bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1426: Racial variation in annexin A2(AnxA2) gene expression and poor outcome in triple-negative breast cancer
Authors: Gibbs Lee D. , Vishwanatha Jamboor K. 
Published: July 2016

Abstract
Background: Triple-negative breast cancer (TNBC) is identified by the absence of three major receptors that drive most breast cancers. The incidence of TNBC is also associated with health disparity due to its disproportionate occurrence in African American (AA) women. Our previous studies and others have shown that AnxA2 is overexpressed in TNBC, but its association with racial variation and outcomes is unknown.
Methods: AnxA2 gene expression was evaluated in breast cancer subtypes from The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) mRNA database that include 1,094 patients. Associations between clinical outcomes and AnxA2 gene expression were tested in a genome wide association study of combined publicly available datasets that include 4,147 patients.
Results: AnxA2 gene expression was significantly increased in TNBC in comparison to other breast cancer subtypes. Furthermore, AnxA2 gene expression was significantly elevated in AA women in comparison with Caucasian (CA) women and was associated with the disproportionate occurrence of TNBC in AA women. High expression levels of AnxA2 was associated with reduced overall survival (hazard of death = 2.66; 95% confidence interval {CI] = 1.14 - 6.25, P = 0.0192), reduced relapse free survival (hazard of relapse = 1.45; 95% confidence interval {CI] = 1.12 – 1.89, P = 0.0051), and reduced distant metastasis free survival (hazard of metastasis = 1.7; 95% confidence interval {CI] = 1.00 – 2.91, P = 0.048). AnxA2 gene expression was not associated with poor outcome in other intrinsic breast cancer subtypes, such as Luminal A, Luminal B, and Her-2, indicating the specific association of AnxA2 with the aggressive behavior of TNBC.
Conclusion: AnxA2 overexpression is associated with racial variation and is a potential prognostic candidate for TNBC.
Impact: AnxA2 has potential prognostic value, implicating a role for AnxA2 in the
aggressive biology of TNBC in AA women.
Citation Format: Lee D. Gibbs, Jamboor K. Vishwanatha. Racial variation in annexin A2(AnxA2) gene expression and poor outcome in triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1426.
Abstract 1435: Psychoimmunological effect of depression on cervical carcinoma: Genome-wide long noncoding RNA implications
Authors: Dai Wanjun , Yu Yinhua , Kang Yu 
Published: July 2016

Abstract
Objective: Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death among females in developing countries. Depression is a vital psychological factor for tumor progression. Long noncoding RNAs(LncRNAs) are a novel group of gene regulators and may contribute to the disease development. Herein, the study aims to discover the mechanisms of psychoimmunological effect of depression on cervical carcinoma from the perspective of long noncoding ribonucleic acid.
Methods: Six tumor tissues were obtained from Ib-IIa invasive squamous cell cervical carcinoma patients during laproscopic surgeries. They were divided into high-depressed group and low-depressed group according to the scoring system. LncRNA microarray experiments were performed. Expression levels of six lncRNA-mRNA pairs were confirmed by quantitative real-time PCR in other 20 patients’ materials.
Results: We found that 1621 lncRNA transcripts are differently expressed between high-depressed and paired low-depressed samples, with 510 up-regulated and 1111 down-regulated (fold-change&gt;2.0). Most of lncRNAs were found trans-regulated by three TFs with most credentiality: BCL11A,MEF2A and TBP. In the KEGG analysis, the most down-regulated mRNA involved was systemic lupus erythematosus (Maximun transcriptional domain coverage: 25.5%). In the LncRNA and mRNA Coexpression, the function of lncRNAs with most differently expressions was predicted in relationship with interleukin-1 receptor activity (Number of lncRNAs annotated: 15).
Conclusions: Our study identified that genome-wide LncRNA profiles are significantly altered in cervical carcinoma patients with worse depressed profiles, and the psychoimmunological effect of tumor progression needs further investigation.
Keywords: Depression, Cervical Cancer, Immunology, Long-noncoding RNA
Citation Format: Wanjun Dai, Yinhua Yu, Yu Kang. Psychoimmunological effect of depression on cervical carcinoma: Genome-wide long noncoding RNA implications. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1435.
Abstract 1456: Dexamethasone suppresses cytokine-induced dual oxidase 2 (Duox2) and VEGF-A expression in human pancreatic cancer cells in vitro and pancreatic cancer growth in xenografts
Authors: Wu Yongzhong , Antony Smitha , Meitzler Jennifer L. , Lu Jiamo , Juhasz Agnes , Jiang Guojian , Roy Krishnendu , Doroshow James H. 
Published: July 2016

