation has led to
updates to the care bundle in April 2010, March 2012 and in May of 2012 to respond to new evidence or project learnings.
This performance improvement project reminds clinicians that infection prevention work is constant and unending.
Conclusion
The infection rates on this unit of primarily high risk patients have remained below national benchmarks for over three
years. The impact of this infection prevention work has spread across the network of Seton Hospitals as these best practices
have been added to central line care policy. It is recommended that all nursing leaders invest in nursing teamwork and
encouraging responsiveness to prevent infection. This investment save lives, reduces cost and increase access to oncology
care.
Financial Disclosure (Sandra Miller)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 290
Using The Survivorship Care Plan To Enhance Survivorsâ€™ Education, Communication, And Self Management
Of Their Long-term Needs
Author List
1. Presenting Author: Guadalupe Palos
2. Additional Author: Ludivine Russell
3. Additional Author: Katherine Gilmore
4. Additional Author: Fran Zandstra
5. Additional Author: Jacklyn Flores
6. Additional Author: Alma Rodriguez
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
CPRIT Table 1.jpg
Summary
Introduction
Patient-clinician communication and decision-making regarding self-management of cancer, a chronic disease, may be
improved through a survivorship care plan (SCP). Both the 2004 Presidentâ€™s Cancer Panel and the 2006 Institute of
Medicineâ€™s report, From Cancer Patient to Cancer Survivor, provided a basic SCP framework including a
treatment summary and recommendations to enhance communication between a cancer survivor, oncology provider, and
primary care physician about long-term survivorship cancer care. Here we describe how the SCP was used in
disease-specific survivorship clinics to enhance survivor-clinician communication during the clinic visit and to promote
survivorsâ€™ participation in the self-management of their follow-up care.
Methods
As part of a cancer survivorship management plan, survivorship care plans (SCPs) were developed to standardize care of
long-term cancer survivors. The SCP consisted of a treatment summary and recommendations for surveillance and
prevention, preventive health care, rehabilitation, and personal health behavior. The same framework was used in each
disease clinic and addressed 4 domains; surveillance for new/recurrent disease, monitoring for latent treatment effects,
counseling for risk reduction, and assessing psychosocial function. Referrals for institutional or community-based support
services related to exercise, nutrition, sexual function, and mental or social services were also made. Care plans differed in
some sections to better meet the specific recommendations for a particular disease. At the end of each visit, each survivor
received a survivorship care plan individualized to manage their specific cancer diagnosis and individual needs. A printed
copy of the care plan was given the survivor. Electronic copies of the care plans were also available through a web-based
system for the survivor and his/her authorized community providers.
Results
Results Table 1 provides a summary of the number of arrived appointments, completed survivorship care plans, and
percentages persurvivorship clinic from 09/02/2008 and 11/01/2011.
Conclusion
The survivorship care plan has the potential to promote survivor-clinician communication by helping the survivor
understand the benefits in participating in health promotion activities, making lifestyle changes to enhance their wellness,
and using referrals to available resources to accomplish changes recommended by their clinician. Patient-centered
communication will contribute to a better-informed survivor who may become a more active partner in decision-making
related to their care and self-management of their disease, which may improve their long-term survivorship outcomes.
Financial Disclosure (Guadalupe Palos)
No
FDA Disclosure
Cleared:Yes
Keywords
survivorship
cancer
None
None
Abstract ID: 291
Discovery Of MMP-2 Natural Product Inhibitors To Retard Oral Squamous Cell Carcinoma Invasion
Author List
1. Presenting Author: Trista Robichaud
2. Additional Author: Xiaoping Xu
3. Additional Author: Jiangnan Peng
4. Additional Author: Magarita Mikhailova
5. Additional Author: Susan Mooberry
6. Additional Author: Bjorn Steffensen
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Matrix metalloproteinases (MMPs) selectively cleave target collagens in vivo, and unbalanced protease expression and
activity are implicated in cancer progression. Oral squamous cell carcinomas (OSCCs) are seldomly detected early,
strongly express MMPs, and utilize MMP-2 to aggressively invade other tissues. Broad-spectrum MMP inhibitors have
adverse clinical side effects, making discovery of selective inhibitors highly desirable. Natural products have a long history
of efficacious and selective properties in cancer treatments. 
 
