bluuebunny/crossref_metadata_2025_split huggingface dataset:
Playing the Wrong Game
Authors: Meir Reshef , Parkes David 
Published: November 2015

In many situations a player may act so as to maximize a perceived utility that is not exactly her utility function, but rather some other, biased, utility. Examples of such biased utility functions are common in behavioral economics, and include risk attitudes, altruism, present-bias and so on. When analyzing a game, one may ask how inefficiency, measured by the Price of Anarchy (PoA) is a?ected by the perceived utilities.
The smoothness method [16, 15] naturally extends to games with such perceived utilities or costs, regardless of the game or the behavioral bias. We show that such biasedsmoothness is broadly applicable in the context of nonatomic congestion games. First, we show that on series-parallel networks we can use smoothness to yield PoA bounds even for diverse populations with di?erent biases. Second, we identify various classes of cost functions and biases that are smooth, thereby substantially improving some recent results from the literature.
Abstract A1-10: The iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin
Authors: Freeman Adam N. , Martin T John , Henderson Michael A. , Makalic Enes , Kapuscinski Miroslaw K. , Schmidt Daniel F. , Hopper John 
Published: November 2015

Abstract
Parathyroid hormone-related protein (PTHrP), the product of the PTHLH gene, has long been implicated in breast cancer. Its expression is thought to favor and, potentially, facilitate metastasis to bone. Paradoxically, a prospective clinical study clinical suggests that its production in primary breast cancers is actually protective, affording a better prognosis than its absence. Multiple recent Genome-Wide Association Studies (GWAS) have confirmed a single susceptibility locus immediately upstream of the PTHLH gene to be associated with breast cancer. This was again reproduced in the recent iCOGS GWAS, which involved over 90,000 European subjects. In spite of a single SNP, rs10771399, being uniquely reported and reproduced by prior studies, we demonstrate 4 discrete overlapping signals by utilizing forward selection logistic regression and LASSO techniques. Two of these signals are centered and superimposed around rs10771399, ~40kbp upstream of PTHLH, a third lies a further 100kbp upstream, and the fourth lies a further 250kbp upstream over the next gene, CCDC91. While the causation of this signal remains elusive, multiple putatively contributory variations are captured by these signals.
Citation Format: Adam N. Freeman, T John Martin, Michael A. Henderson, Enes Makalic, Miroslaw K. Kapuscinski, Daniel F. Schmidt, John Hopper. The iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-10.
Abstract A1-21: NOTCH 1 and NOTCH 3 expressions for early stage of non-small cell lung cancer
Authors: Cho Eun Kyung , Ha Seung Yeon , Lee Jae Ik , Hong Junsick , Sim Sun Jin , Park Jinny , Shin Dong Bok , Lee Jae Hoon 
Published: November 2015

Abstract
Backgrounds: Notch gene Encode 300kDa single-pass transmembrane receptors. It can variously serve as an oncogene or a tumor suppressor and a repressor or inducer of terminal differentiation. It also regulate cell division, differentiation and survival of stem and/or progenital cells in wide range tissues. We examined Notch 1 and 3 to study the correlation of Notch expression and prognosis for non-small cell lung cancer.
Methods: Paraffin-embedded tissue microarrays were constructed. We analyzed Notch 1 and 3 by immunohistochemical stain on surgical tumor specimens.
Results: One hundred fifty-nine of 185 resected tissues for lung cancer (median age 62 years) were available for immunohistochemical stain. The types of tumor histology were adenocarcinoma;54, squamous cell carcinoma:79, others;26. 121 patients were taken lobectomy and 38 were done pneumonectomy. Notch 1 and 3 receptors were detected in 119 (74.8%) and 130 (81.7%) of total 159 (M:F=114:45) tumor tissues, respectively. Notch 1 receptors showed higher expressions on squamous cell carcinoma than non-squamous cell carcinoma (58.8% vs. 37.8%, p=0.03). However, it was not correlated with sex, smoking status or advanced stages. Five year-relapse free survival (RFS) and overall survival (OS) were 57.4 % and 59.3 % in 159 patients, respectively. Patients with any expression of Notch1 or 3 have correlated with neither RFS nor OS. 5 year OS for patients who showed Notch 3 expression were 62 % and the others were 47.8%, however, it was not statistically significant (p= 0.165). Both of their expressions were detected in 106 of 159 (66.7%) tumor tissues. Sixteen (10 %) had negative expressions in both of them. The patients with both positive expressions had the tendency of longer OS than all negative patients. Their 5 year OS were 60.8 % vs. 38.2% (p=0.068) and 5 year RFS were 56.5% vs. 49.7 % (p=0.35).
Conclusions: Notch 1 showed higher expression on squamous cell carcinoma. Neither Notch 1 nor 3 have correlated with RFS or OS, but patients with both expressions had the tendency of longer overall survival.
Citation Format: Eun Kyung Cho, Seung Yeon Ha, Jae Ik Lee, Junsick Hong, Sun Jin Sim, Jinny Park, Dong Bok Shin, Jae Hoon Lee. NOTCH 1 and NOTCH 3 expressions for early stage of non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-21.
Abstract A1-43: Targeted amplicon-based next-generation sequencing of routine solid tumor specimens to detect clinically relevant somatic alterations
Authors: Hovelson Daniel H. , McDaniel Andrew S. , Johnson Bryan , Cani Andi K. , Rhodes Kate , Williams Paul D. , Liu Chia-Jen , Bandla Santhoshi , Grasso Catherine S. , Quist Michael J. , Sadis Seth , Rhodes Daniel R. , Tomlins Scott A. 
Published: November 2015