Abstract
Chronic pancreatic inflammation is strongly associated with pancreatic cancer. We previously demonstrated that inflammatory cytokines interact to produce a Duox2 (one of 7 members of the NADPH Oxidase family)-dependent, reactive oxygen species (ROS)-related, pro-oxidant milieu that could increase the pathologic potential of pancreatic inflammation, enhancing malignant transformation. Furthermore, we have shown that Duox2 expression is upregulated in patients with chronic pancreatitis as well as pancreatic ductal adenocarcinoma (PDAC). Dexamethasone (Dex) has been reported to inhibit PDAC invasiveness, the formation of pancreatic intraepithelial neoplasia in genetically-engineered mouse models of pancreatic cancer, as well as epithelial to mesenchymal transition, and local tumor recurrence and metastasis in vivo. Using cultured human pancreatic cancer cell lines, we found that in a dose- and time-dependent fashion Dex inhibited cytokine (IFN-γ/LPS, IL-4, and IL-17)-mediated up-regulation of Duox2 and VEGF-A expression in several human pancreatic cancer cell lines, including BxPC-3, ASPC-1, and CFPAC-1. The effects of Dex were abolished by pre-treatment with the Dex antagonist RU-486. As expected, we did not observe anti-proliferative effects of Dex on PDAC cells in vitro. However, Dex strongly repressed Duox2 mRNA and protein expression as well as the growth of xenografts initiated from BxPC-3 cells; in contrast, for the MIA-Paca line that is unresponsive to cytokines in culture, Dex produced no effect on Duox2 expression and tumor growth when these cells were grown as xenografts. Examination of the human Duox2 promotor in silico revealed a putative negative glucocorticoid receptor (GR) binding element. Western analysis, using nuclear extracts from pancreatic cancer cells treated with Dex, revealed that both activated glucocorticoid receptor and certain co-repressors, such as NCOR-1/2 and histone deacetylases (HDAC1, 2, and 3) exist in human pancreatic cancer cell nuclei. Our ongoing experiments are focused on understanding the molecular mechanism of Dex-mediated Duox2 repression both in vitro and in vivo. In summary, these studies suggest that cytokine-related oxidant stress, generated by Duox2, could play a role in the progression of pancreatic cancer.
Citation Format: Yongzhong Wu, Smitha Antony, Jennifer L. Meitzler, Jiamo Lu, Agnes Juhasz, Guojian Jiang, Krishnendu Roy, James H. Doroshow. Dexamethasone suppresses cytokine-induced dual oxidase 2 (Duox2) and VEGF-A expression in human pancreatic cancer cells in vitro and pancreatic cancer growth in xenografts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1456.
Abstract 1483: MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin's lymphoma
Authors: Robinson Garrett L. , Rajagopalan Sangeetha , Brieschke Brigitte , Erdman Jennifer , Neill Jane , Flores-Lefranc Rodney E. , Foree Julia , Null William , Liu Jensing , Higgins Jack P. , Willert Erin K. 
Published: July 2016