Objective: Develop a screening strategy for Texas plant extracts that are selective inhibitors of MMP-2. Identify
and validate lead compounds for inhibitor development.
Methods
Our screening strategies include: 1) Plant extract inhibition of fluorescence binding polarization by the FITC-labeled
dodecapeptide p713, which specifically binds the unique collagen binding domain (CBD) in MMP-2. 2) Inhibition of
MMP-2 catalyzed fluorescent gelatin cleavage, 3) Kinetic analysis of â€˜anti-targetâ€™ MMPs to ensure MMP-2
selectivity, 4) Plant extract fractionation 5) Extract derived active component identification and 6) Validate inhibitor
efficacy by retarding chemotaxis of OSCC cells in a Boyden chamber assay, and by preventing OSCC invasion into a
prototype 3-dimensional model of human oral mucosa.
Results
Among 320 extracts evaluated thus far, 35 extracts inhibited P713 binding of CBD in a concentration dependent manner,
reducing signal on the fluorescence polarization assay. Secondary screens identified 13 of these extracts that inhibited
MMP-2 cleavage of DQ gelatin at less than 250Âµg/ml IC50. JE7 (50Âµg/ml IC50) was
obtained in bulk and is now being processed using bioassay guided fractionation to identify active constituents in the
extract. In preparation for the cell culture assays, we have validated that OSCC chemotaxis and invasion and into a
fibroblast-containing 3D matrix are inhibited by a nonselective MMP inhibitor GM6001.Â
Conclusion
The experimental strategy thus far has identified extracts that inhibit MMP-2, and represent selective lead extracts. These
constituents have the potential to be developed into future therapies.Â
Financial Disclosure (Trista Robichaud)
No
FDA Disclosure
Cleared:Yes
Keywords
Natural Products
MMP2
Oral
Carcinoma
Abstract ID: 292
Lonestar: An Algorithm For Systematic Biomarker Discovery And Drug Response Prediction
Author List
1. Additional Author: Mehmet Ahsen
2. Presenting Author: Nitin Singh
3. Additional Author: Burook Misganaw
4. Additional Author: Todd Boren
6. Additional Author: Mathukumalli Vidyasagar
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Systematic analysis of genomic and molecular profiles of cancer patients to predict their response to a given drug is a
fundamental step in personalized medicine. One of the main objective of such an analysis is to identify patients' genomic
and/or molecular â€œsignatureâ€• â€“ preferably a small set of data-features such as genes â€“ that can be used to predict
their drug-response. In addition of being used as biomarker and prognosis-marker, thus identified signatures may provide
insight into drug/disease mechanisms. However, detecting such signature is a challenging problem that demands
development of new machine-learning techniques. To that end, we present a novel algorithm, Lonestar, and two
case-studies of its application. First, we identified a gene signature that can predict ovarian cancer patients' response to
platinum based therapy. Second, we identified a set of microRNAs that can be used to predict stage of endometrial
cancer.
Methods
We shall first describe our algorithm briefly and then move on to its applications. The Lonestar algorithm is a generic
machine-learning algorithm for binary classification that can be applied to a variety of problems including those discussed
here. In this algorithm, first a simple t-test is run to select features that are differentially expressed between two classes.
Subsequently, an L1-norm Support-Vector-Machine classifier is trained and those features that have very small weight in
the resulting classifier are eliminated. The second step is repeated recursively till there is no further reduction in number of
features.
In first application, Lonestar was employed to predict ovarian cancer patients' response to platinum based therapy. We
obtained microarray gene expression data for 585 patients and corresponding clinical information from TCGA. These
patients were divided into three groups: Responders (R, 57 patients), Medium-Responders (M, 475), Non-Responders (NR,
53) based on their disease-recurrence and mortality information. Then two classifiers, one for R-vs-M classification and
second for NR-vs-M classification were trained and validated using Lonestar algorithm. In second application, a classifier
was trained to predict stage of endometrial cancer (I or III) based on microRNA profile of 94 samples.
Results
In both cases, classifier performance was measured with 2-fold-cross-validation. These Lonestar based classifier made
prediction with high accuracy (>85% in ovarian and >80% in endometrial stage prediction) and resulted small set of
features (<30 genes and <15 microRNAs) that could be potential biomarkers.
Conclusion
These encouraging case-studies demonstrate that Lonestar might be widely applicable in genomic/molecular signature
identification.
Financial Disclosure (Nitin Singh)
No
FDA Disclosure
Cleared:Yes
Keywords
Biomarker discovery
Drug Response Prediction
Classification
Ovarian Cancer
Abstract ID: 293
P120-Catenin Binds The REST/CoREST Repressor Complex, And Modulates Gene Target Activity
Author List
1. Presenting Author: Moonsup Lee
2. Additional Author: Hong Ji
3. Additional Author: Pierre McCrea
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Wnt signaling pathways engage in multiple aspects of development, stemness and cancer. Although Î²-catenin is the key
signal transducer in canonical Wnt signaling, p120-catenin (isoform1) also becomes stabilized in response to Wnt signals.
P120 has an impact upon cadherin stability at junctions, small GTPase/ cytoskeletal functions, and nuclear transcription.
Loss of p120 is often found in epithelial cancers. With an aim to identify nuclear partners of p120, I resolved REST (RE1
silencing transcription factor) and CoREST. The REST/ CoREST complex represses neuronal fates in non-neural cells and
maintains embryonic and neural stem cell stemness. In cancer, REST acts as either a tumor suppressor or oncogene
depending on context. My ultimate goal is to understand p120â€™s relationship with REST/CoREST in stem cells.
Methods
HEK293T, HeLa, NIH3T3 or mouse stem cells were transfected or not with p120, REST and CoREST constructs, and
assayed via immunoprecipitation and immunoblotting, RT-PCR or immunofluorescence. In vitro transcription/ translation
was employed to assess direct protein:protein interactions. Xenopus embryo microinjections were employed for evaluating
phenotypes in an in vivo context.
Results
I found that p120-catenin associates with CoREST in vitro and in cells, and that their interaction is largely nuclear.
Supporting their functional interaction in both mammalian cells and Xenopus embryos, p120 depletion resulted in the
reduced expression of REST/CoREST gene targets (e.g. calbindin, mash1 and synaptotagmin4), while p120 expression had
the converse effect. Chromatin immunoprecipitations (ChIP) showed that exogenous p120 lowered REST binding to its
gene targets (calbindin, synaptotagmin4, and neuroD1), indicating that p120 may derepress gene targets via
REST/CoREST displacement from promoter DNA. Since REST/CoREST targets include neural genes, p120 may have an
impact on neural differentiation. Indeed, I preliminarily found that the depletion of CoREST produces eye defects in
Xenopus embryos, as is known to occur following the depletion of p120 subfamily proteins such as p120 and ARVCF.
Conclusion
My work is consistent with p120-cateninâ€™s direct interaction with REST/CoREST, and p120â€™s activation
(derepression) of REST/CoREST gene targets. Upon further study, these findings will assist in our understanding of
p120-cateninâ€™s nuclear roles, which ultimately may be coupled with those at cell-cell junctions. I will be going on to
evaluate the role of the p120/ REST/CoREST complex in mouse embryonic stem cells and neural stem cells. Ultimately, I
hope to obtain a better understanding of p120-cateninâ€™s roles in development and cancer, which may further extend to
the roles of additional p120-subfamily members, such as ARVCF- and delta-catenin.
Financial Disclosure (Moonsup Lee)
No
FDA Disclosure
Cleared:Yes
Keywords
p120-catenin
REST
CoREST
None
Abstract ID: 294
Roles Of The RFWD3 Ubiquitin Ligase On Nonalcoholic Fatty Liver Disease And Hepatocellular Carcinoma
Author List
1. Presenting Author: Nur Yucer
2. Additional Author: Anna Malovannaya
3. Additional Author: Sung Yun Jung
4. Additional Author: Yi Wang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Hepatocellular carcinoma (HCC) is a deadly malignancy that is increasing in incidence in developed countries. Although
infection by hepatitis B virus and hepatitis C virus, and alcoholic injury are the main causes of HCC, several large-scale
epidemiological studies have shown that Nonalcoholic Fatty Liver Disease (NAFLD) has a high risk to develop cirrhosis
and ultimately hepatocellular carcinoma. NAFLD is the most common liver pathology to describe a wide spectrum of liver
disease ranging from simple fatty liver (hepatic steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis with
increased risk of hepatocellular carcinoma (HCC). All of the stages of NAFLD are characterized by accumulation of fat in
the liver cell in a context of metabolic syndrome or insulin resistance. Current studies indicate that between 20%-30% in
the general population have a risk to progress to hepatic steatosis and this risk increases to 65%-75% in obese individuals.
In this study, we investigate the roles of the RFWD3 (Ring Finger and WD domain 3) ubiquitin ligase on NAFLD and
HCC by using a conditional knockout mouse strategy. In humans, the RFWD3 gene is located on chromosome 16q23.1.
This is a region that exhibits loss of heterozygosity in several cancers including breast cancer and HCC. Several studies
suggested that a minimal region of chromosome 16q23.1--24.1 harbors a tumor suppressor gene that contributes to the
pathogenesis of many HCCs. RFWD3 was identified as one of the putative ATM substrates and plays a role in
maintenance of the G1/S checkpoint. Our biochemical studies indicate that RFWD3 is required for stability of both p53
and MDM2 and it modulates MDM2-dependent ubiquitination of p53, rendering p53 resistant to 26S proteosome
degradation. We also showed that RFWD3 is involved the in replication checkpoint through binding to replication protein
A (RPA) and plays a role in DNA replication and repair.
Methods
We generated the liver specific Rfwd3 knockout mice and performed biochemical, cellular and pathological assays. We
carried out the protein profiling by using mass spectrometry and also DNA affinity pull-down / mass spectrometry for
transcription factor (TF), followed by WB analyses of selected TFs . We used histological tools such as HandE and
Oil-Red staining for pathological investigation.
Results
Loss of Rfwd3 led to the development of NAFLD in early ages by inducing lipogenic pathways.
Conclusion
Rfwd3 is an important regulatory protein for lipid metabolism in mice liver and lots of it causes the progession of HCC by
suggesting that Rfwd3 is a potential tumor suppressor.
Financial Disclosure (Nur Yucer)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 295
Studying Astrocyte Lineage Progression To Gain A Better Understanding Of GBM Constituency And
Heterogeneity
Author List
1. Presenting Author: Lesley Chaboub
2. Additional Author: Benjamin Deneen
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Glioblastoma multiform is the most prevalent type of brain tumor in the adult and has a very poor prognosis. These tumors
are particularly heterogeneous, both morphologically and genetically, and are comprised of progenitors (neural and glial)
and astrocytes. While much attention has been dedicated to the cellular contribution of progenitors, our understanding of
glial precursors, particularly astrocytes, remains poor. We propose a novel screen to better comprehend astrocyte
development from their specification to their final differentiation in order to identify new markers to enhance GBM
characterization.
Methods
We used the previously described reporter mouse line Glast::DsRed as Glast is the most accurate astrocyte precursor
marker; remains expressed in certain regions of the central nervous system (CNS) during adulthood; and the reporter
properly recapitulates Glast expression during development. We focused on the spinal cord because several aspects in the
timing of astrocyte development have been defined, while these properties are not as well established in other CNS regions.
In the mouse spinal cord glial/astrocyte precursors emerge at E12.5 and become fully mature by E18.5, as defined by
GFAP expression. We also extended our analysis to include two post-natal time points since GFAP expression is not
always correlated with functional differentiation.
Results
Briefly, spinal cords from mouse embryos (E12.5, E14.5 E16.5 and E18.5) or pups (P4 and P7) were harvested and
dissociated. Using fluorescence-activated cell sorting, we collected cells expressing the reporter DsRed, but not the stem
cell marker CD15 (DsRed+/CD15-). RNA was then harvested and subjected to Affymetrix Exon microarray profiling at
the Baylor College of Medicine Gene Expression Profiling core. As a control, we also harvested DsRed-/CD15- cells to
remove all housekeeping genes and non-astrocytes genes.
Conclusion
Upon obtaining the results, our analysis will focus on 1) obtaining a unique signature for each time point and 2) finding
genes which expression changes over time, potentially marking a specific stage in development (i.e. migration vs.
differentiation). After validation of such genes using In Situ Hybridization during spinal cord development, we will further
study the expression of these genes in the adult brain and in GBM samples. 
Such a screen will not only further our knowledge of astrocyte development, but may be extrapolated to the cancer research
field, in particular to better understand the constituency of GBM.
Financial Disclosure (Lesley Chaboub)
No
FDA Disclosure
Cleared:Yes
Keywords
GBM
astrocyte
development
Glast
Abstract ID: 296
NQO1 In Antioxidant Defense: Implication For Prostate Tumorigenesis And Castration Resistance
Author List
1. Presenting Author: Dinesh Thapa
2. Additional Author: Addanki Pratap Kumar
3. Additional Author: Rita Ghosh
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
NAD(P)H-Quinone Oxidoreductase 1 (NQO1) is a key antioxidant enzyme that protects against quinone derived reactive
intermediates and maintains a cellular pool of antioxidants. NQO1 also regulates the stability of p53 tumor suppressor
protein and cell fate decisions in response to endogenous and exogenous stress, such as oxidants, inflammation and
carcinogens. Recent studies from our laboratory and others have found that expression levels of NQO1 and several GST
family genes are significantly suppressed in prostate tumors in preclinical mouse models.
Methods
To investigate the role of NQO1 in prostate carcinogenesis, we employed various cellular, molecular and genetic
approaches including signal transduction, microscopy, proteomics, oncogenomics, RNAi, utilizing normal as well as
prostate cancer cell lines in vitro.
Results
We generated NQO1-knockdown stable clones in hormone responsive (LNCaP) and hormone-independent (C42B, PC3
and DU145) prostate cancer cells. Chronic hormone deprivation induced growth arrest in cells containing non-targeted
control shRNA (LNCaP-scr) while hormone exposure supported cell survival. On the other hand NQO1 knockdown cells
(LNCaP-shNQ) managed to escape from hormone deprivation-induced death/growth arrest. Whole genome microarray
analysis of these two clones revealed deregulation of 1603 signature genes. NQO1 silencing induced an important subset of
genes involved in inflammation, growth, angiogenesis as well as antioxidant defense system, many of which have been
implicated in prostate cancer progression. For example, pro-inflammatory genes such as IL-32, IL-8, MCP-1/CCL2, IL1R2
were highly upregulated (>6 fold; p<0.01). We further validated these changes by real-time qPCR. Using human cytokine
array, we clearly observed increased IL-8 secretion in conditioned media collected from LNCaP-shNQ cells as compared
to LNCaP-scr cells. On the other hand, stable knockdown of NQO1 in PC3 cells inhibited cell proliferation, colony
formation and migration. No significant changes in cell proliferation and colony formation were observed in DU145 cells.
Furthermore, human cytokine array revealed that NQO1 silencing differentially modulated several important cytokines
including G-CSF, GM-CSF, IL-1, IL-8, MCP-1.
Conclusion
Collectively blocking NQO1 may regulate cellular redox status, which in turn, possibly control cellular response to
hormone, cell proliferation, antioxidant and pro-inflammatory pathways. However, the mechanism by which the
differential expression of these genes and cell fate are regulated through NQO1 still remains to be elucidated. The current
study indicates that antioxidant NQO1 regulates various cellular processes. Since these diverse actions influence cellular
response to hormones, oxidants and carcinogens, strategies modulating cellular antioxidants to regulate NQO1 and other
important players in NQO1-signaling may provide multifaceted opportunities for prostate cancer prevention.
Financial Disclosure (Dinesh Thapa)
No
FDA Disclosure
Cleared:Yes
Keywords
NQO1
Prostate cancer
oxidative stress
IL-8
Abstract ID: 297
Development Of Biodegradable Nanoparticles For DNA And RNAi Delivery
Author List
1. Presenting Author: Fude Feng
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Current polymeric delivery of siRNA and DNA has some limitations such as broad distributions and large sizes of
nanoparticles that limit the penetration of particles in tumor. Well-defined polymeric nanoparticles are urgently needed to
improve the pharmacokinetics, biodistribution and therapeutic efficacy of the polymeric particles.
Methods
Bio-degrable cationic polymers form nanoparticles with siRNA in a controllable size and shape. pH-responsive groups are
introduced into the side chain of polymers to allow for effective endosome escape for siRNA delivery. The particles with
siRNA packed inside can be be taken up by tumor cells. The pharmacokinetics, biodistribution, circulation and therapeutic
efficacy of the particles will be measured. DNA delivery can also be studied using these polymers to enhance gene
transfection.
Results
A linear bio-degradable PEG-modified polymer is prepared with narrow molecular weight distribution. Also, a novel
star-shaped core-shell polymer is prepared.
Conclusion
Structurally-different bio-degradable polymers are prepared via ring-opening polymerizations, which will be further
applied for targeted DNA and RNAi delivery.
Financial Disclosure (Fude Feng)
No
FDA Disclosure
Cleared:Yes
Keywords
polymeric nanoparticle
siRNA delivery
DNA delivery
None
Abstract ID: 298
Head And Neck Cancer In Texas: A Population-based Study
Author List
1. Presenting Author: Carol Lewis
4. Additional Author: Janice Cormier
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Detailed information about how head and neck cancer is treated across a variety of practice settings and patient populations
has not been widely reported.
Methods
We used Texas Cancer Registry-Medicare linked data (2001-2007) to identify 4,783 cases of upper aerodigestive tract
cancer in patients ages 66 and older in Texas. We examined patient demographic characteristics and primary course of
treatment. Kaplan-Meier survival analysis was used to examine overall survival (OS) and disease-specific survival (DSS)
for the overall cohort and by subsite of disease and type of treatment.
Results
Two-thirds of patients were male, with a median age of 74 years (range 66 to 104 years). The majority of patients (86%)
were white. At the time of diagnosis, 44% had localized tumors, 33% had regional spread, and 12% had distant metastases.
The most prevalent subsite of disease was oral cavity (42%), followed by larynx/hypopharynx (38%), oropharynx (9%),
salivary gland (8%), and nasopharynx (2%). Patients were treated with definitive radiation (31%), surgery (31%), and
surgery with adjuvant radiation (28%). No treatment was identified for 11% of patients. OS and DSS for treated patients
were 62% and 78%, respectively, at 2 years and 41% and 75%, respectively, at 5 years. Salivary gland and laryngeal
cancer patients had the best 5-year DSS (86% and 78%, respectively) and nasopharyngeal cancer patients the worst 5-year
DSS (51%). DSS was similar across all treatment types.
Conclusion
Nearly 90% of upper aerodigestive tract cancer patients presented with curable disease, with OS and DSS comparable to
historical data. There was no survival advantage for any one treatment type. DSS was best for salivary gland and laryngeal
cancer patients and worst for nasopharyngeal cancer patients.
Financial Disclosure (Carol Lewis)
No
FDA Disclosure
Cleared:Yes
Keywords
upper aerodigestive tract
head and neck cancer
survival
treatment
Abstract ID: 299
Cell-Assay-on-a-Chip To Study Tumor Initiating Cell Heterogeneity And Treatment Resistance
Author List
1. Additional Author: Weijia Zhang
2. Presenting Author: Lidong Qin
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
Figure 1.jpg
Summary
Introduction
Tumor Initiating Cells (TIC) have a few intrinsic properties that lead to challenges in molecular targeting and inhibition,
particularly for personalized treatment. TICs are 1) heterogeneous, 2) dynamically changing states, 3) often rare and 4) lack
robust biomarkers/biomarker combinations, hence challenging conventional bulk in vitro experimental tools and
complicating the prediction and explanation of animal results. It is clear that high throughput, in situ, and cell-by-cell
measurements on TICs are urgently need to fully decipher the TIC molecular signature and signaling pathways. We believe
such measurements can lead to 1) revolutionary implementation of TIC models; 2) identification of new therapeutic
targets; and 3) reduction of breast cancer recurrence and metastasis. Therefore, we utilize our Single Cell Barcode Chip
(SCBC) platform to characterize protein expression from individual breast TIC. The approach is based on a high
throughput microfluidics technology to measure in situ protein production from enriched TICs at single cell sensitivity.
Our investigation may lead to discovery of new signaling mechanisms of TIC renewal and survival, and identify new drug
targets to eliminate TICs.
Methods
We started pursuing such measurements a few years ago and demonstrated high throughput single-cell protein profiling on
both cell lines and clinical samples. The technology, called single-cell barcode chip (SCBC), is facilitated by
state-of-the-art Polydimethylsiloxane (PDMS) microfluidics protocols. The SCBC consists of down to nanoliter chambers
that concentrate proteins from individual cells to a level even higher than cell culture media in conventional dish
technology and contains extremely miniaturized antibody arrays to capture proteins produced by cells in these chambers.
Herein, we utilize our SCBC platform to characterize protein expression from individual breast TICs.
Results
We have first studied TIC heterogeneity and investigate the unique cellular characters at play. By applying enriched TIC
candidate cells to SCBC and in situ culturing, we have measured proteins produced from individual cells over a panel of
functions including self-renewal capability, mammosphere forming capability, and also surface biomarkers.
Conclusion
We have collected TICs, prepared SCBC and SCBC-LST chips, and loaded TIC cells to chips for TIC protein expression
data collection. We have also established a protein panel to study TIC and collect barcode data from enriched TIC cells. By
studying TIC proliferation/differentiation protein expression with its cell surface markers and intracellular proteins, we
have found the existence of TIC subtypes and their molecular expression characters. The research may be helpful to guide
the selection of TIC inhibitors for future research.
Financial Disclosure (Lidong Qin)
No
FDA Disclosure
Cleared:Yes
Keywords
Tumor Initiating Cells
Cell Assay on a Chip
Microfluidics
None
Abstract ID: 300
Multiple Catenin Proteins Contribute To Development And Cancer: Emerging Roles Of The Plakophilin-3 Catenin.
Author List
1. Presenting Author: William Munoz
2. Additional Author: Malgorzata Kloc
3. Additional Author: Kyucheol Cho
4. Additional Author: Moonsup Lee
5. Additional Author: Ilse Hofmann
6. Additional Author: Amy Sater
7. Additional Author: Kris Vleminckx
8. Additional Author: Pierre McCrea
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Desmosomes contribute to the exchange of cell-cell signals, and the physical integrity of junctions and tissues. They are
comprised of transmembrane cadherin super-family members, and intracellular components that include desmoplakin,
intermediate filaments, as well as catenin proteins (plakophilins 1-3 & plakoglobin). The most prominent non-desmosomal
catenin family member is beta-catenin, which is a key player in both development and cancer progression. This work
instead focuses upon Plakophilin-3 (Pkp3), a catenin whose misexpression has been associated with metastatic potential.
Based upon what we know about catenins generally, we hypothesized that Pkp3 has key functions in embryogenesis and
adult tissues, and that it acts in more than one intracellular compartment.
Methods
In this study we used Xenopus laevis as an in vivo model system. It allows us to microinject to deplete or overexpress gene
products, followed by embryo assessment via whole-mount in situ hybridization, immunofluorescence, real-time sqPCR,
immuno-blotting, or scanning and transmitted electron microscopy (etc.). Additionally, I will be including preliminary