Abstract
Molecular Templates has developed engineered toxin bodies (ETBs), potent recombinant immunotoxins that combine the specificity of an antibody fragment with the powerful direct cytotoxicity of the Shiga-like toxin A subunit to specifically destroy target expressing cells. The use of other immunotoxins and antibody-drug conjugates is limited to targets with tumor-specific cell surface expression that efficiently internalize. The ETB scaffold has been designed to overcome this limitation and promote forced internalization of ETBs, a property that expands the potential targets to receptors with poor internalization kinetics. An additional benefit to ETBs is the mechanism of action (MOA) which is unique to that of other oncology treatments.
CD20, a receptor that does not undergo rapid internalization, is a well characterized target for agents used to treat non-Hodgkin's lymphoma (NHL). Thus, successful CD20-targeted clinical strategies include monoclonal antibodies (mAbs) and radiolabeled mAbs that act on the cell surface. Molecular Templates’ lead compound, MT-3724, is a CD20-targeted ETB that has been engineered to force the rapid internalization of the immunotoxin after binding to CD20. MT-3724 has potent direct cell kill activity on CD20 positive lymphoma cells and is the first immunotoxin to CD20 to enter the clinic. The on-going phase I study being conducted at Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, and New York University Langone Medical Center has shown promising safety and efficacy in highly refractory NHL patients.
Once MT-3724 is delivered to appropriate cells, the Shiga toxin A subunit inhibits protein synthesis and promotes apoptosis of tumor cells. The difference in MOA allows for activity in the refractory setting, where resistance to other treatments has emerged, and may also allow for combination therapy. Pre-clinical studies with immunomodulatory drugs (IMiDs), PI3K and Bcl-2 inhibitors that are used in treatment of NHL have shown promising results when combined with MT-3724. MT-3724 is a promising novel agent in the treatment of NHL and other CD20 positive hematological malignancies. Data around the internalization kinetics, enzymatic activity, and combination with other agents will be presented.
Citation Format: Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jennifer Erdman, Jane Neill, Rodney E. Flores-Lefranc, Julia Foree, William Null, Jensing Liu, Jack P. Higgins, Erin K. Willert. MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin's lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1483.
Abstract 149: Integrated analysis of intratumor heterogeneity with genetic and epigenetic aberrations during colorectal cancer evolution
Authors: Kidogami Shinya , Niida Atsushi , Uchi Ryutaro , Takahashi Yusuke , Mori Masaki , Miyano Satoru , Mimori Koshi 
Published: July 2016

Abstract
[background] Intratumor heterogeneity (ITH) is presumably generated by branching clonal evolution of cancer cells. Recently, a multiregional sequencing approach, which sequences DNA sampled from geographically separated regions of a single tumor, has revealed branched evolution and ITH. In this study, we present genetic and epigenetic analysis of ITH in a series of nine colorectal cancers
[material and method] We conducted analysis of samples from geographically separated regions from nine colorectal tumors. From each of the nine tumor, we obtained 5-21 multiregional samples, which were 75 samples in total, together with 9 paired normal mucosa samples. For two cases, samples from liver metastases were obtained. We performed exome sequencing and copy number (CN), methylation, and mRNA expression array profiling.
[Result] Each of the multiregional mutation profiles harbored founder and progressor mutations; founder mutations are shared by all regions while progressor mutations are not. We found that mutations in well-known driver genes such as APC, KRAS, and FBWX7 were acquired as founder mutations, while mutations in PIK3CA recurrently occurred as progressor mutations, suggesting that PIK3CA mutations are a late event in the evolution of colorectal cancer. We counted each category of mutation and then identified a correlation between the number of founder mutations and the age of the patients. Our analysis showed that C &gt; T transitions at CpG sites are more prominent in founder mutations than in progressor mutations. Then, the multiregional CN profiles showed that amplifications of 7p, 13q, 10q, 20p, and 20q frequently occurred across all samples in multiple tumors, namely as founder CN alterations. Finally, our data showed that hypermethylations in CpG islands were more prominent in founder methylations than in progressor methylations, suggesting that CpG island hypermethylations mainly occur in the early phase of colorectal cancer evolution.
[Conclusion] In this study, our integrated analysis revealed not only extensive ITH, but also the evolutionary histories of the nine tumors. In particular, by focusing on founder and progressor mutations, we identified clues for decoding the life history of the tumors.
Citation Format: Shinya Kidogami, Atsushi Niida, Ryutaro Uchi, Yusuke Takahashi, Masaki Mori, Satoru Miyano, Koshi Mimori. Integrated analysis of intratumor heterogeneity with genetic and epigenetic aberrations during colorectal cancer evolution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 149.
Abstract 1502: Three intrinsic subtypes of prostate cancer with distinct pathway activation profiles differ in prognosis and treatment response
Authors: You Sungyong , Knudsen Beatrice , Erho Nicholas , Alshalalfa Mohammed , Takhar Mandeep , Ashab Hussam Al-deen , Davicioni Elai , Karnes Robert Jeffrey , Klein Eric A. , Den Robert B. , Ross Ashley E. , Schaeffer Edward M. , Garraway Isla P. , Kim Jayoung , Freeman Michael R. 
Published: July 2016