Pkp3 protein-interaction data from human HeLa cells. In these cells, Pkp3 was targeted in an ectopic fashion to the
mitochondrial outer membrane via a fusion tag, while potential binding partners were co-expressed and scored for ectopic
corelocalization, indicating an association.
Results
We will present our characterization of Pkp3 in early vertebrate embryos of Xenopus laevis. For example, Pkp3 is resident
at both desmosomal junctions and in the cytosol, with our recent data further suggesting roles in gene regulation in the
nucleus. Additionally, we will include Pkp3 temporal and spatial profiling, and knockdown phenotypes indicating its
requirement in amphibian development. Depletion effects include touch hyposensitivity, and reductions in certain neural
tracts, cilia and ectodermal integrity. While Pkp3 knock-out mice likewise exhibit epithelial fragility, the neuronal and cilia
phenotypes have not been previously reported. Finally, we will show Pkp3â€™s first association with nuclear binding
partners.
Conclusion
We find that Pkp3 is essential for late embryonic development, with roles in ectoderm and neural tissue development
(Munoz et al., 2012). Importantly, we have just identified the first nuclear binding partners of Pkp3, including known
transcriptional regulators involved in neuronal functions. Our goal is to deepen the cellular and developmental
understanding of Pkp3, with future work focusing upon its poorly understood roles in the nucleus. This will assist in
learning if Pkp3â€™s functions in gene regulation are linked to that at cell-cell junctions, and how its misexpression in
carcinomas is associated with metastatic potential.
Financial Disclosure (William Munoz)
No
FDA Disclosure
Cleared:Yes
Keywords
catenin
development
transcription
plakophilin
Abstract ID: 301
Quality Of Life And Psychosocial Distress Among Cancer Survivors Enrolled In The Fort Worth Program For
Community Survivorship
Author List
1. Presenting Author: Heidi Hamann
2. Additional Author: Paula Anderson
3. Additional Author: Elsa Inman
4. Additional Author: Bonnie Rose
5. Additional Author: Suzy Lockwood
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
With nearly 12 million cancer survivors in the US, there is a growing need to provide psychosocial and behavioral services
that address emotional adjustment, health behavior goals, and other practical and support needs. With support from a
CPRIT Prevention grant (PP110097), the Fort Worth Program for Community Survivorship (ProComS) was developed to
address these psychosocial and behavioral needs of our cityâ€™s cancer survivors. With collaboration from community
partners, our evidence-based, multidisciplinary survivorship services have been unified under a common framework,
creating an innovative, community-led initiative. The goal of the current analysis was to measure changes in quality of life
(QOL) and psychosocial distress among ProComS participants who completed assessments at time of enrollment and 3
months later.
Methods
We focused on baseline (initial survivorship consult) and 3-month follow-up data from the first 45 program participants
who completed assessments at both timepoints. Health-related QOL was measured by the Functional Assessment of Cancer
Treatment-General version (FACTâ€•G) and psychosocial distress was assessed by the Brief Symptom Inventory
(BSIâ€•18).
Results
We observed a statistically significant improvement in overall QOL scores for ProComS enrollees (p < .01). Mean QOL
scores rose from 77.9 at clinic entry to 83.6 just three months after starting the survivorship program. Statistically
significant improvements were also seen within the specific QOL domains of emotional, physical, and functional
well-being. Reports of overall psychosocial distress, including subscales of depressive symptoms, anxiety, and somatic
concerns, also decreased during the 3-month clinic period (Baseline M=12.6; 3-month follow-up M=11.0; not statistically
significant, but a clear trend in results).
Conclusion
Overall, these preliminary data are good indicators that after 3 months of enrollment in ProComS, cancer survivors
reported better QOL and were less distressed. We cannot attribute, with certainty, these improvements to survivorship
activities and referrals. However, these data lend support to the assertion that our services offered meaningful and
measureable benefits to cancer survivors. We look forward to expanding these assessments to more clinic participants and
learning about the longer-term impact of our survivorship services.
Financial Disclosure (Heidi Hamann)
No
FDA Disclosure
Cleared:Yes
Keywords
Survivorship
Quality of Life
Psychosocial Distress
Cancer survivors
Abstract ID: 302
An RNAi-based Functional Classification Of Lung And Breast Cancers Reveals Recurring Subgroups Strongly
Correlated With EMT Status
Author List
1. Presenting Author: Ryan Carstens
2. Additional Author: Kenneth Huffman
3. Additional Author: Heidi Erickson
5. Additional Author: Luc Girard
7. Additional Author: Carmen Behrens
8. Additional Author: Ignacio Wistuba
9. Additional Author: Hui Tian
10. Additional Author: Sandra Hofmann
11. Additional Author: Adi Gazdar
12. Additional Author: Steven Kliewer
14. Additional Author: David Mangelsdorf
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Introduction: Personalized therapeutic approaches which stratify patients into subgroups based on
mutation, amplification, or expression profiles have proven effective. Previously, we showed that mRNA expression
profiling of nuclear receptors (NRs) segregated NSCLC patients into prognostic groups. Using a gene-library knockdown
strategy, we aim to demonstrate the diagnostic and therapeutic value of NRs and their co-regulators (Co-Regs).
Methods
Aims and Methods: We used a large panel of lung and breast cell lines of various types to develop a
patient stratification scheme based on functional/survival response to pooled siRNA â€œminiâ€• library screens. The first
siRNA mini-library consists of 48 NR and 72 CoReg targets. Screens were performed in triplicate across a panel of 54 lung
cancers (NSCLC and SCLC), 20 breast cancers, 6 immortalized human bronchial epithelial cell lines (HBECs), and a series
of oncogenically progressed HBECs. Each triplicate assay was repeated three times using optimized transfection conditions
and followed by statistical analysis (r>0.83 for replicate screens). A second siRNA library targeting 53 chromatin
remodelers, 26 jumonji enzymes, and 23 palmitoyl transferases was also screened against these same lines using the same
protocol.
Results
Results: 1) Response (inhibition or stimulation of growth) to any given siRNA
knockdown was heterogeneous across the panel, reflecting the high degree of genetic/functional variability between cancer
lines. 2) 85% of the siRNA knockdowns reduced viability in at least one tumor line. Several
knockdowns demonstrated selective killing of a significant portion of the cancer lines but not the â€œnormalâ€• HBECs.
Some knockdowns differentially affected subsets of cell lines while others uniformly affected nearly the entire panel.
3) Screening a series of oncogenically progressed HBECs (with p53, KRAS, LKB1) revealed new
vulnerabilities detected by a change in response to NR/CoReg knockdown, highlighting the underlying biological changes
accompanying oncogenesis. 4) Unexpectedly, we found that classification of the tumor cells by the
NR/CoReg mini-library was similar to the classification derived from the second library. The two libraries independently
produced a similar subgrouping of the tumor panel. Combined analysis of the two libraries found similar groups.
5) Although there was no obvious correlation between the subgroups and oncogenotypes or mRNA
expression of individual NRs or CoRegs, one subgroup (n=26) consisted almost exclusively of lines that had undergone
EMT, suggesting possible subtypes of mesenchymal cells.
Conclusion
Conclusion: We conclude that siRNA-minilibrary screens targeting NRs, CoRegs, and chromatin
remodeling genes provide a new functional classification of lung and breast cancer with strong translational potential.
Financial Disclosure (Ryan Carstens)
No
FDA Disclosure
Cleared:Yes
Keywords
Lung Cancer Subclassification Scheme
RNAi Screening
NHRs/CoRegs
EMT
Abstract ID: 303
Development, Validation, And Clinical Application Of A Prognostic GEP Signature (decisiondx-thymoma) For
Determination Of Metastatic Risk In Thymomas
Author List
1. Presenting Author: Robert Cook
2. Additional Author: Yesim Gokem-Polar
3. Additional Author: Chirayu Goswami
4. Additional Author: Derek Maetzold
5. Additional Author: Kristen Oelschlager
6. Additional Author: John Stone
7. Additional Author: Jeff Wilkinson
8. Additional Author: Ioan Vladislav
9. Additional Author: Kristen Shirar
10. Additional Author: Kenneth Kesler
11. Additional Author: Patrick Loehrer Sr.
12. Additional Author: Sunil Badve
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Thymomas are rare tumors that are predominantly characterized by the stage of disease, yet thymomas of every stage can
give rise to metastases. We sought to develop a molecular-based prognostic tool for the determination of metastatic risk in
thymomas. In a CAP accredited / CLIA certified laboratory, we adapted the results of a whole genome expression analysis
of thymic tumors to an RT-PCR platform using a set of genes associated with presence or absence of metastases. A training
set of 36 thymomas of low or high risk was identified and clinically validated using a multi-institutional, 75-sample
validation set of thymomas.
Methods
Cases of thymomas with archival blocks and long-term follow-up data were reviewed. RNA was extracted under CLIA
procedures from 5x10-micron thick sections, converted to cDNA, and analyzed using custom TLDA cards on an ABI7900
instrument. All laboratory personnel per blinded to clinical status. Thymoma samples to be included in the training set were
selected based upon the clinical parameters of time to metastasis or longest follow-up time without a metastatic event and
without regard for molecular profiling. Clinical validation of the test set was performed using an independent set of 75
thymoma tumors. The non-linear SAS radial basis machine predictive model was used to assess the ability of the gene
signature to predict metastatic behavior.
Results
The 19-gene signature predicts low risk (class 1) or high risk (class 2) of metastasis. We compared gene expression profile
class to histologic stage using Kaplan-Meier analysis of the 75-sample validation cohort. 5-yr MFS was 93% and 35% for
class 1 and class 2, respectively (P=0.0018). Comparably, 5-yr survival was 53% and 41% for tumors classified as
non-invasive (stage I and II) and invasive (stage III/IV) by Masaoka stage histology, respectively (P=0.032). Further, Cox
regression multivariate analyses identified the 19-gene signature as the only independent predictor of metastasis, with a
hazard ratio of 7.76 (P=0.048).
Conclusion
Through a collaborative effort between academic and industrial organizations, we have rapidly and efficiently developed
and validated a 19-gene signature for predicting the metastatic potential of thymomas. The cooperative development
process can serve as a template for the advancement of genetic assays that can provide valuable information to patients
with rare malignancies.
Financial Disclosure (Robert Cook)
No
FDA Disclosure
Cleared:Yes
Keywords
thymoma
gene expression profile
rare cancer
metastasis
Abstract ID: 304
Recruiting Clinics In Harris County, Tx, To Conduct Intervention Study Of Human Papillomavirus Vaccination
Among Hispanic Adolescents: Successes And Challenges
Author List
1. Additional Author: Maria Fernandez
2. Presenting Author: Barbara Kimmel
3. Additional Author: Lara Savas
4. Additional Author: Natalie Fernandez-Espada
5. Additional Author: Nancy De La Fuente
6. Additional Author: Chakema Carmack
7. Additional Author: Angelica Roncancio
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Hispanic women in the United States have the highest incidence rate of cervical cancer compared to women in other racial
groups. Although HPV vaccine has been available for several years, uptake and completion rates among Hispanic girls
continue to be low (56.2% and 29.5%, respectively). This randomized trial will evaluate the effectiveness of two
clinic-based interventions aimed at increasing HPV vaccination among Hispanic adolescents (an iPad-based interactive
multimedia intervention and a print media photonovela). We describe our experience recruiting and enrolling 32 clinics
serving the target population.
Methods
We focused recruitment on the Harris County Hospital District (HCHD), Federally Qualified Health Clinics (FQHC), and
private clinics serving low-income and Hispanic patients. Clinics were eligible for inclusion in the study if they keep the
vaccine in stock and served adolescent population. To identify potentially eligible clinics among 46 community health
centers, a short self-administered clinic survey was completed by clinic staff. Structured clinic observations were also
conducted by study coordinators to describe institutional and organizational factors (e.g., patient population
sociodemographic characteristics, numbers and types of providers and clinicsâ€™ administrative staff). Clinic observations
described patient flow and other clinic environment variables. Once we identified eligible clinics, the recruitment process
involved several different forms of communication, including phone calls, emails and in-person meetings. This time
consuming process included multiple attempts to communicate with clinic managers and obtain clinic information.
Results
Initially, 46 clinics were screened. Two of them did not stock the vaccine and 3 served adults only. This resulted in 41
eligible clinics, of which 32 agreed to participate. The subsequent IRB approval process took 6 to 8 months, depending on
the site. Clinic type distribution was: 16 private, 10 HCHD and 6 FQHC/Nonprofit. Size varied from 280-6000 patients
served per month. Challenges included 9 clinics that were unresponsive or refused to participate. Among refusals, some
clinics already had other programs or studies in place and could not participate in another study.
Conclusion
Despite challenges, we achieved the desired number of clinics. CHC and private clinics are ideal settings to study culturally
appropriate and tailored interventions to increase HPV vaccination among Hispanics. To effectively identify and recruit the
large numbers of clinics for multisite studies, efforts must be made to understand their institutional and organizational
challenges and patient-related issues.
Financial Disclosure (Barbara Kimmel)
No
FDA Disclosure
Cleared:Yes
Keywords
Abstract ID: 305
Moving T Cell Therapies To Late Phase Clinical Trials
Author List
1. Presenting Author: Serena Perna
2. Additional Author: Minhtran Ngo
3. Additional Author: Jun Ando
7. Additional Author: Barbara Savoldo
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Immunotherapies using cytotoxic T lymphocytes (CTLs) are showing increasing success for the treatment of malignancy.
Of these, EBV-positive Hodgkin and non-Hodgkin lymphomas are susceptible to T-cells directed against the
Epstein-Barr-Virus (EBV) latent cycle antigens, LMP1 and LMP2, and these CTLs have induced complete responses in
more than 60% of patients with multiply relapsed or refractory disease. Unfortunately, current CTL generation protocols
are difficult to scale and are insufficiently robust for wider application as â€œstandard of careâ€•. For example, the use of
live virus (EBV) and adenoviral (Ad) vectors and the difficulty of generating EBV-transformed B-cell lines (EBV-LCL)
from B-lymphoma patients are major impediments.
Methods
To overcome the above and other limitations, we replaced the source of adenoviral antigens with overlapping peptide
libraries (pepmixes) that span the entire antigen sequences of LMP1, LMP2, EBNA1 and BARF1 (all expressed in EBV+
lymphoma). As APCs to expand the antigen-specific T-cells, we replaced autologous EBV-LCLs with peptide-pulsed,
irradiated autologous activated T-cells (AATCs), together with irradiated artificial costimulatory cells (HLA-negative
K562 cells genetically modified to express CD80, CD86, CD83 and 41BB-ligand [K562-CS]). Antigen-specific T cells are
therefore generated by stimulating patient peripheral blood T cells with pepmix-pulsed, mature, autologous dendritic cells
and expanded using pepmix-pulsed AATCs and K562-CS cells. Moreover, we will improve patient responses by
enhancing in vivo CTL expansion and persistence. We will exploit the properties of IL-7 to overcome this deficiency. IL7
is a homeostatic ï•§c cytokine that increases physiologically in response to lymphopenia. We are engineering the CTLs to
express the interleukin 7 receptor alpha (IL-7Rï•¡). We have previously shown that such expression restores the
responsiveness of activated T-cells to IL-7 without altering their antigen specificity. We expect that endogenous levels of
IL-7 will support the proliferation of these transgenic EBV-CTLs but, if physiological IL-7 concentrations are insufficient,
patients will receive the recombinant protein.
Results
Our studies are in the process of being implemented but we hypothesize that, in patients with EBV+
Hodgkin/Non-Hodgkin lymphomas, we will confirm the safety, feasibility and clinical equivalency of our newer, faster and
safer approach and that tumor responsiveness will be further enhanced when the CTLs express a transgenic IL7Rï•¡.
Conclusion
Our approach will then be transferred to industry-sponsored, pivotal late phase clinical trials in patients with EBV+
Hodgkin/Non-Hodgkin lymphomas.
Financial Disclosure (Serena Perna)
No
FDA Disclosure
Cleared:Yes
Keywords
T cell immunotherapy
EBV-positive
Hodgkin/Non Hodgkin Lymphoma
None
Abstract ID: 306
Novel Approaches To Antagonize Androgen Receptor Activity In Prostate Cancer
Author List
1. Presenting Author: Aihua Yen
2. Additional Author: Donald Rao
3. Additional Author: John Nemunaitis
4. Additional Author: Neil Senzer
5. Additional Author: Zhaohui Wang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Metastatic prostate cancer (PCa) is responsive to androgen deprivation therapy (ADT), but its long term use is limited by
serious side effects and inevitably, the development of castration-resistant prostate cancer (CRPC). Despite therapeutic
reduction of serum testosterone to castration levels, the androgen receptor (AR) remains a viable target in CRPC, as
demonstrated by recent phase III clinical trials in post-docetaxel CRPC patients showing significant survival benefits with
abiraterone and enzalutamide. There are multiple mechanisms for how CRPC occurs, including the expression in CRPC of
constitutively active AR splice variants lacking the ligand binding domain (LBD) but able to activate AR target genes.
Thus, these would exhibit resistance to therapeutics which inhibit AR through its C-terminus LBD, such as abiraterone and
enzalutamide. Therefore, new methods of inhibiting AR regardless of ligand-binding are urgently needed. Currently, we
are testing three novel approaches to antagonize receptor expression and activity: RNAi-based knockdown using
bifunctional shRNA targeting AR (bishAR), proteasome inhibition by MLN2238, and AR inhibition by gossypol.
Methods
BishARs to the AR N-terminus, which can both cleave mRNA and inhibit translation, were designed by Gradalis. HeLa
and LNCaP cells were transiently transfected with bishAR. Protein expression was analyzed with western blots or
immunohistochemistry, and mRNA expression was measured with RT-qPCR. 5â€™ RLM-RACE was used to detect
bishAR-mediated mRNA cleavage. LNCaP cells treated with gossypol, MLN2238, and bortezomib were evaluated by
western blots and RT-qPCR.
Results
Four candidate bishARs were tested, and the one with the most efficient AR knockdown in transfected HeLa cells was
selected for further testing. Evidence of mRNA cleavage and translational inhibition was confirmed in bishAR treated
cells. Generation of specific mRNA cleavage products was detected by 5â€™ RLM-RACE in parallel to reduction of AR
expression and activity. Immunofluorescence also confirmed bishAR mediated AR knockdown. Gossypol and proteasome
inhibitors not only reduced AR protein expression and activity, but surprisingly reduced AR mRNA expression as well. To
gain mechanistic insight, we have generated cell lines inducibly expressing AR to evaluate for effects on AR activity.
Conclusion
These three methods inhibit AR expression and activity in cell culture models of androgen-dependent PCa. Combining
these approaches may synergistically block AR expression or activity, and further in vivo experiments are warranted. The
bishRNA technology, MLN2238, and gossypol are already in clinical development for other non-prostate cancers, and after
completion of our preclinical testing, we will advance these approaches to the clinical phase of testing.
Financial Disclosure (Aihua Yen)
No
FDA Disclosure
Cleared:Yes
Keywords
prostate cancer
shRNA
proteasome inhibitor
gossypol
Abstract ID: 307
Developing An Immune Competent Animal Model For GBM-Targeted T-cell Therapy
Author List
1. Presenting Author: Tania Rodriguez
2. Additional Author: Kevin Chow
3. Additional Author: Melinda Mata
4. Additional Author: Zhongzhen Yi
5. Additional Author: Leslie Huye
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
N/A
Introduction
Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in humans and is virtually incurable
with current standard therapies. Thus, new targeted treatments are needed to improve outcomes, and adoptive
immunotherapy has the potential to fulfill this need. Erythropoietin-producing hepatocellular A2 (EphA2) receptor is
overexpressed in GBM, and we have shown in immune deficient xenograft models that human T cells expressing
EphA2-specific chimeric antigen receptors (CARs) have potent antitumor activity. We are now interested in combining
EphA2-CAR T cells with other targeted therapies. In this regard an immune competent animal model is essential to
evaluate the interactions between infused T cells and the host. The goal of this project is now to develop such a model.
Methods
We 1st demonstrated that our EphA2-specific CAR recognizes murine EphA2 as judged by the ability of human
EphA2-CAR T cells to secrete IFN-Î³ in response to recombinant murine EphA2 protein. Since our original
EphA2-specific CAR contained human signaling domains, we replaced the domains with murine sequences to prevent
CAR-specific immune responses in the murine host.
Results
The generated murine EphA2-specific CAR is functional, and we are currently generating a retroviral producer cell line to
produce retroviral particles for the transduction of murine T cells. In addition, we have identified a transplantable murine
glioma cell line (GL261) that is EphA2 positive and is killed by CAR T cells in cytotoxicity assays in an EphA2-specific
manner.
Conclusion
Our results indicate that it is feasible to develop an immune competent murine GBM-targeted T-cell immunotherapy
model. Such a model will not only facilitate the translation of these therapies into the clinic, but will also allow us to
realistically study how to best combine T-cell therapy with other GBM-targeted therapies.
Financial Disclosure (Tania Rodriguez)
No
FDA Disclosure
Cleared:Yes
Keywords
Glioblastoma
T cells
Chimeric Antigen Receptors
Immunotherapy
Abstract ID: 308
Matrix Analysis Of Genome-wide RNAi Screens And Copy Number Variation In Melanoma Samples For Isolation
Of Melanoma Intervention Targets
Author List
1. Presenting Author: Banu Eskiocak
2. Additional Author: Ian Watson
3. Additional Author: Chang-Jiun Wu
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Melanoma is one of the most aggressive tumors, with metastasis to distant organs correlating with less than 9 months of
median survival. For oncogene-defined melanomas, only selective inhibition of mutant BRAF is approved for late-stage
melanoma treatment. This results in ~80% disease response, but acquired drug resistance always develops, which raises the
need for additional therapeutic strategies. To help address these needs, we are combining genome-wide RNAi screens in
metastatic pigmented melanoma cells, with genome-wide copy number analyses of human melanoma samples, in order to
isolate gene products responsible for the bypass of normal proliferation and survival restraints during melanomagenesis.
Methods
A genome-wide RNAi screen using an arrayed siRNA library targeting ~21,000 genes identified 132 genes, that when
depleted, significantly decreased viability of MNT1 cells. In parallel, array comparative genomic hybridization (aCGH)
analyses of 78 human melanoma tumor specimens revealed that 35 of those 132 genes had significant copy number gains
in disease. Furthermore, expression profiles from matched tumor samples revealed that 18 of these 35 genes were
overexpressed in cancer.
Results
The resulting gene cohort contained the known melanoma oncogenes BRAF, MITF and GOLPH3. In addition the cohort
contains novel genes with similar potencies as these oncogenes and are involved in biological processes that include lipid
metabolism, vesicle transport, microtubule dynamics and signal transduction. When depleted, the majority of these genes
significantly decreased viability in seventeen different melanoma cell lines but not in noncancerous human epithelial cells.
Clustering analysis of this data revealed a collection of targets with activity that correlates with BRAF mutation status.
Additionally, depletion of another set of targets resulted in lethality regardless of BRAF mutation status. Current treatment
efforts are focused on the inhibition of mutant BRAF, which is found in approximately 50-70% of cases, however no
targeted therapies have been identified for the remaining cases.
Conclusion
Here, we identified a group of novel targets with potential therapeutic indications in melanoma regardless of BRAF
mutation status. Furthermore, our studies identified SOX10 as a potential copy number driven oncogene. Interestingly
SOX10 has long been used as a melanoma diagnostic marker, but the evidence of its oncogenic function had been lacking.
Ongoing studies are focused on functional and mechanistic elaboration and pharmacological validation of these genes in
preclinical models.
Financial Disclosure (Banu Eskiocak)
No
FDA Disclosure
Cleared:Yes
Keywords
melanoma
RNAi screen
oncogene
transcription factor
Abstract ID: 309
A Longitudinal Study On Black, Caucasian, And Latino Mens'''''''''''''''''''''''''''''''' Perceptions, Physical And
Psychologic Responses To The Cancer Caregiving Experience
Author List
1. Presenting Author: Guadalupe Palos
2. Additional Author: Javier Valenzuela
3. Additional Author: David Flores
4. Additional Author: Kai Ping Liao
5. Additional Author: Katherine Gilmore
6. Additional Author: Araceli Garcia-Gonzalez
7. Additional Author: Lucy Balderas
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Research examining the experience of male cancer caregivers is sparse, particularly for Latino or Black men. It is unclear if
there are ethnic differences in the meaning of the caregiving experience. It is even more unclear if the psychological and
physical symptoms differ among ethnic men. Here we describe ethnic similarities and differences in the patterns of
menâ€™s perceptions, as well as their physical or psychological responses towards being the primary caregiver of a cancer
patient.
Methods
Data for this sub-analysis on 28 Black, Caucasian, and Latino men were drawn from a larger study to examine how
caregiversâ€™ (distress, sad) and physical (sleep disturbances, fatigue) were affected when caring for a patient with
advanced cancer. We used a longitudinal mixed-method design to identify patients diagnosed with an advanced solid tumor
and their primary caregivers from public hospitals in Texas. Patients were recruited before beginning their treatment
regimen and followed over the treatment cycle (18-20 weeks). Data collection occurred before, during, and after a
treatment regimen. Qualitative interviews were conducted with the men before and after the study. Instruments used to
evaluate symptoms, function, and interference included the M D Anderson Symptom Inventory and the MOS SF-12.
Descriptive statistics were used to describe caregiver/caregiving traits, socio-demographic, and patients' clinical
characteristics. Major themes from the interviews were identified and analyzed using a phenomenological approach.
Results
The majority of the study sample were Latino, married, younger, and well-educated. Over 50% of the caregivers were a
family member, lived with the patient, and provided care >20 hrs/wk. Caregivers reported distress and sadness as the most
severe psychologic symptoms at all time points. Disturbed sleep was more severe during treatment while fatigue was
greater after treatment. Men reported greater interference with their mood and activity. Major themes identified included
fighting the cancer, being resourceful, asking for help, and doing the right thing. Uncertainty of the future and dealing with
the health care system were identified as unfavorable aspects of caregiving.
Conclusion
Perceptions of Black, Caucasian, and Latino men about their caregiver experience were more similar than different. All
ethnic groups reported resourcefulness as their primary source of strength (coping strategy). In the interviews men spoke of
experiencing greater levels symptom severity than documented in the questionnaires. These findings have implications for
developing gender and culturally-specific interventions based on the strengths and obstacles reported by this group of
ethnic male caregivers. Ethnic men who reported positive experiences also expressed experiencing less severe psychologic
and physical symptoms.
Financial Disclosure (Guadalupe Palos)
No
FDA Disclosure
Cleared:Yes
Keywords
symptom burden
men
cargivers
underserved patients
Abstract ID: 310
Design And Synthesis Of Chemopreventives Of Prostate Cancer Based On 6-Shogaol
Author List
1. Presenting Author: Eric Silver
2. Additional Author: Achinto Saha
3. Additional Author: John Digiovanni
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Prostate cancer is predicted to affect 1 in 6 men in the Western world. Prostate cancers also tend to be slow growing,
making them especially apt for chemoprevention. In the search for new chemotherapeutics and chemopreventives in recent
years, there has been a push to isolate and characterize the active compounds in many folk medicines and remedies based
on local flora. In particular, Chinese ginger root (Zingiber officinale Roscoe) stands out as a particularly
intriguing source of compounds; it has been proposed to have inter alia anti-inflammation, antioxdiation,
anti-diarrhea, anti-fouling and anti-cancer activity. 6-Shogaol is a compound found in ginger which has demonstrated
in vitro cytotoxicity against a variety of cancer lines, as well as exhibiting in vivo efficacy against
cancer, showing greater cytotoxicity than its hydrated precursor, 6-Gingerol.
Methods
A library of compounds based on 6-Shogaol will be synthesized in order to increase the efficacy of the compound with
regard to inhibition of hyperproliferation in three prostate cancer cell lines: PC-3, DU-145 and LNCap. These compounds
will then be used to probe further the mechanism of anti-tumorigenesis induced by 6-shogaol; it is hoped that these new
compounds will also lead to improvements in therapeutic efficacy. The compounds will be characterized and their
cytotoxicity will be evaluated by MTT assay. Furthermore, cell signaling will be evaluated through Western blot analysis.
Results
A wide variety of compounds were synthesized by altering the nucleophilic aldol partner (zingerone) and the electrophilic
aldol partner to produce compounds of differing lipophilicity, susceptibility to nucleophilic attack and hydrogen bonding
donating ability. The compounds were evaluated by MTT assay, yielding a â€œhitâ€• in compound ESS_220. In addition,
through investigation of anti-inflammatory pathways, it was determined that 6-shogaol inhibits the activation of Stat3 by
inflammation signaling.
Conclusion
In summary, a library of 6-shogaol derivatives was synthesized and characterized. Promising results were seen in the
ability of these compounds to inhibit the proliferation of prostate cancer cells. The mechanism of anti-tumorigenesis of
6-shogaol was further elucidated to include the Stat3 pathway.
Financial Disclosure (Eric Silver)
No
FDA Disclosure
Cleared:Yes
Keywords
Prostate cancer
6-Shogaol
Chemopreventive
Natural products
Abstract ID: 311
Oxidation Of Acetate In Human Orthotopic Glioblastoma Tumor Model Is Reminiscent Of Normal Astrocytes
Author List
1. Additional Author: Tomoyuki Mashimo
2. Additional Author: Kumar Pichumani
3. Additional Author: Vamsidhara Vemireddy
4. Additional Author: Kimmo Hatanpaa
5. Additional Author: Daniel Sutherland
7. Additional Author: Juan Pascual
11. Presenting Author: Robert Bachoo
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
The prognosis for patients diagnosed with glioblastoma (GBM) remains abysmal despite aggressive multimodal therapy,
including surgery, radiation and chemotherapy. The cellular origins of this deadly tumor also remain controversial;
postulated origins include either neural stem cells, or mature astrocytes. Taking advantage of the fact that only mature
astrocytes in the adult mammalian brain have the ability to utilize acetate, using our recently described human orthotopic
mouse (HOT) model, we directly tested whether GBM cells can metabolize [1,2-13C]acetate.
Methods
Freshly resected GBM specimens were gently dissociated with papain and 50K primary GBM cells were stereotactically
injected into 6-week-old NOD/SCID mouse brain. Metabolic tracer studies were performed 8â€“10 weeks after
implantation of GBM cells when the mice typically developed neurological symptoms. Awake mice were intravenously
infused with [1,6-13C]glucose plus [1,2-13C]acetate (99% enrichment) for 150 min. Under
deep anesthesia and during cold saline perfusion, the tumor and nontumor-bearing brain regions were rapidly dissected and
freeze-clamped. About 200 mg of tissue were obtained from each tumor. Protonâ€“decoupled 13C NMR
spectra of tissue extracts were acquired at (600 MHz) with 2H field-frequency lock.
Results
Co-infusion of [1,6-13C]glucose plus [1,2-13C]acetate will generate characteristic labeling
patterns in intermediates of the citric acid cycle that arise exclusively from oxidation of either acetate or glucose. For
example, the doublet due to J45 in glutamate or the quartet due to J34 and J45 can
only be generated from oxidation of [1,2-13C]acetate. High-quality 13C spectra were obtained.
As expected, 13C enrichment was detected in normal brain in glutamate, glutamine and GABA indicating
rapid turnover of these metabolite pools, and the 13C labeling pattern indicated oxidation of glucose in
preference to acetate. Enriched glutamate and glutamine were observed in tumor but little GABA was detected. Multiplets
characteristic of mitochondrial oxidation of both glucose and acetate were detected in GBM. However, unlike normal
brain, acetate is oxidized in preference to glucose in the tumor. 
Conclusion
In this model of human orthotopic transplanted glioma, both normal brain and tumor oxidized acetate and glucose in the
citric acid cycle. The preference for oxidation of acetate in the glioma is consistent with the hypothesis that mature
astrocytes may be the GBM cell of origin. Remarkably, this result would imply that despite the marked phenotypic and
molecular changes that astrocytes undergo during process of malignant transformation, glial cell metabolism remains
resilient to change in substrate preference. Direct detection of acetate oxidation may serve as a diagnostic marker for GBM.
Financial Disclosure (Robert Bachoo)
No
FDA Disclosure
Cleared:Yes
Keywords
glioma
metabolism
nuclear magnetic resonance
brain
Abstract ID: 312
Cultivando La Salud
Author List
1. Presenting Author: Christina Brito
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Cultivando la Salud: Breast and Cervical Cancer Program (CLS), a program of the National Center for Farmworker Health
is one of only a few evidence-based breast and cervical cancer screening programs designed for underserved, low-income
Hispanic women. The CLS Program utilizes the Community Health Worker (CHW) model to effectively conduct
community outreach and includes a manual for program adopters and implementers; a CHW training curriculum; a
bilingual low literacy flipchart; a Spanish-language video; and a teaching guide for CHWs. The program and educational
materials are culturally and linguistically appropriate and have been developed to address the needs of Hispanic women.
Methods
CLS has been implemented in Hays County with a target population comprised of women who are under and uninsured,
low income, Hispanic, over 20 years of age, are geographically and culturally isolated, demonstrate low health literacy
skills and have a rate of invasive cervical cancer that is significantly higher than that for the state. The overall goal of
CLS-Hays is to increase the rate of age appropriate cervical cancer screening among low-income Hispanic women in Hays
County and increase the implementation of outreach and education by CHWs on breast and cervical cancer. CHWs conduct
door-to-door outreach and a public outreach campaign to deliver cervical cancer information and brochures to the target
population. During the public outreach campaign, CHWs collaborate with non-traditional partners such as local discount
stores, schools, banks, churches, subsidized housing, community grocery stores, flea markets, hair salons, and
Laundromats. The purpose of both outreach strategies is to encourage women to participate in a one-on-one or group CLS
sessions. The CHWs utilize the various CLS educational tools to provide the educational session. Following the education,
the CHWs make referrals to local providers delivering low-cost or free Pap and Mammography services; provide assistance
with appointments, conduct reminder calls, and follow-up.
Results
In the first three quarters of program implementation, the program has completed outreach with 3,984 women, provided an
educational session to 904 women, and made 608 referrals for Pap screening.
Conclusion
The CHW model of intervention delivery has been effective in outreaching to the target population comprised of women
who rarely or never access medical care. Because CHWs are natural leaders in their communities, this model is a culturally
appropriate strategy for overcoming the many barriers to early detection screening faced by low income Hispanic women
in Hays County.
Financial Disclosure (Christina Brito)
No
FDA Disclosure
Cleared:Yes
Keywords
CLS
Hays County
NCFH
CHW
Abstract ID: 313
Texas Colon Cancer Screening, Training, Education & Prevention (Texas C-STEP): A 1-Year Update
Author List
1. Presenting Author: Jane Bolin
2. Additional Author: David McClellan
4. Additional Author: John Simmons
5. Additional Author: Janet Helduser
6. Additional Author: Christine Pinones
7. Additional Author: Phillip Nash
8. Additional Author: Nick Edwardson
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Introduction: Colorectal cancer (CRC) is the second leading cause
of cancer-related mortality in the United States. Five rural counties in the Brazos Valley (BV) region of Texas had CRC
rates higher than the state average. In September, 2011, the Cancer Prevention and Research Institute of Texas (CPRIT)
provided a $2.75 million award to the Texas A&M Health Science Center to increase the number of accessible, affordable
screenings for low-income and underserved residents through: training of family medicine residents; an extensive and
innovative referral network; and use of community health workers for outreach, navigation and follow-up.
Purpose: This presentation describes the one-year progress of this innovative program: Texas C-STEP
(Texas Colon Cancer Screening, Training, Education & Prevention). We include first year clinical findings, methods used
to expand the referral network, strategies for educating professionals and numbers reached, and use of community health
workers to educate and create awareness. 
Methods
Methods: The Family Medicine Residency program at Texas A&M Physicians Family
Medicine Center serves as home base for Texas C-STEP. Capacity for conducting CRC screenings was enhanced by
equipment upgrades, a training simulator, and expansion of the CRC curriculum used in the family medicine residency
program. Referrals for screening came from local agencies, FQHCs, providers and self-referral. Community health
workers/promotores were trained and included in outreach, education, intake, monitoring and follow-up activities. A
customized database was developed to track patient progress.
Results
Results: Preliminary nine-month data reveal that 273 people received CRC screening, 75% of
those had not had a previous colonoscopy. Ninety-four procedures produced abnormal results and CRC precursors or
cancers were detected for 77 patients. The program served 24% Black, 26% Hispanic, and 50% all other race/ethnicities.
Over three thousand people were reached indirectly, almost 1200 directly. One hundred and sixteen professionals received
direct training. Quality control measures including cecal intubation rate, adequate withdrawal time, and adenoma detection
rate were met or exceeded. Complete year 1 results will be available 8/31/2012.
Conclusion
Significance/Conclusion: C-STEP is rapidly increasing the numbers of patients screened for
CRC; numbers of family medicine physicians trained to conduct colonoscopy screenings; and number of CHWs who serve
as patient navigators. The program will serve as a national model for translating colon cancer prevention, screening and
education services into family medicine residency training. Identifying barriers to screening and implementing appropriate
interventions improve colorectal cancer screening rates. Acknowledgement: Funded by CPRIT
grant #PP110176
Financial Disclosure (Jane Bolin)
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal Cancer
Screening
CHW/Promotores
Graduate Education
Abstract ID: 314
Salud San Antonio! A Clinical And Health Education Collaborative For Cancer Screening
Author List
1. Presenting Author: Cynthia Mojica
3. Additional Author: Yuanyuan Liang
4. Additional Author: Christina Carmona
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Cancer is expected to be the No. 1 cause of death in the U.S. and Texas within a decade. Despite effective screening tests,
40% of breast cancers, 36% of cervical cancers, and 54% of colorectal cancers in Texas are detected at an advanced stage
of disease, with Latinos typically experiencing a disproportionate burden of the disease. 
Salud San Antonio! A Clinical and Health Education Collaborative for Cancer Screening (SSA) is a comprehensive
evidence-based cancer prevention services program that has partnered with three San Antonio, Texas community
organizations and a federally qualified health center (FQHC). The program will offer community outreach, clinic in-reach,
education, no-cost cancer screening tests, and navigation support for appointment scheduling, screening/diagnostic
follow-up, and cancer treatment. The educational program and health care navigation will be delivered by bilingual,
bicultural promotores and cancer screening and diagnostic services will be provided by the FQHC. Transportation vouchers
and monetary incentives will also be provided to individuals who participate in the program.
Methods
Promotores will recruit eligible Latino men and women living in 10 zip codes on the cityâ€™s West and South sides. City
officials have designated these zip codes, with 82% Latinos and a median income of less than $27,000, as high-risk areas
for ongoing public health problems. Promotores will conduct clinic in-reach and community outreach to recruit participants
for small group educational sessions on cancer risk factors, screening tests, and early detection. Knowledge will be
measured using surveys and all participants will be referred to our partnering FQHC for no-cost breast, cervical, or
colorectal cancer screening tests. To facilitate communication and data collection, promotores will be equipped with iPads
from Apple Inc. that have wireless access to e-mail, Internet, calendars, and global positioning systems. Outcome data on
screening status will be obtained from medical record reviews.
Results
Promotores will reach 12,000 (4,000 per year) Latino men and women through community outreach and clinic in-reach
efforts. Navigation support by promotores is expected to result in 3,600 (1,200 per year) participants screened for either
breast, cervical or colorectal cancer.
Conclusion
Salud San Antonio! is currently recruiting participants.
Financial Disclosure (Cynthia Mojica)
No
FDA Disclosure
Cleared:Yes
Keywords
evidence-based intervention
cancer screening
promotores
latinos
Abstract ID: 315
Human Papilloma Virus Knowledge And Vaccine Acceptability Among Hispanic Mothers Enrolled In The Entre
Madre E Hija Program
Author List
1. Presenting Author: Deborah Parra-Medina
3. Additional Author: Cynthia Mojica
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Women in Texasâ€™ predominantly Hispanic Lower Rio Grande Valley experience higher incidence and mortality from
cervical cancer compared to the nation. Human papillomavirus (HPV) is the causal agent for cervical cancer. The HPV
vaccine prevents the human papilloma virus and is recommended for women (ages 26 and older) and girls (ages 11 and
older) to help prevent cervical cancer. A smaller proportion of Texas Hispanic girls (ages 13-17) receive â‰¥ 1 dose of the
HPV vaccine compared to Hispanic girls nationally (40% vs. 45.5%) and fewer complete the vaccine series (â‰¥ 3 doses;
23.4% vs. 45.5%). This falls short of the Healthy People 2020 target of 80% of girls (ages 13-15) receiving â‰¥ 3 doses.
Methods
Entre Madre e Hija is a cervical cancer prevention program designed to increase cancer knowledge and
promote HPV immunization and cervical cancer screening. The program is delivered by promotoras and student peer
educators to mothers and their daughters 11-17 years of age in the LRGV. Baseline knowledge is assessed using
interviewer administered surveys before participation in health education sessions for both mothers and daughters. We
conducted a preliminary univariate analyses of HPV knowledge and HPV vaccine acceptability at baseline for Hispanic
mothers currently enrolled in the program (n = 115).
Results
Results of mothersâ€™ HPV knowledge showed: 94.8% believed HPV is detected through a Pap test, 80% believed HPV
is cured with antibiotics, 70.4% believed condoms protect a person from HPV, and 92% believed HPV affects a
womanâ€™s ability to get pregnant. Results of mothersâ€™ HPV vaccine acceptability showed: 47.8% agreed the vaccine
is safe, 13.9% agreed getting the vaccine encourages girlsâ€™ to become sexually active, and 83.5% agreed they would
vaccinate their daughter if their daughterâ€™s doctor recommended it.
Conclusion
Knowledge gaps exist among mothers about how HPV is detected, cured, prevented, and its effects on the body. Almost
half of mothers believed the HPV vaccine to be safe and would vaccinate their daughter if a doctor recommended it.
The Entre Madre e Hija education program is designed to address knowledge gaps identified. To increase
provider recommendations for HPV immunization, additional strategies that target the health-care system are warranted.
Financial Disclosure (Deborah Parra-Medina)
No
FDA Disclosure
Cleared:Yes
Keywords
HPV Vaccine
Hispanics
health education
promotoras
Abstract ID: 316
A Phase 2 Study Of Carboplatin And Docetaxel Followed By Epstein-Barr Virus Specific Cytotoxic T Lymphocytes
For Refractory/Relapsed EBV-Positive Nasopharyngeal Carcinoma
Author List
2. Additional Author: Bonnie Glisson
3. Additional Author: Hao Liu
4. Additional Author: Cynthia Herzog
5. Additional Author: Adrian Gee
10. Presenting Author: Chrystal Louis
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Nasopharyngeal carcinoma (NPC) arises from epithelial cells in the nasopharynx and differs from other head and neck
carcinomas as almost all NPC nonkeratinizing and undifferentiated tumors are associated with Epstein Barr virus (EBV)
infection. Historically, patients with limited local disease have a good overall prognosis when treated with intensity
modulated radiotherapy. However, those with advanced stage disease have 5-year survival rates as low as 40% and those
with metastatic disease at the time of initial diagnosis have median survival of less than 1 year. Due to the poor prognosis
seen in patients with advanced stage, relapsed/refractory disease and the strong association with EBV, the use of adoptive
immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) is an attractive therapeutic option. We and other
groups have shown that the administration of EBV-CTLs to patients with advanced stage NPC is feasible, safe and results
in significant anti-tumor activity. While complete responses were obtained, patients with bulky disease were resistant to
EBV-CTL immunotherapy. We propose that efficacy of CTL immunotherapy can be improved in patients with
relapsed/refractory NPC by using re-induction chemotherapy to decrease the tumor burden prior to adoptive transfer of
EBV-CTLs.
Methods
The primary objective of this Phase II non-randomized study is to determine the overall response rate in patients with
relapsed/refractory, advanced stage EBV-positive NPC after treatment with docetaxel and carboplatin followed by
immunotherapy with autologous EBV-CTLs.
Results
To date, 11 patients with relapsed/refractory NPC have been treated within the Texas Medical Center. Patients have
received a median of 5 cycles of chemotherapy (range: 2 â€“ 6 cycles) followed by 1 autologous EBV-CTL infusion
(range: 0 â€“ 4 infusions). There have been no severe or unanticipated toxicities. For the 7 patients who completed
chemo-immunotherapy, the overall response rate is 57% with 2 complete responses, 1 partial response, and 1 with stable
disease. Correlative studies to analyze changes in EBV-specific immune responses post chemo-immunotherapy are in
progress.
Conclusion
Treatment of relapsed/refractory EBV-positive NPC with chemo-immunotherapy using docetaxel, carboplatin and
EBV-CTL appears safe and has resulted in anti-tumor activity including complete responses. These encouraging results
warrant completion of this current study and further exploration of viral and non-viral tumor antigens that could be used as
new immunotherapeutic targets for NPC.
Financial Disclosure (Chrystal Louis)
No
FDA Disclosure
Cleared:Yes
Keywords
nasopharyngeal carcinoma
EBV
cytotoxic T cells (CTLs)
chemo-immunotherapy
Abstract ID: 317
Colorectal Cancer Screening In A Family Medicine Residency Program
Author List
1. Presenting Author: David McClellan
2. Additional Author: Jane Bolin
3. Additional Author: John Simmons
4. Additional Author: Robert Pope
5. Additional Author: Ryan Loyd
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Background: The Centers for Disease Control estimates that at least 60% of deaths due to
colorectal cancer could be prevented if everyone over the age of 50 were screened for colorectal cancer. Barriers to
colonoscopy include cost, fear, transportation, and medical mistrust. Wilkins et al (2009) demonstrated that colonoscopies
performed by primary care physicians have quality, safety, and efficacy indicators that are comparable to those
recommended by the American Society of Gastroenterologists. 
 