Abstract
In the era of precision medicine, genomic classifications of prostate cancer (PC) have not broadly impacted patient care. Here we present an integrative transcriptome analysis of 14 disease-related pathways in over 4,600 clinical specimens and 25 PC preclinical models. This approach provides a novel classification scheme, inclusive of 3 PC subtypes (PCS1-3), which predict disease progression and drug resistance. The PCS1 and PCS2 categories possess characteristics of luminal cells, while PCS3 exhibits basal features. Castration-resistant and metastatic cancers are over-represented in PCS1 and PCS3 tumors. All 3 subtypes are represented in commonly used PC cell lines; however, none of the mouse models we analyzed resembles PCS3. PCS classification using RNA expression data appears to be stable across primary and metastatic human tumors, cell lines, xenografts and mouse models. This new subtyping method provides novel opportunities for patient stratification that reflect specific features of tumor biology and may influence therapeutic decisions.
Citation Format: Sungyong You, Beatrice Knudsen, Nicholas Erho, Mohammed Alshalalfa, Mandeep Takhar, Hussam Al-deen Ashab, Elai Davicioni, Robert Jeffrey Karnes, Eric A. Klein, Robert B. Den, Ashley E. Ross, Edward M. Schaeffer, Isla P. Garraway, Jayoung Kim, Michael R. Freeman. Three intrinsic subtypes of prostate cancer with distinct pathway activation profiles differ in prognosis and treatment response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1502.
Abstract 1503: Discovery of new breast cancer relevant genes using the cancer genomics public database
Authors: Samant Ritika R. , Samant Rajeev S. 
Published: July 2016

Abstract
We used the cBio portal to query the importance of key players in breast cancer. Telomerase (TERT) is an important protein that ensures successful immortalization of cancer cells. Immortalization is a key step to establish uncontrolled cell division. MYC is an oncogene that is very relevant in breast cancer. Our searches showed that both genes (TERT and MYC) are amplified in a high percent of patients. We wanted to explore if there are genetic events that co-occur with telomerase amplification. We found that NONO gene mutation had a high tendency of co-occurrence with telomerase amplification. We wanted to understand if this subset of tumors with mutation of NONO reveals any additional correlations. Our query revealed that PDE4DIP (Phosphodiesterase 4D interacting protein) is amplified concurrent with the NONO mutation. There is no notable cancer related data on PDE4DIP in publicly available peer-reviewed publication records (PubMed). However, when we queried PDE4DIP, we discovered that it is amplified in a large majority of the breast cancer cases. Thus, it is surprisingly more common than TERT or MYC amplification. We propose that it is very important to understand the relevance of PDE4DIP and NONO to breast cancer.
Citation Format: Ritika R. Samant, Rajeev S. Samant. Discovery of new breast cancer relevant genes using the cancer genomics public database. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1503.
Abstract 1505: Radiogenomics defines key genomic network driving GBM invasion
Authors: Colen Rivka R. , Luedi Markus , Singh Sanjay K. , Hassan Islam , Gumin Joy , Sulman Erik P. , Lang Frederick F. , Zinn Pascal O. 
Published: July 2016