Purpose: The purpose of this paper is to describe the principle components of a colonoscopy training
curriculum in a family medicine residency program. Colon Cancer Screening, Training, Education and Prevention (Texas
C-STEP) is a three-year project at the Texas A &M Health Science Center funded by the Cancer Prevention and Research
Institute of Texas (CPRIT). It aims to increase the number of low-income, rural and underinsured individuals in the Brazos
Valley region of Texas who receive colorectal cancer screening at the Texas A&M Physicians Family Medicine Clinic
(FMC), while increasing the number of colonoscopy-trained family medicine physicians through its residency program.
Methods
Methods: The FMCâ€™s capacity for conducting colon cancer screening was enhanced by the
purchase of new endoscopes, software and a training simulator. A curriculum was developed that will reach approximately
43 residents during their 3-year residency. Key components of the 18-month Texas A&M Family Medicine Residency
Colon Cancer Training Curriculum (repeated twice during residency) include a pre- and post-test on colorectal cancer
knowledge, simulation training, and didactic lectures on screening guidelines and risk assessment, in addition to procedural
techniques.
Results
Results: In the first 9 months of the project, 24 residents received didactic training and
participated in hands-on clinical experiences for colonoscopy training. Two hundred and seventy-three people received
CRC screening, 75% of those had not had a previous colonoscopy. Highlights of the training curriculum will be discussed.
Conclusion
Significance/Conclusion: Training family medicine residents to perform colonoscopy has the
potential to significantly improve screening rates for many low-income and underserved Texans by eliminating inadequate
training. Furthermore, incorporating colonoscopy into the family practice setting has the potential to reduce barriers that
include cost, access, and medical mistrust. 
 
Acknowledgement: Funded by grant #PP110176 from the Cancer Prevention and Research Institute of
Texas. 
Financial Disclosure (David McClellan)
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal Cancer
Family Resident Training
Screening
Education
Abstract ID: 319
Comparison Of Antivascular Effects Of Novel Vascular Disrupting Agents In Breast Cancer Using Dynamic
Bioluminescence Imaging
Author List
1. Presenting Author: Li Liu
2. Additional Author: Jennifer Magnusson
3. Additional Author: Ralph Mason
4. Additional Author: Mary Trawick
5. Additional Author: Kevin Pinney
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Development of neovasculature is critical for tumor growth, survival, and metastasis, and therefore vascular disrupting
agents (VDAs) offer a powerful potential therapy (Integr. Biol. 3, 375-387 (2011)). In
developing any new drug, non-invasive assays of efficacy provide vital insight into activity with respect to dosing and
pharmacodynamics of action. We have previously demonstrated the utility of dynamic bioluminescence imaging (BLI) to
evaluate VDAs such as combretastatin A-4 phosphate (CA4P) (FASEB J.
22, 2445-2451 (2008)) and we have now applied this approach to promising benzosuberene-based
agents, KGP265 and KGP321, and compare the effects of these two drugs with
CA4P in a breast mammary fat pad tumor model.
Methods
MDA-MB-231-luc breast tumors were implanted in female athymic nude mice. Drug dose escalation ranged from 5 mg/kg
to 40 mg/kg by IP injection. KGP265, KGP321 and CA4P (120
mg/kg) effects were assessed at baseline, 2, 4, 24 and 48 hrs after injection. Fresh D-luciferin was administered
at each time point. As a control, additional tumor bearing mice were injected with the same volume of DMSO/saline or
saline.
Results
Dynamic BLI revealed significant antivascular effects upon treatment with KGP265. Dose escalation
indicated that higher doses produced more effective vascular shutdown, and a dose of 7.5 mg/kg
KGP265 appeared optimal, being effective while causing little toxicity. Administration of
KGP265 produced significantly decreased and delayed light emission. BLI signal was reduced by 99%
at 4 hours compared to baseline. At 24 hours post treatment there was very little recovery of the light emission. At doses
above 10 mg/kg, there were some indications of potential toxicity by 48 hrs. KGP321 (30 mg/kg)
showed less effect when compared to KGP265; the BLI signal was reduced by 79% at 2 hours compared
to baseline. Further reduction was seen at 4 hours indicating progressive vascular disruption. At 24 hours post treatment
there was some recovery of the light emission. Light emission was highly consistent under baseline conditions with
reproducible kinetics and intensities. In vivo observations were confirmed by post mortem histology.
Conclusion
The results indicate that KGP265 and KGP321 cause significant vascular disruption.
When compared to CA4P, KGP265 and KGP321 require a lower
dose to achieve similar imaging results (CA4P optimal dose 120 mg/kg, KGP265
optimal dose 7.5 mg/kg, and KGP321 optimal dose 30 mg/kg) suggesting enhanced efficacy, which we
are continuing to explore.
Financial Disclosure (Li Liu)
No
FDA Disclosure
Cleared:Yes
Keywords
Dynamic Bioluminescence Imaging
Vascular Disrupting Agents
Benzosuberene-based Anticancer Agents
Tumor Vasculature
Abstract ID: 321
Increasing Pap Test Rates Among Hispanic Women In Bexar County
Author List
1. Presenting Author: Roberto Villarreal
2. Additional Author: Leah Trevino
3. Additional Author: Laura Fornos
4. Additional Author: Tiana Lucas
5. Additional Author: Virginia Mika
6. Additional Author: Kathleen Urbansky
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The proportion of women age 18 or over at risk for cervical cancer in the US is 18.7%. In San Antonio, it is much larger
(60%) for a subpopulation of Hispanic women. University Health System (UHS) is a safety-net health system serving
Bexar County, Texas. UHS operates CareLink, a financial assistance program for uninsured county residents. Our target
population was comprised of high-risk women enrolled in CareLink. At the end of 2009, 33,000 (67%) women were
neither current for Pap tests nor actively obtaining appointments. To reduce the impact of cervical cancer, we developed a
culturally competent, evidence-based program using the A Su Salud (To your Health) model of prevention.
Methods
A Su Salud uses well understood Hispanic based health promotion techniques. Qualitative research served as the basis for
targeted messaging for women out of compliance. Results from focus groups developed program content. Pap test status
determined frequency of messaging. Program coordinators created monthly, bilingual newsletters, televised segments and
PSAs. We maintained a Facebook page containing posts, video, visual media, links to local resources or events and
requests for personal input. Program components asked women to call â€œClaudiaâ€•, a bilingual contact person. Claudia
is a pseudonym for multiple staff that embody the Mexican American cultural value of personalized social communication,
or personalismo.
Results
Women were knowledgeable about Pap guidelines; however, when asked about causes of cervical cancer their answers
reflected misconceptions. Women said their providers did not discuss Pap information and therefore, felt less empowered
to ask questions. We distributed13,964 newsletters to 5 community health care clinics, 10 preventive health clinics and 5
CareLink offices. These newsletters reached an estimated 2,500 to 6,500 people. Twelve television segments were aired on
the Spanish television network, Univision. As of 2012, 639 unique viewers accessed our PSAs through the internet.
â€œClaudiaâ€• contacted 1,033 women about Pap tests and scheduling their appointments. Of those women, 139 scheduled
an appointment for a Pap test; the study team confirmed 47. At baseline, our cohortâ€™s (n=32,807) screening rate was
33% (n=10,847). Through this program, we increased the Pap test rate to 42% (n=13,671).
Conclusion
This program increased Pap tests by 9% among Hispanic women enrolled in CareLink. Key elements that promoted the
success of this program included qualitative research to promote targeting for greatest impact and the removal of cultural
barriers through our language-concordant telephone navigator.
Financial Disclosure (Roberto Villarreal)
No
FDA Disclosure
Cleared:Yes
Keywords
Cervical
Prevention
Pap
Hispanic
Abstract ID: 322
Integrating Community Health Workers Into A Colon Cancer Screening Program
Author List
1. Presenting Author: Jane Bolin
2. Additional Author: David McClellan
4. Additional Author: Janet Helduser
6. Additional Author: Julie StJohn
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Introduction: Transportation, cost, and medical and cultural mistrust are among the barriers to
cancer screenings. The use of Community Health Workers/Promotores (CHW/Ps) is considered by many to be an effective
means of reducing barriers, while improving patient care. 
Purpose: This presentation focuses on the tools and processes used to integrate CHW/Ps into a screening
program for colorectal cancer based in a family medicine clinical setting. 
Methods
Methods: Colon Cancer Screening, Training, Education and Prevention (Texas C-STEP) puts
CHW/Ps at the forefront of community outreach and patient care activities as they: (1) utilize culturally-competent
communication skills, (2) act as community liaisons for education, referrals, and outreach, (3) serve as a bridge between
patient and clinical staff, (4) assist patients through the screening process and preparatory visit, and (5) help patients
navigate complex follow-up care and safety-net services.
Results
Results: A collaboration between the Texas A&M Health Science Centerâ€™s Family
Medicine Residency and School of Rural Public Health, Texas C-STEP provided training for 12 CHW/Ps in the 8 core
competencies required for state CHW/P certification, including communication and interpersonal skill training to reduce
cultural barriers between the patient and provider. The CHW/Ps were equipped by Texas C-STEP with tools to assist
patients from initial point of contact, through screening and follow-up. Within the clinic, CHW/Ps also serve as case
managers, tracking patient contacts and education while recording patient information and progress.
Conclusion
Conclusions & Significance: Colorectal cancer is a significant public health problem in the
Brazos Valley and Texas, especially in rural underserved populations. Texas C-STEP has established the tools and
processes to maximize use of CHW/Ps in a colon cancer screening program. 
 