Abstract
PURPOSE
Clinical care and outcome in Glioblastoma (GBM) remains challenging due to the tumor's invasive grwoth. To establish personalized treatment options in GBM, discovery of genetic mechanisms essential for the tumor's invasion is needed. We have previously described radiogenomic approaches to diagnose gene networks non invasively by analyzing genomic data from TCGA. The purpose of the current reseach is to identify a genetic network that drives GBM invasion and can be targeted specifically.
METHOD AND MATERIALS
Using Kaplan-Meier statistics, the data of the two independent databases TCGA and REMBRANDT were used to validate the genetic netowork's impact on clinical outcome. The genes’ staus was assessed in a panel of human glioma stem cells (GSCs) and conventional proneural, classical and mesenchymal GBM cell lines using RT-PCR. Differentiation potential (Tuj1+ve, S100A+ve, and GFAP+ve), self-renewal (limiting dilution assays), invasion (Boyden chamber) and proliferation (BrdU) were assessed. Gain (lentiviral vectors) and loss (SMARTchoice Inducible shRNA) of function experiments were performed. Orthotopic xenograft models (nude mice) were used to characterize the genes impact in vivo. Potential FDA approved therapeutics were identified using connectivity map.
RESULTS
Texture analysis based on radiogenomics significantly predicted the genes responsible for invasion of GBM in a non-invasive manner. Invasion in both, in vitro and in vivo was significantly decreased upun downregulation of this gene network. Transcriptome micro-array analysis showed that an upregulation of the described genes results in class switching from proneural to mesenchymal sub-types. Cmap derived therapeutics could significantly inhibit the gene network's activitiy and hence invasion.
CONCLUSION
The describend genes could be essential drivers of molecular subtypes and invasion in GBM. The therapeutics defined with cmap offer a targetted therapy to adress these key features of GBM pathogenesis. Noninvasive radiogenomics-based identification of tumor subgroups and potential treatment approaches can significantly contribute to personalized therapy.
CLINICAL RELEVANCE/APPLICATION
The described gene network seems to be key for GBM pathogenesis. Noninvasive, radiogenomics-based subgroup identification and specific novel treatment approaches can significanty contribution to personalized GBM therapy.
Citation Format: Rivka R. Colen, Markus Luedi, Sanjay K. Singh, Islam Hassan, Joy Gumin, Erik P. Sulman, Frederick F. Lang, Pascal O. Zinn. Radiogenomics defines key genomic network driving GBM invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1505.
Abstract 1510: Subtype-specific cancer driver gene detection improves sensitivity to detect drivers
Authors: Fu Yao , Chhibber Aparna , Bani-Asadi Narges , Lam. Hugo YK 
Published: July 2016

Abstract
Identifying cancer driver mutations is a crucial step toward understanding the underlying mechanisms of oncogenesis. However, driver gene detection is complicated, considering the inherent complexity and heterogeneity of cancer.The past decade has seen the large-scale application of next-generation sequencing technologies (NGS) in cancer genomics, and many methods have been published utilizing NGS to detect novel oncogenic drivers. However, the low concordance across methods raises the concern about false positives and negatives in those findings. In particular, proper modeling of the background mutation profile (known to be affected by multiple factors) is critical to improving precision and recall in driver detection. Though intra-sample heterogeneity in the background mutation profile is considered to some extent in multiple methods, most computational driver detection methods assume a homogeneous mutational landscape across cancer samples. With more and more subtypes being discovered in various cancers, the assumption is largely untenable.
In this study, we present a driver gene detection framework taking into account the heterogeneous mutational context in a cancer cohort. Our approach improves sensitivity to detect drivers by first pre-selecting a more uniform sample subset to apply driver detection algorithms. We combine this method with enhancements to an existing ensemble approach that combines methods with different assumptions about the characteristics of driver mutations (recurrence across samples, functional impact bias and positional clustering). We apply this combined approach to ∼750 breast invasive carcinoma samples from The Cancer Genome Atlas. In this dataset, genes identified by our approach show higher enrichment in known cancer driver genes compared to other methods, and the subtype-driven method identifies additional potential drivers that are missing in overall analysis.
Citation Format: Yao Fu, Aparna Chhibber, Narges Bani-Asadi, Hugo YK Lam. Subtype-specific cancer driver gene detection improves sensitivity to detect drivers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1510.