Acknowledgement: Funded by grant #PP110176 from the Cancer Prevention and Research Institute of
Texas. 
Financial Disclosure (Jane Bolin)
No
FDA Disclosure
Cleared:Yes
Keywords
CHW Promotores
Cultural Mistrust
Patient Barriers
Cancer Screening
Abstract ID: 324
The Glutathione Synthesis Inhibitor Buthionine Sulfoximine Synergizes Anti-Myeloma Activity Of Melphalan
Against In Vitro And In Vivo Models Of Multiple Myeloma
Author List
1. Presenting Author: Ashujit Tagde
2. Additional Author: Hardeep Singh
3. Additional Author: Min Kang
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Multiple myeloma (MM) is a debilitating hematological malignancy causing nearly 10,000 deaths per year. It is commonly
treated with the myeloablative doses of melphalan (L-PAM) + stem cell transplantation (SCT). Relapse after SCT is
common. Glutathione (GSH) is an intracellular antioxidant that protects cells against xenobiotics by conjugation. Enhanced
GSH is one known mechanism of L-PAM resistance. Buthionine sulfoximine (BSO) inhibits synthesis of GSH and
enhanced the activity of L-PAM in preclinical and clinical studies of neuroblastoma. We investigated the potential for BSO
to enhance activity of L-PAM against in vitro and in vivo models of multiple myeloma.
Methods
Cytotoxicity of L-PAM (0-50 micro molar) +/- BSO (0-400 micro molar) was assessed in a panel of nine MM cell lines
using the DIMSCAN cytotoxicity assay. Single-strand DNA (ssDNA) damage was measured by F7-26 monoclonal
antibody, apoptosis in vitro and in vivo by TdT labeling (TUNEL), mitochondrial depolarization by JC-1 staining and
caspase activity by immunoblot. Intracellular GSH was determined by HPLC. In vivo activity of BSO + L-PAM was
investigated in the MM.1S, KMS-12-PE, and OPM-2 cell lines grown as subcutaneous xenografts in BNX mice.
Results
BSO (400 micro molar, clinically achievable) significantly depleted intracellular GSH (p<0.05) by 77.8 + 8.1% in
nine MM cell lines. At clinically achievable concentrations (100-400 micro molar), BSO consistently caused 2-4 logs
synergistic enhancement of L-PAM cytotoxicity (combination index < 1) in all MM cell lines in bone marrow hypoxia (5%
O2). BSO + L-PAM induced a significant increase in ssDNA damage (p<0.01), mitochondrial depolarization (p<0.001),
DNA fragmentation (p<0.001), cleavage of caspase-9, caspase-3, and PARP (p<0.05) compared with L-PAM alone. For all
three MM xenograft models BSO alone (125 mg/kg b.i.d) had a minimal anti-tumor activity while L-PAM (10 mg/kg/day)
by itself was moderately active. In contrast, BSO plus L-PAM in all three MM xenografts had a very potent activity
inducing a complete response (CR) in 21/25 mice while 6/25 mice had a maintained complete response (MCR) for >100
days. The combination treatment induced a 2.25 fold increase (p<0.001) in the median event-free survival (EFS) (49.5
days) as compared to L-PAM alone (22 days) and significantly enhanced (p<0.01) the percentage of apoptotic cells in vivo
as compare to single agents and control.
Conclusion
Depletion of GSH with BSO enhanced the activity of L-PAM in MM cell lines in vitro and in xenografts. Combining BSO
with L-PAM warrants clinical testing in recurrent MM.
Financial Disclosure (Ashujit Tagde)
No
FDA Disclosure
Cleared:Yes
Keywords
Multiple Myeloma
Melphalan
buthionine sulfoximine
In vitro and in vivo
Abstract ID: 325
Health Related Quality Of Life Survey Using SF-36 In Breast Cancer Survivors In El Paso
Author List
1. Presenting Author: Zeina Nahleh
2. Additional Author: Cristina Dominguez
3. Additional Author: Tony Khang
4. Additional Author: Aleem Sattar
5. Additional Author: Adolph Ulloa
6. Additional Author: Indika Mallawaarachchi
7. Additional Author: Alok Dwivedi
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
ASL image.jpg
Summary
Introduction
Introduction: Breast Cancer survivors in El Paso include a majority of Hispanics. A higher rate of psychosocial stress,
depression and inappropriate follow up care are reported in Hispanics. This pilot study aims at assessing the Health Related
Quality of Life (QOL) of our breast cancer survivors to better understand their needs after their cancer diagnosis and
treatment.
Methods
Methods: After IRB approval, we recruited consecutive patients seen in the University Breast Care Center (UBCC) over 6
months in 2012 who are within the first 5 years post-diagnosis with Stages I-III breast cancer and on no active
chemotherapy and/or radiation therapy. A questionnaire using the validated health survey SF-36 was used assessing an
8-scale profile of functional health, wellness score, and psychometrically based physical and mental health (Ware JE,
1992). Each scale is scored from 0 to 100 (most favorable). Spanish version was provided. Descriptive statistics were
utilized. A validated two summary scales one for physical health (Physical Component Summary, PCS) and one for mental
health (Mental Component Summary, MCS) was also calculated (Ware JE, 1994).
Results
Results: 67 patients were recruited and all completed the questionnaires, 99% were Hispanics. Mean age 51 years (range
38-84) , 19% of patients were less than 50 years of age. The scores were are as follows: physical functioning 85.0; Role
Functioning- Physical 87.8; Mental Health 61.9; Role Functioning- Emotional 88.3; Bodily Pain 59.7; Vitality 75.2;
General Health 64.0; and Social Functioning 61.0. PCS representing the mean for the SF-36 Physical Health was 47.7, and
the MCS for Mental Health was 40.0, both below the population norm for healthy women; 63% report that physical or
emotional problems interfere with their normal social activities, 36% report having emotional problems with their work or
other daily activities and 44% have difficulty performing their work. The mean PCS and MCS for the following categories:
<50 versus >50 years; chemotherapy versus not; and diagnosis within 1-3 years versus> 3 showed no differences except for
MCS (chemo 49.3 versus no chemo 43.4)
Conclusion
Conclusion: The majority of our Hispanic breast cancer survivors in El Paso appear to have decreased mental and physical
health related QOL which limits normal social functioning. A better Mental Health MCS in favor of those who received
chemotherapy need confirmation in larger studies. Hispanic Breast Cancer survivors in El Paso would benefit significantly
from survivorship care programs designed to address their unmet needs.
Financial Disclosure (Zeina Nahleh)
No
FDA Disclosure
Cleared:Yes
Keywords
Breast cancer
Survivor
Hispanic
quality of life
Abstract ID: 326
Testing A Model For Mothersâ€™ Intention To Initiate The HPV Vaccine Series For Their Daughter (ages 11-17)
Author List
1. Presenting Author: Daisy Morales-Campos
2. Additional Author: Daniel Sass
3. Additional Author: Deborah Parra-Medina
4. Additional Author: Cynthia Mojica
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
HPV Model 1.jpg
Summary
N/A
Introduction
Women in Texasâ€™ predominantly Hispanic Lower Rio Grande Valley (LRGV) experience higher incidence and
mortality from cervical cancer compared to the nation. Human papillomavirus (HPV) is the causal agent for cervical
cancer. The HPV vaccine prevents the virus and is recommended for women (ages 26 and older) and girls (ages 11 and
older) to help prevent cervical cancer. A smaller proportion of Texas Hispanic girls (ages 13-17) receive â‰¥1 dose HPV
vaccine compared to Hispanic girls nationally (40% vs. 45.5%) and fewer complete the vaccine series (â‰¥3 doses; 23.4%
vs. 45.5%). This falls well short of the Healthy People 2020 target of 80% of girls (ages 13-15) receiving â‰¥3 doses. In
the literature, determinants from the theories of HBM and TRA have been used to predict motherâ€™s intention to
vaccinate oneâ€™s daughter, but a gap still exists regarding the development and evaluation of theoretically grounded
interventions designed to increase HPV vaccine initiation and completion.
Methods
Using baseline data from Hispanic mothers (n = 209) with daughters ages 11-17 that have never been vaccinated for HPV
and enrolled in a health education program to promote HPV vaccination in the LRGV, we tested a model based on the
theories of HBM and TRA that might predict mothersâ€™ intention to vaccinate their daughters. It included the
determinants of perceived threat, HPV vaccine attitudes, benefits and barriers, self efficacy, subjective norms and
communication openness as factors in the model. We used structural equation modeling to determine if the model fit and
what model aspects were in conflict with the data.
Results
Preliminary results indicate that the hypothesized theoretical model was not supported by the data (df = 848; Ï‡2 =
1222.27; P < .001; root mean square error for approximation = 0.046; comparative fit Index = 0.902; Tuckerâ€“Lewis
index = 0.896). Further analyses will be conducted to modify the original model in order to produce a model with a better
fit.
Conclusion
Interventions aimed at increasing uptake of the HPV vaccine series in the LRGV should consider determinants that affect
intentions to initiate the series among Hispanic mothers.
Financial Disclosure (Daisy Morales-Campos)
No
FDA Disclosure
Cleared:Yes
Keywords
HPV vaccine
Hispanics
Border
Adolescents
Abstract ID: 328
A Su Salud Colorectal Cancer Education, Outreach, And Health Promotion Program
Author List
2. Additional Author: Yamille Silva
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Colorectal cancer is the 2nd leading cause of death and the 3rd most common cancer in adult men and women in the US.
Adult men and women 50 years and older in Bexar County demonstrate an incidence rate of 36.9 per 100,000 in 2009, and
a mortality rate of 15 per 100,000. As a result, UHS committed to increase screening rates by 10% in Bexar County during
the two year span of the health promotion program, by using the A Su Salud model, which utilizes mass and small media to
broadcast targeted messages to help the target audience ascend through the Stages of Change. UHS also uses CareLink, a
medical financial assistance program benefiting uninsured patients, to disseminate information.
Methods
Following the A Su Salud model, messages were developed and tailored based on salient themes from 5 bilingual focus
groups of CareLink enrollees to determine the level of knowledge about colorectal cancer, screening and perceived barriers
specific to the community. A pre-survey was conducted June through October 2011 to establish baseline knowledge,
beliefs and perceptions. A cohort of CareLink members (21,583) from July 2011 were chosen to establish the impact of the
program. Process measures include the number of adults 50 years and older reached through public service announcements
(PSAs), newsletters, telephone reminder calls, and CareLink bill inserts beginning November 2011. High risk adults, those
with no evidence of having a colonoscopy in the past 10 years, received a TeleVox reminder call.
Results
Six bilingual PSAs were created, and distributed through 70 television stations, through Facebook and YouTube. These
garnered a total of 117 â€œviewsâ€•. Five newsletters (19,386 copies) were distributed throughout UHSâ€™ network. Fifty
thousand CareLink members were reached through bill inserts. The cohort had a baseline screening rate of 24%, and a total
screening rate of 26% as of February 2012. There were 2,689 calls successfully made by TeleVox in February 2012.
February through March 2012, 36 people called the programâ€™s telephone line, as prompted by the call to action.
Conclusion
As of February 2012, 16% of the adults that received a colonoscopy during the intervention period were part of the high
risk cohort who received a TeleVox reminder call. Although the program is still underway, this demonstrates the A Su
Salud health promotion model can be used to positively impact a community by increasing cancer screening.
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal
Screening
Male
Hispanic
Abstract ID: 329
What Do Texas Cancer Care Providers, Researchers And Residents Have In Common? Current Cancer-Related
Care Information On The CERCIT Website
Author List
1. Presenting Author: Catherine Cooksley
2. Additional Author: Anthony DiNuzzo
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Improving cancer-related care and the well-being of those diagnosed with cancer by integration of research findings into
practice are the focus of Goals 12 and 16 of The Texas Cancer Plan for 2012. The Comparative Effectiveness Research on
Cancer in Texas (CERCIT) project began in August of 2010 and strives to aid in the achievement of these goals through a
comprehensive set of studies following cancer-related care from diagnosis through supportive care. The project is
supported through core components providing research resources, training and dissemination of study findings. The
CERCIT team circulates research findings, training presentations and more to care providers, researchers and all interested
Texans through our website, www.txcercit.org.
Methods
Core principal investigators and collaborators designed our website to be easily navigated and informative to a variety of
audiences. We consult with health education and media specialists to ensure that all materials are understandable and
availability of these resources via our website is widely disseminated. Periodic email messages describing updates are sent
to those who have subscribed to our listserve.
Results
Findings from the CERCIT studies are relayed through links to published manuscripts, opinion editorials (op-eds), reports,
summaries of our latest findings, current cancer information and video-taped presentations. Workshop and conference
materials on methods to conduct comparative effectiveness research as it applies to cancer research are available via links
to PowerPoint presentations and video. Within the past 30 days, when website visitor counting began, over 650 people
have visited our website.
Conclusion
Investigators with this multi-investigator, multi-institutional project have created and actively use the CERCIT website as
one of our dissemination strategies. We provide Texas-specific research findings, the latest cancer-related information and
training tools to care providers, educators, researchers, the general public and the media.
Financial Disclosure (Catherine Cooksley)
No
FDA Disclosure
Cleared:Yes
Keywords
Comparative Effectiveness Research
Cancer-related Care
training
website
Abstract ID: 330
Chemotherapy Resistant, Dormant Glioblastoma Cells Exhibit Persistent Oxidative Metabolism
Author List
1. Additional Author: Tomoyuki Mashimo
2. Additional Author: Kumar Pichumani
3. Additional Author: Vamsidhara Vemireddy
4. Additional Author: Kimmo Hatanpaa
5. Additional Author: Daniel Sutherland
7. Additional Author: Juan Pascual
11. Presenting Author: Elizabeth Maher
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Glioblastoma (GBM) remains an incurable primary brain tumor, with therapeutic gains over past three decades measured
in months. Several next-generation molecularly-targeted therapies have been developed recently; however, there remains
an urgent need to develop methods that can accurately monitor therapeutic response. It is expected that the bioenergetic
demands of growing tumor must exceed that of quiescent or dormant tumors. The traditional use of
18F-fluoro-deoxyglucose (FDG) has been limited in neuro-oncolgy due to high background from normal grey
matter, but limited results indicate that glucose metabolism correlates with tumor viability. We directly tested the
assumption that fast growing GBM will have fundamentally different metabolic profile than proliferation-arrested tumors.
Using an orthotopic mouse model of GBM, we compared oxidation of 13C - enriched glucose in untreated
and temozolamide (TMZ) treated GBM.
Methods
Mouse human orthotopic tumor (HOT) model was produced by isolating tumor cells from freshly resected surgical
specimens from patients and stereotactically injecting them into 6-week-old NOD/SCID mouse brain. After 8 - 10 weeks,
when neurological symptoms were evident, mice were treated with TMZ at clinically-equivalent dose (80 mg/kg x 5 days,
equivalent to one cycle of standard care), or vehicle. Tracer studies were performed 3 days later. After a priming bolus,
awake mice were infused with [U-13C] glucose for 150 min. Mice were then deeply anesthetized and
perfused with ice-cold saline. The tumor and non-tumor-bearing brain regions were rapidly dissected and freeze-clamped.
Protonâ€“decoupled 13C NMR spectra of tissue extracts were acquired at 150 MHz with 2H
field-frequency lock.
Results
Histopathological and biochemical analysis confirmed that TMZ induced a dramatic inhibition of GBM cell proliferation in
tumors treated with TMZ (MiB1, vehicle~65% vs. 6%). High quality 13C NMR spectra were obtained from
extracts of tumors from treated and untreated animals. Extensive 13C labeling was observed in lactate,
alanine, glutamine and glutamate in both groups, consistent with avid metabolism of glucose. The multiplets from tumors
in both groups indicated extensive oxidation of glucose in the citric acid cycle. In fact, the 13C labeling
patterns were virtually identical in both groups.
Conclusion
TMZ dramatically inhibited cell proliferation, as expected. Surprisingly, following TMZ the dormant GBM cells continued
high rates of glucose oxidation in the tumor mass. This observation may in part explain why PET studies have failed to be
prognostic of therapeutic response and raises the possibility that non-glucose substrates may contribute to GBM growth.
Financial Disclosure (Elizabeth Maher)
No
FDA Disclosure
Cleared:Yes
Keywords
glioma
metabolism
nuclear magnetic resonance
temozolomide
Abstract ID: 331
An Integrated Professional Oncology Curriculum For Texas Primary Care Professionals: Improving Care and
Enhancing Quality of Life for Breast, Colon and Prostate Cancer Survivors
Author List
1. Presenting Author: Lewis Foxhall
2. Additional Author: Kendra Woods
3. Additional Author: Therese Bevers
4. Additional Author: Maura Polansky
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
With the shortage of oncologists projected in the 2005 Association of American Medical Colleges Center for Workforce
Studies report and trends in improvement in survival following a cancer diagnosis, there is a clear need for primary care
providers to take an increasing role in the long-term care of cancer survivors. At present, family medicine and internal
medicine physicians and physician assistants (PAs) receive limited formal education in cancer survivorship during their
training. Continuing medical education is essential to develop the necessary clinical competencies to participate in cancer
surveillance, management of long-term treatment sequelae, screening for second malignancies and identifying psychosocial
issues experience by cancer survivors. Given the geographic distance of many Texas communities to major medical
centers, providing such continuing medical education in an online learning format will ensure that access to this instruction
is available to all primary care providers at any time.
Methods
The primary goal of the initiative is to develop an integrated survivorship program to improve clinical competencies of
Texas primary care providers. The program aims to create a comprehensive survivorship curriculum that integrates
instructional material in multiple formats, techniques, and delivery methods to improve clinical competencies in
survivorship care of breast, prostate or colon cancer, since half of all cancer survivors have been diagnosed with these
cancers. This program includes a performance improvement (PI) activity which is designed to fulfill Maintenance of
Certification requirements for physicians. The PI activity involves review of patient data regarding screening for second
primary cancers for survivors.
The course is provided online and by DVD or pen drive, upon request.
Results
The program seeks to improve access to survivorship professional education for Texasâ€™ 18,000 primary care providers,
leading to improved cancer survivor care.
Conclusion
Two comprehensive courses covering Breast Cancer and Colorectal Cancer Survivorship are completed and open for
enrollment online at mdanderson.org/POE. A final module on Prostate Cancer Survivorship will be posted shortly.
Financial Disclosure (Lewis Foxhall)
No
FDA Disclosure
Cleared:Yes
Keywords
Cancer
Survivorship
Professional
Education
Abstract ID: 332
DHHC5, A Protein Palmitoyltransferase, As A Novel Therapeutic Target For Non-Small Cell Lung Cancer
(NSCLC)
Author List
1. Presenting Author: Hui Tian
2. Additional Author: Jui-Yun Lu
3. Additional Author: Kenneth Huffman
4. Additional Author: Ryan Carstens
6. Additional Author: Sandra Hofmann
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Post-translational palmitoylation of intracellular proteins is mediated by protein palmitoyltransferases (PAT) belonging to
the DHHC family, which shares a common catalytic Asp-His-His-Cys (DHHC) motif. According to a genome-wide siRNA
screen scoring for growth suppression in about 50 non-small cell lung cancer (NSCLC) cell lines, DHHC family members
are strikingly over-represented. Among the tested DHHC palmitoyltransferases, knockdown of DHHC5 showed cell
growth inhibition in many cell lines in the initial screen.
Methods
To verify the growth suppression in response to DHHC5 depletion, transient and stable knockdowns of DHHC5 were
undertaken in several cell lines identified in the genome-wide screen (H1299, H2009 and H157) using siRNAs and a
lentiviral shRNA. The gene expression and protein levels of DHHC5 were analyzed by RT-PCR and immunoblotting. The
MTS cell proliferation assay was performed to check the cell growth arrest. To further investigate the possible roles of
DHHC5 in NSCLC, a Tet-On inducible system using TRIPZ shRNA lentiviral delivery was established in the sensitive cell
lines. Rescue experiments involving ectopic plasmid-driven DHHC5 expression are in progress.
Results
The RT-PCR and western blotting results of both transient and stable knockdowns of DHHC5 in the sensitive cell lines
showed efficient knocking down levels; the MTS cell proliferation assay performed over 4 days confirmed the cell growth
arrest ; liquid colony formation assay in the uninduced and induced cell lines showed decreased colony numbers and sizes.
Conclusion
We have been able to show the cell growth arrest phenotype with DHHC5 depletion in the sensitive NSCLC cell lines. As
DHHC5 function is needed for optimal lung cancer cell growth, it will be important to identify physiologically relevant
substrates in order to develop inhibitors of DHHC5 function. Future plans will involve palmitoyl-proteome profiling of
lung cancer cell lines with and without DHHC5 silencing and validation of candidate substrates using available
biochemical assays. The assays to be employed will be similar to those used to identify flotillin-2 as a substrate for
DHHC5 in other cell types in our laboratory.
Financial Disclosure (Hui Tian)
No
FDA Disclosure
Cleared:Yes
Keywords
None
None
None
None
Abstract ID: 334
Bioreductively Activatable Prodrug Conjugates Designed To Target Hypoxic Tumors
Author List
1. Presenting Author: Tracy Strecker
2. Additional Author: Rajendra Tanpure
3. Additional Author: Clinton George
4. Additional Author: David Chaplin
5. Additional Author: Mary Trawick
6. Additional Author: Kevin Pinney
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The discovery of new anticancer therapeutic agents that are both potent and highly selective remains a significant
challenge. Our previous studies have identified the benzosuberenes as a class of small-molecules that have significant
potential for further development. A phenolic benzosuberene derivative (KGP18) and its corresponding
amine congener (KGP156) are remarkably cytotoxic (picomolar and sub-nanomolar, respectively)
against a wide range of human cancer cell lines and demonstrate potent inhibition of tubulin assembly (cell-free assay). To
target tumors selectively versus healthy tissue, KGP18 has been synthesized as bioreductively
activatable prodrug conjugates (BAPCs) designed to facilitate release of the effector drug in regions of hypoxia. Since a
significant number of solid tumors are characterized by extensive regions that are low in oxygen, BAPCs represent a
potentially efficient and effective targeting strategy for tumor hypoxia. Low oxygen levels in tumor tissue result in the
upregulation of a number of reductase enzymes. The BAPCs, which are designed to be inert (non-toxic), are cleaved by
these bioreductive enzymes to release the effector drug (KGP18) in the hypoxic regions of the tumor.
This type of strategy has gained foundational support by the continuing success in human clinic trials of
TH302 (Threshold Pharmaceuticals), which functions in a somewhat related manner.
Methods
(1) A series of BAPCs of KGP18 have been prepared synthetically that incorporate either nitrothiophene
or nitroimidazole-based triggers as the bioreductive portion of the conjugate. (2) The BAPCs are evaluated in human
cancer cells lines for their differential cytotoxicity under anoxic (Coy Chamber) versus normoxic conditions. The results
are expressed as a hypoxic cytotoxicity ratio (HCR) with tirapazamine, a proven compound that is activated under hypoxic
conditions, as the control.
Results
In initial results with epithelial lung carcinoma A549 cells, bioreductively-activatable prodrug KGP292
gave an average GI50 value of 28 Î¼M under normoxic conditions while an eight-hour anaerobic (Coy
Chamber) exposure of KGP292 gave an average GI50 value of 2.8 Î¼M. This resulted in a
promising HCR of 10 [GI50 (normoxic)/GI50 (hypoxic)]. In an analogous experiment in the
same cell line with four-hour anaerobic exposure, KGP304 was active as a bioreductive prodrug
conjugate. The prodrug KGP293 was activated in eight-hour anaerobic exposure with the colorectal
adenocarcinoma cell line HT29. The effector drug (KGP18) itself is potent (GI50=
0.000027 Î¼M) against A549 cells.
Conclusion
BAPCs that incorporate KGP18 as the cytotoxic effector represent a promising strategy for selectively
targeting the tumor microenvironment.
Financial Disclosure (Tracy Strecker)
No
FDA Disclosure
Cleared:Yes
Keywords
benzosuberene-based anticancer agents
targeting tumor hypoxia
bioreductively activatable prodrug conjugates
hypoxic cytotoxicity ratio
Abstract ID: 335
Evaluating Pharmacokinectics And Pharmacodynamics Of Enhanced Tumor Vascular Targeting Antibodies
Author List
1. Additional Author: Srinivas Chiguru
2. Additional Author: Patrick Thomas
3. Additional Author: Ramona Lopez
4. Additional Author: Li Li
5. Additional Author: Li Liu
6. Additional Author: Padmakar Kulkarni
7. Additional Author: Philip Thorpe
8. Presenting Author: Ralph Mason
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Tumor vascular targeting is attractive since local damage may be amplified downstream. Dr. Thorpe previously identified a
unique vascular target in tumors: specifically, exposed phosphatidylserine (PS) on the luminal side of tumor vasculature. A
first generation therapeutic antibody bavituximab [Clin. Cancer Res., 2009, 15, 6871]) is in Phase 2 clinical trials. The goal
of the MIRA is to develop enhanced therapeutic antibodies or antibody fragments with modified pharmacokinetics and the
Imaging Core seeks to evaluate the new agents. Radiolabeled monoclonal antibodies are convenient for biodistribution
studies and increasingly permit tumor imaging by PET or SPECT. We previously demonstrated localization of
radioarsenic-labeled bavituximab to PS in rat tumors using 77 or 74As and found maximal tumor to background after 72 hr
[Clin. Cancer Res. 2008, 14, 1377]. We are now evaluating alternative labeling strategies and developing orthotopic tumor
models.
Methods
We are testing new fully human PS-targeting antibody 1N11 to image mice with orthotopic PC3 prostate tumors.
Bioluminescent imaging provides a convenient method to verify tumor implantation and growth non-invasively. High
resolution ultrasound permits tumor volume estimates and potentially blood flow/perfusion measurements. 1N11 was
directly labeled with iodine-125 (t1/2 =59.4 days) using the Iodogen method. To evaluate uptake of radioiodinated
125I-1N11 in specific tissues, biodistribution studies were performed 24 and 48 hr after intravenous (IV) injection of 50
ÂµCi labeled 1N11. Similar mice were injected with 485 ÂµCi (160 Âµg) 125I-1N11 and SPECT/CT was performed after
24, 48, and 120 hr. As a control, additional tumor bearing mice were injected with 125I-Aurexis. Following imaging,
tumor, blood, and major organs were collected for comparative biodistribution analysis.
Results
After 24 hr 125I-1N11 activity in the blood was 12Â±1%ID/g, whereas uptake in all other tissues, including tumor, was
<6% ID/g except spleen. After 48 hr, 125I-1N11 activity was high in the tumor (1.6Â±0.8%ID/g) and blood
(0.6Â±0.2%ID/g) relative to other tissues. At 120 hrs 125I-1N11 activity was 0.97Â±0.07%ID/g in the tumor and
0.33Â±0.04%ID/g in blood, while 125I-Aurexis uptake was 7.5Â±1.1%ID/g in blood. SPECT clearly showed the vascular
presence of labeled mAbs at early times with progressive accumulation in the tissues. For 1N11 signal was observed in the
lower abdomen consistent with orthotopic prostate tumor uptake.
Conclusion
125I-1N11 showed more rapid vascular clearance and greater tumor uptake than the negative control 125I-Aurexis. We
have demonstrated proof of principle for PK assessment of labeled mAbs as a foundation for examining further agents.
Financial Disclosure (Ralph Mason)
No
FDA Disclosure
Cleared:Yes
Keywords
Vascular Targeting
Pharmacokinectics
Antibodies
SPECT
Abstract ID: 336
Computational Multi-Modal Drug Repurposing Method: A Prostate Cancer Target Case Study
Author List
1. Presenting Author: Sharangdhar Phatak
2. Additional Author: Shuxing Zhang
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
CRPIT_Abstract.jpg
Summary
N/A
Introduction
Drug repurposing against Activated CDC42 kinase 1 (ACK1) may expedite the cost-effective development of
androgen-independent prostate and breast cancer therapeutics. Application of one computational drug discovery method
(uni-modal) is likely to have lower sensitivity i.e. unlikely to identify all possible marketed drugs that may inhibit ACK1.
We hypothesize that a combination of computational methods (multi-modal) and integration of stepwise results will
improve the sensitivity of retrieving ACK1 inhibitors. Here, we present a multi-modal computational approach for drug
repurposing, and one specific application for ACK1 inhibitor discovery. 
Methods
We applied molecular docking, chemical and genomics similarity methods in combination with bipartite-graph
methods to identify potential ACK1 inhibitors. We used two crystal structures of ACK1 and an in-house curated set of
1447 small molecule drugs, to identify the first set of putative inhibitors using the molecular docking method. Here, the
compounds are scored and ranked based on a mathematical function that calculates their shape and charge complementarity
within the protein active site. Next, a network of approved drugs and their corresponding interacting protein targets was
developed from publicly available resources. Next using two-dimensional vector representing chemical features termed
fingerprints, a second set of inhibitors were identified that shared chemical similarity with known non-drug ACK1
inhibitors and whose interacting proteins shared significant (>40%) sequence similarity with ACK1. A third set of
inhibitors were identified by using a metric that calculated similarity between ACK1 and other proteins based on their
shared and unshared number of interacting drugs. A total of 10 drugs were experimentally tested with a proprietary qPCR
based assay. 
Results
Dasatinib (Figure 1), Amodiaquine, Flavoxate, Imatinib and Lapatinib were selected from the molecular docking
approach. Gefitinib (Figure 2), Sorafenib and Sunitinib were selected from stage 2, i.e. using chemical and genomic
similarity based method. Flavopiridol was the only one selected and experimentally tested from the graph-based method.
The identification of Dasatinib, a known ACK1 inhibitor, validated our approach. More importantly, the identification of
previously unreported Sunitinib, Flavopiridol, and Gefitinib (each developed for different protein target and identified from
different computational approaches), as potent (IC50<20uM) ACK1 inhibitors support our argument of using multi-modal
methods for drug repurposing. 
Conclusion
This is likely the first study to offer a multi-modal computational approach in combination with experimental
validation for drug repurposing against ACK1. The authors believe that this approach can be easily extended to other
biological targets for future drug repurposing applications. 
Financial Disclosure (Sharangdhar Phatak)
No
FDA Disclosure
Cleared:Yes
Keywords
Drug Repurposing
Polypharmacology
Chemical Genomics
Prostate / Breast Cancer / ACK1 Kinase
Abstract ID: 337
Effect Of ERÃŸ Agonists In Old WT Mouse Ventral Prostate
Author List
1. Presenting Author: Lena Herbst
2. Additional Author: Margaret Warner
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Diseases of the prostate, like BPH and cancer, occur frequently in men after the age of 50. Evidence indicates that estrogen
receptors (ERâ€™s) play a fundamental role during prostate development and epithelial differentiation with ERÃŸ as the
predominant receptor in the ventral lobe of the prostate. In addition, ERÃŸ has tumor suppressor properties, and therefore
may well be a target in the treatment of certain cancers. However, prostate cancer progression, from low to higher Gleason
grades, goes along with a loss in ERÃŸ expression. Hence, the strategy consists of sustaining and reactivating ERÃŸ
activity, and investigating the reason for the loss of ERÃŸ in cancer progression. In this study, we use two different
selective ERÃŸ agonists (KB101471 and LY3201) to examine their influence on prostatic growth and development.
Methods
C57BL/6 mice at the age of 13 months were treated with constant release pellets for 3 days as follows: (1) ten mice were
implanted with placebo pellets, (2) ten mice were implanted with KB101471 pellets (0.35 mg/ kg/ day), and ten mice were
implanted with LY3201 pellets (0.2 mg/ kg/ day) subcutaneously. Five mice per group were i.p. injected with testosterone
(5.7 mg/ kg) once at treatment day 1 and once at day 2. BrdU substrate (50 mg/ kg) was i.p. injected twice on treatment day
2 into all animals. Mice were sacrificed on day 3. The ventral prostate (VP) was dissected, embedded into paraffin and
further analyzed with histological stainings and immunohistochemistry.
Results
The histology showed an increased breakdown of the epithelial layer in LY3201 and KB101471 treated mice. Moreover,
testosterone treatment resulted in the infiltration of immune cells into the VP in the placebo treated group, and this
infiltration was attenuated by treatment with both ERÃŸ agonists. Preliminary immunohistochemical stainings
demonstrated a higher expression of ERÃŸ, a stronger expression of the tumor suppressor gene Dach1 and the autophagy
marker LC3-B in LY3201 and KB101471-treated mice.
Conclusion
Both investigated ERÃŸ agonists indicate promising effects on: (1) maintenance of ERÃŸ expression; (2) suppression of
inflammation; (3) antitumor activity; and (4) autophagic destruction of the epithelial layer. Underlying mechanisms have to
be further characterized.
Financial Disclosure (Lena Herbst)
No
FDA Disclosure
Cleared:Yes
Keywords
ER beta
ventral prostate
prostate cancer
immunohistochemistry
Abstract ID: 338
Social Media for Recruitment of Young Adult Testicular Cancer Survivors into Research Studies
Author List
1. Additional Author: Brittany Goodman
2. Additional Author: Sadie Conway
3. Presenting Author: Melissa Carpentier
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Testicular cancer is most commonly diagnosed among young adult men, an age group that is well-versed in social media
technologies. Social media sites are used by 72% of young adults, with Facebook representing their social network of
choice (73%); young adults are also the most active age demographic on Twitter, accounting for one-third of Twitter users
(Pew Research Center, 2010). Despite the salience of social networking in this age group, few studies have explored the
utility of social media for recruitment into research studies. Herein we describe the development and implementation of a
social media approach (i.e., Facebook, Twitter) for recruitment of young adult testicular cancer survivors into a study of
quality of life.
Methods
To prepare for our social media presence, we designed a study logo and acquired a toll-free number and study-specific
email address to facilitate questions and enrollment. We developed content for our Facebook profile describing our study
purpose, eligibility criteria, and contact information. For both Facebook and Twitter, we identified and â€œlikedâ€• or
â€œfollowedâ€• 200+ organizations and 90+ individuals (e.g., testicular cancer survivors and their loved ones) associated
with general health, cancer, or testicular cancer-specific causes. By targeting a broad audience, we sought to build
awareness about our study and encourage others to â€œlikeâ€• us, â€œshareâ€• our page, â€œfollowâ€• us, or
â€œretweetâ€• us. We also developed a working database of daily Facebook posts and Twitter tweets. These messages fell
into five categories: (1) study awareness; (2) active study recruitment; (3) study updates; (4) links to articles, resources, and
organizations of potential interest; and (5) links to our Facebook page or Twitter account.
Results
Our social media sites launched on July 30, 2012. In our first 10 days, we made nine Facebook posts (5 study awareness, 1
active recruitment, 1 link to resources, 2 links to Twitter); this resulted in one â€œshareâ€• and nine â€œlikesâ€•. We
tweeted nine times (6 study awareness, 1 link to resources, 2 links to Facebook); this led to one mention and two
â€œretweetsâ€•, along with the addition of 47 followers. In addition, we have received two email inquiries regarding study
participation.
Conclusion
Although preliminary, our results to date are promising with regard to the utility of social media in both increasing
awareness about and boosting recruitment into our research study. As time elapses, we will be able to determine whether
social media represents a viable method for reaching our target population.
Financial Disclosure (Melissa Carpentier)
No
FDA Disclosure
Cleared:Yes
Keywords
testicular cancer
survivors
recruitment
social media
Abstract ID: 339
Patient-Specific Respiratory Motion Compensation Via Surface Sensor Signals
Author List
1. Additional Author: Tian Cheng He
2. Additional Author: Kongkuo Lu
3. Additional Author: Po Su
4. Presenting Author: Zhong Xue
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
motion.jpg
Summary
Introduction
In image-guided percutaneous lung intervention, respiratory motion may cause larger targeting errors, longer procedure
time, and increased radiation to physicians and patients, especially for targeting small peripheral lesions in early lung
cancer diagnosis and treatment. Our previous work showed that the relationship between chest surface motion and lung
respiratory deformation can be established by a statistical model. In this work, we present a new algorithm to estimate the
CT images for patient-specific respiratory motion compensation via surface sensor signals using this model. Compared to
static CT image, the estimated CT images reflect patient's anatomy more accurately and may provide more efficient lung
tumor intervention guidance.
Methods
The algorithm consists of two stages: training stage and estimating stage. In the training stage, 4D CT data from a number
of subjects are used to estimate the relationship between chest surface motion (sensors tracked by using electromagnetic
devices) and 3D respiratory deformation. We first calculate the longitudinal respiratory deformations of each subject and
then transform these respiratory deformations onto a standard template space via registration. Then, a statistical model is
employed to establish the relationship between the chest surface movement and respiratory deformation in the template
space. In the estimating stage, given the intra-procedural 3D CT of the patient and the real-time tracked signals of chest
surface, we can estimate a series of CT images using the model. During the intervention, the best motion-compensated CT
is selected automatically by monitoring the EM-tracked skin sensors. To extract stable respiratory pattern of the patient, the
EM signals are analyzed for a period of time to enable sensor driven respiratory phase detection with relevant phase image.
During the procedure, the EM tracking system continuously detects skin sensor locations and compares them with the
different phase images to find the best match. As a result, the selected phase image can be used as a road-map to guide the
procedure.
Results
The motion estimation and respiratory phase selection algorithm had been tested using both phantom and three volunteer
data. After applying the trained statistical model from existing datasets, a series of 10 images were generated for each test
subject. The proposed method is able to analyze the EM signals derived from the chest surface, differentiate respiratory
phases, and select desired estimated image representing the current respiratory status. The results showed accurate
matching between the estimated image and the patient's real-time EM signals, and stable respiratory patterns of the subjects
were estimated.
Conclusion
We proposed a patient-specific respiratory motion compensation algorithm using chest surface signals. After estimating a
series of CT images using the chest surface signals recorded in a period of time, the best phase image can be automatically
picked for guiding the intervention. The experiment result showed the skin sensor driven motion compensation package
can be smoothly integrated into our existent EM-CT guidance system without significant change of clinical work-flow.
Financial Disclosure (Zhong Xue)
No
FDA Disclosure
Cleared:Yes
Keywords
Motion compensation
Respiratory motion
Medical image computing
Image-Guided Intervention
Abstract ID: 340
In Vivo Effect Of Chemotherapy And Exogenous G-CSF On CD114+ Neuroblastoma Stem Cell-like Subpopulation
Author List
1. Presenting Author: Paris Stowers
2. Additional Author: Danielle Hsu
3. Additional Author: Saurabh Agarwal
4. Additional Author: Denae Trahan
5. Additional Author: Anna Lakoma
6. Additional Author: Eveline Barbieri
7. Additional Author: Zaowen Chen
8. Additional Author: Eugene Kim
9. Additional Author: Jason Shohet
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
Neuroblastoma is a pediatric malignancy arising from neural crest of the sympathetic nervous system. Granulocyte
colony-stimulating factor (G-CSF) and chemotherapy are common components of treatment regimens for this aggressive,
neuroendocrine tumor. Previous work in our lab suggests the G-CSF receptor (CD114) may be a marker of a stem cell-like
subpopulation in neuroblastoma. These CD114+ cells possess qualities of self-renewal and increased tumorigenicity,
suggesting they may drive neuroblastoma formation and relapse. In this study, we investigated whether exogenous G-CSF
and chemotherapeutic agents affect this stem cell-like subpopulation using an orthotopic mouse model of neuroblastoma.
Methods
The renal capsules of nude mice were injected with 1 million luciferase-expressing neuroblastoma cells, and tumor
formation was confirmed in 22 of the 23 mice using IVIS imaging. Two weeks after the xenograft, 10 mice received
exogenous G-CSF (50 Âµg/kg; 5 injections per week for 3 weeks) or D5W. Five weeks after implantation, the tumors
were harvested and analyzed for CD114+ cell content and tumor size. 
This mice model was also used to evaluate the effect of chemotherapy. In this study, mice received chemotherapy (either
15 mg/kg Etoposide or 7.5 mg/kg Cytoxan) 3 days per week for 3 weeks. After the third cycle of chemotherapy, the
resulting tumors were harvested and CD114+ cells were quantified using flow cytometry.
Results
Flow cytometry analysis of the harvested tumor cells indicates exogenous G-CSF did not alter the proportion of
CD114+cells in the tumors. Additionally, G-CSF-exposed tumors were not significantly different than control tumors.
However, exposure to chemotherapeutic agents significantly enhanced the CD114+ subpopulation in the neuroblastoma
xenografts compared to untreated controls (p<0.05 for Cytoxan and p<0.05 for Etoposide).
Conclusion
Although, exogenous G-CSF did not affect tumor size or CD114+ cell content in this study, the effect may require a longer
period of G-CSF exposure. This experiment may be repeated with extended treatment duration. 
In vivo enrichment of CD114+ cells with both Etoposide and Cytoxan suggests this subpopulation may be relatively
resistant to chemotherapy compared to other tumor cells and may contribute to tumor relapse. Considering the high
tumorigenicity of CD114+ cells and this relative resistance, further studies should be done to characterize and target this
stem cell-like population in neuroblastoma.
Financial Disclosure (Paris Stowers)
No
FDA Disclosure
Cleared:Yes
Keywords
Neuroblastoma
Cancer Stem Cells
CD114
None
Abstract ID: 341
Building A Texas-based Leader In The Emerging Field Of Cellular Immunotherapy
Author List
1. Presenting Author: Gregg Sando
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Cancer immunology
Uploaded Files
none
Summary
Introduction
Cellular immunotherapeutics provide a new and powerful modality for the treatment of cancer and cancer-related
morbidity. Following recent advances in our scientific understanding of how the human immune system can be activated to
kill malignant cells, new technology and approaches are now being developed which involve directing powerful immune
responses against cancer. Initial clinical data indicate that cell-based immunotherapy may achieve significant responses in
patients with advanced disease and, equally important, these cell therapies are safe and well-tolerated by patients. Without
the side effects and long-term complications associated with chemotherapy and radiation, cell-based immunotherapy offers
the promise of inducing long-term cancer remission while maintaining a high quality of life for the patient during
treatment. 
Cell Medica Ltd. (London, UK) is developing cell therapies for the treatment of cancer associated with the oncogenic
Epstein Barr virus (EBV) and also for viral infections in patients following allogeneic hematopoietic stem cell (bone
marrow) transplant (allo-HSCT). The Companyâ€™s cancer cell therapy originated from the research at the Center for Cell
and Gene Therapy, a collaboration of Baylor College of Medicine, The Methodist Hospital and Texas Childrenâ€™s
Hospital. With equity investment from CPRIT and a group of top-tier investors including the Wellcome Trust, Invesco
Perpetual and Imperial Innovations, Cell Medica will build a leading-edge cell therapy company in Texas and launch a
clinical development program aimed at regulatory approval for Cytorex EBV to treat EBV associated lymphomas. As a
second clinical program, Cell Medica will also undertake a pivotal trial for Cytovir CMV to treat cytomegalovirus (CMV)
infections in patients following a bone marrow transplant. The CPRIT investment was made through a Commercialization
(Relocation) Award finalized in July 2012 which will lead to the creation of 20 development-related jobs in Texas to
manage the initial projects. Thereafter, assuming FDA approval for Cytorex EBV by 2016/2017, the Companyâ€™s
commitment to build its commercial manufacturing and national distribution operations in Texas should lead to very
significant job creation as cellular immunotherapy becomes more widely adopted in clinical practice.
Methods
 
Results
 
Conclusion
 
Financial Disclosure (Gregg Sando)
material? Yes
- Cell Medica
FDA Disclosure
Cleared:Yes
Keywords
Cell therapy
Lymphoma
CMV
T-cell
Abstract ID: 343
AXL: Novel Regulator Of p53 Via The MDM2-MDMX Complex
Author List
1. Presenting Author: Miriam Shadfan
2. Additional Author: Suthakar Ganapathy
3. Additional Author: Mei Yang
4. Additional Author: Hang Su
5. Additional Author: Zhi-Min Yuan
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
P53, known as â€œguardian of the genome,â€• is an essential transcription factor for effective tumor suppression and is
nearly universally inactivated in cancer cells either by direct mutations of p53 or deregulation of its function. Because p53
overexpression can actually lead to drastic cellular and pathological effects, a delicate balance of p53 is maintained via
negative regulation at the protein level by two essential proteins â€“ MDM2 and MDMX. We screened a library of tyrosine
kinases and identified AXL as a novel regulator of the MDM2-MDMX-p53 regulatory core. We hypothesized that AXL
stabilization of the MDM2-MDMX complex inhibits p53 activity, and therefore that inhibition of AXL could be utilized to
free up p53 activity and thereby sensitize tumor cells to irradiation-induced death.
Methods
The original screening for kinases that affect the MDM2-MDMX complex was luciferase-based. Western blots were used
to verify that AXL can stabilize the MDM2-MDMX complex, and thereby affect protein levels of p53. In these
experiments, we examined either exogenously expressed or endogenous proteins in various cell types including 293T,
A549, H1299, U-87 and U-251. Cell survival assays, senescence assays, and flow cytometry were used to validate changes
to p53 activity translated into cellular effects. AXL activity was inhibited both using depletion by siRNA and an inhibitor,
Foretinib. We used A549, U-251, and U-87 xenografts to validate our findings in vivo.
Results
We have demonstrated in vitro and in vivo that AXL suppresses p53 activity by stabilizing the
MDM2-MDMX complex, and inhibition of AXL can therefore activate p53, thereby sensitizing p53-wildtype cancer cells
to irradiation-induced death.
Conclusion
AXL has been established to play a role in cancer survival, invasiveness, and resistance to therapy. Inhibition of this kinase
has also been shown to sensitize cancer cells to drug-induced death. In this study, we show a new mechanism by which
AXL can promote cancer survival â€“ inhibition of the p53 pathway via MDM2 and MDMX. We demonstrate that
inhibition of AXL can induce p53 and subsequent cell death. In vivo, inhibition of AXL successfully
sensitized tumors to radiation treatment. Based on our results, we hypothesize that wildtype p53 can be used as a marker to
determine the ability of AXL inhibitors to sensitize cancer cells to radiation therapy.
Financial Disclosure (Miriam Shadfan)
No
FDA Disclosure
Cleared:Yes
Keywords
p53
mdm2
mdmx
axl
Abstract ID: 344
Increasing Colorectal Cancer Screening Rates Among Hispanic Men Through Patient Navigation
Author List
2. Additional Author: Mariluz Martinez
4. Additional Author: Raul Ramos
5. Additional Author: Jimmy Ramos
Oral Sessions
Poster Sessions
Status
Accepted
None
Yes
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
Introduction
Colorectal cancer (CRC) can be prevented if tissue changes are detected early and precancerous polyps are removed.
Patient level factors such as being low income, uninsured, and Hispanic are associated with low CRC screening rates. In
the US only 38.8% of Hispanic men compared to 58.4% of non-Hispanic white men age 50 or older have reported they
have ever had a colonoscopy, sigmoidoscopy or proctoscopy. In addition, many Hispanic men seek care only after
symptoms occur. While data indicates the incidence and death rate of CRC among Hispanic men has declined in the last
decade, Hispanics are more likely to be screened later and diagnosed with advanced stage CRC when compared to
non-Hispanic whites. The goal of University Health System (UHS) CRC Screening Male Navigation Program is to develop
a model to reduce cancer mortality by screening 300 men for colorectal cancer. The target population includes male, UHS
CareLink (county financial assistance program) members, age 50 and older who have had no prior CRC screening.
Methods
Our program aids in reducing the impact of CRC through the implementation of a multi-component, evidence-based
intervention using open-access endoscopy, bilingual patient navigation, one-on-one patient education, assisted
transportation to and from screening appointments, and colonoscopy services provided by a bilingual, Hispanic, colorectal
surgeon. This approach uses a combination of: 1) culturally appropriate, social cognitive theory based techniques to
educate patients, remove myths, and provide overall social support; and 2) system changes to remove organizational,
financial, and other major barriers associated with the completion of CRC screening colonoscopies.
Results
To date, the navigation team examined 472 medical records for eligibility, contacted 333 (70%) potential participants, and
successfully navigated 161 (48%) men through CRC screening. In total, 52 (32%) men had polyps removed of which 2
(1.2%) were confirmed cancerous.
Conclusion
Access to cancer screening, treatment, and education is a proven strategy to successful changes in reducing premature
deaths related to cancer. Use of a culturally competent patient navigation team and physician increases the likelihood that
Hispanic men will complete a CRC screening. The men who were successfully navigated have become role models in their
neighborhoods and their personal stories have been used to demonstrate how easily barriers can be over come to get this
much needed cancer screening.
No
FDA Disclosure
Cleared:Yes
Keywords
Colorectal
Screening
Navigation
Hispanic
Abstract ID: 345
Implementing Breast Biospecimens Best Practices In A Multi-Site Community Healthcare Network
Author List
1. Presenting Author: Diann Fine
2. Additional Author: Alastair Dunnett
3. Additional Author: Angela Cook
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
General Attendee
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The American Society of Clinical Oncology and the College of American Pathologists (CAP) have established guideline
recommendations for Immunohistochemical testing of estrogen and progesterone receptors and human epidermal growth
factor receptor 2 (HER2) testing in breast cancer. These guidelines reflect the principles expressed in National Cancer
Institute (NCI) Biospecimens Best Practices. Compliance with these guidelines promotes accuracy of the
immunohistochemical tests results used to help determine breast cancer treatment options.
Purpose/Objective: Implement national biospecimens best practices for breast cancer across a multi-site community
healthcare network and in multiple pathology practices.
Methods
The guidelines recommend certain measures to improve the standardization of pre-analytical variables. The criteria include
type of fixative, cold ischemia times and duration of tissue fixation. The fixative of choice is 10% neutral buffered
formalin. The guidelines recommend the cold ischemia time (time the tissue is handed from the surgical field to the time
the tissue is placed in formalin), be â‰¤1 hour. The recommended duration in fixative is 6-72 hours. Quarterly audits are
manually performed at five main hospitals with the cooperation of three independent pathology groups. All surgical cases
with breast specimens excluding cysts and abscesses are monitored. This exceeds CAP guidelines by including relevant
benign breast tissue. Cases are reviewed for documentation of fixation data. A 95-100% compliance rate is the expected
goal.This best practice initiative benefited from strong support from all three pathology practices. Multi-faceted
implementation efforts included education of pathologists and staff in all three practices at the five â€œcoreâ€• laboratories
and at the hospitals sending tissue to these histology lab locations; adaption of pathology practice forms to capture data in a
standard, easily accessible form; creation of a tracking tool; and regular audits and feedback to the practices, Seton Breast
Cancer Subcommittee and most recently to individual physicians.
Results
An analysis of data from the second quarter of 2011 through the second quarter of 2012 indicated overall improvement in
percentage compliance with the best practices guidelines and helped target areas for continued process improvement.
Conclusion
Implementing best practices guidelines within the hospital network and participating pathology groups has been a large
project with great success. The commitment to best practices raises the level of patient care and helps determine the best
course of treatment for those with cancer.
Financial Disclosure (Diann Fine)
No
FDA Disclosure
Cleared:Yes
Keywords
Biospecimen Best Practices
Breast
None
None
Abstract ID: 346
UHS Cervical Cancer Prevention Services â€“ A Su Salud Program
Author List
2. Additional Author: Karla Granado
3. Additional Author: Leah Trevino
Poster Sessions
Poster Sessions
Status
Accepted
None
N/A
General Information
Resident
N/A
Abstract History
Abstract Category
Uploaded Files
none
Summary
N/A
Introduction
The University Health System (UHS) Cervical Cancer Prevention Program offers primary and secondary cancer prevention
through culturally targeted, community-based education, free patient navigation, Pap tests and HPV vaccines. The program
utilizes mass media and community outreach to educate women and open-access scheduling, patient navigation and clinical
services to decrease well known barriers to cervical cancer screening in Bexar County residents. Currently 42% of women
in CareLink (county financial assistance program) receive Pap tests within three years. During the program 27,000
additional women will receive cervical screening services increasing the overall three-year screening rate to 80%.
Historically HPV vaccination initiation and completion rates for Bexar County women aged 18-26 years have been low at
17% and 3% respectively. By combining culturally effective education and navigation, we expect to increase these rates by
20%.
Methods
Outreach components of the program will employ several evidence-based strategies to encourage women to change their
health related behaviors. Health promotion and education messages will be distributed throughout Bexar County by
developing newsletters, patient reminders, public service announcements and hosting health fairs and community action
coalition meetings with volunteers. HPV vaccination messages are aimed at parents of 9â€“18 year olds, and unfunded
19-26 year olds. Pap test cervical cancer screening messages are aimed at women ages 18-64. Patient navigators will
support Carelink women through the screening and/or vaccination process and mitigate barriers to care. They w

Abstracts Data - Speaker Ready Room by One World

Transcription

Similar documents

Installation of Scrolling Ceiling

Installation of Scrolling Banner CNFS00 1

BETWEEN THE COVERS RARE BOOKS

Leaving Cert Craft Exam-Poster Question By Ruth Graydon

Dr. Roman Kezerashvili, Professor of Physics Leading the Poster

Pictorial Modernism Art Deco

Class Handout in PDF

71.02 - UK POS

poster packs - Oxford SA Blog

poster packs - Oxford SA Blog