Abstract
Background: Although precision medicine approaches have revolutionized oncology, widespread adoption requires robust, inexpensive approaches enabling the targeted assessment of all relevant alteration classes from routine tissue samples.
Methods: Here we interrogated &gt;7,000 cancer exomes and transcriptomes, along with &gt;30,000 array based cancer genomes to identify recurrent somatic alterations (mutations, copy number alterations [CNAs] and gene fusions) across solid tumors. From this analysis, we developed and validated an integrated multiplexed PCR based Ion Torrent next generation sequencing panel (Oncomine Cancer Research Panel [OCP]) targeting the actionable somatic cancer genome optimized for 20ng of formalin-fixed, paraffin-embedded (FFPE) tissue isolated DNA/RNA.
Results: We validated the OCP using FFPE cell line mixtures, as well as a prospective cohort of 104 FFPE tumor specimens sent for concurrent clinical molecular testing, with &gt;97% sensitivity and specificity for the presence/absence of KRAS, EGFR, BRAF and ALK point mutations, indels or gene fusions in this molecular testing cohort. We also applied the OCP to 100 lung cancers, identifying known and novel alterations, including ALK and ROS1 gene fusions. Lastly, applying the OCP to 116 prostate cancers, including 50 previously treated samples, we recapitulated known molecular subtypes, observed distinct profiles according to previous treatment and obtained 100% concordance for isoform specific TMPRSS2:ERG gene fusion detection compared to qPCR. Additionally, OCP profiling supports a novel molecular subtype of prostate cancer defined by IDH1 R132 hotspot mutations and informed on resistance mechanisms in a pre- and post-treatment sample pair. Importantly, 44%, 35% and 9% of patients in the molecular testing, lung and prostate cancer cohorts, respectively, harbored additional alterations (beyond routine molecular testing) associated with FDA approved or NCCN guideline referenced therapies.
Conclusions: Through analysis of both DNA and RNA to assess the actionable somatic cancer genome, the validated OCP panel may have utility in both clinical and research settings.
Citation Format: Daniel H. Hovelson, Andrew S. McDaniel, Bryan Johnson, Andi K. Cani, Kate Rhodes, Paul D. Williams, Chia-Jen Liu, Santhoshi Bandla, Catherine S. Grasso, Michael J. Quist, Seth Sadis, Daniel R. Rhodes, Scott A. Tomlins. Targeted amplicon-based next-generation sequencing of routine solid tumor specimens to detect clinically relevant somatic alterations. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-43.
Abstract A1-61: ANT2 shRNA downregulates multiple onco-miRNAs through the targets, TIMP-2, and suppresses cell death in human hepatocellular carcinoma cells
Authors: Baik Seung Hyun , Lee Jong Kuen , Kim Chul-Woo 
Published: November 2015

Abstract
Micro RNA (miRNAs) are negative regulators of gene expression functioning either as tumor suppressors or oncogenes in cancer. As expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood we investigated the roles of specific miRNAs in this study. We examined that knockdown of ANT2 by shRNA down-regulates onco-miRNA (miR-19a and miR-96) expression levels, and leads to the suppression of proliferation and tumorigenesis in HCC cell line. Microarray profiling of miRNAs showed that the expression of miR-19a and miR-96 were markedly upregulated in both Hep3B and HepG2 cells and their ectopic expression dramatically induced the proliferation and the ability of hepatoma cells to form colonies in vitro, while the inhibition of miR-19a and miR-96 reduced this effect. To investigate the in vivo function, we implanted miR-96 overexpressed-HepG2 in Balbc/nude mice and demonstrated that increase of miR-96 induces tumor growth. We also found that miR-19a and miR-96 are downregulated by ANT2 shRNA, which in turn induces the accumulation of TIMP-2 and the inactivation of p300. Taken together, our results suggest that miR-19a and miR-96 may play an important role in promoting proliferation of human HCC cells and also suggest that the knock down of ANT2 by shRNA directly down-regulates multi-onco-miRNAs, ultimately resulting in suppression of tumor growth
Citation Format: Seung Hyun Baik, Jong Kuen Lee, Chul-Woo Kim. ANT2 shRNA downregulates multiple onco-miRNAs through the targets, TIMP-2, and suppresses cell death in human hepatocellular carcinoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-61.
Abstract A2-02: SF3B1 mutations constitute a novel therapeutic target in breast cancer
Authors: Maguire Sarah , Leonidou Andri , Wai Patty , Marchio Caterina , Ng Charlotte , Sapino Ana , Vincent-Salomon Anne , Reis-Filho Jorge , Weigelt Britta , Natrajan Rachael 
Published: November 2015

Abstract
Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, pancreatic cancer and at lower frequencies in breast cancer. To investigate whether dysfunction in RNA splicing is implicated in the pathogenesis of breast cancer, we performed a re-analysis of published exome and whole genome sequencing data. This analysis revealed that mutations in spliceosomal component genes occurred in 5.6% of unselected breast cancers, including hotspot mutations in the SF3B1 gene, which were found in 1.8% of unselected breast cancers. SF3B1 mutations were significantly associated with ER-positive disease, AKT1 mutations and distinct copy number alterations. Additional profiling of hotspot mutations in a panel of special histological subtypes of breast cancer showed that 16% and 6% of papillary and mucinous carcinomas of the breast harboured the SF3B1 K700E mutation. RNA sequencing identified differentially spliced events expressed in tumours with SF3B1 mutations including the protein coding genes TMEM14C, RPL31, DYNL111, UQCC and ABCC5 and the long non-coding RNA CRNDE. Moreover, SF3B1 mutant cell lines were found to be sensitive to the SF3b complex inhibitor spliceostatin A and treatment resulted in perturbation of the splicing signature. Our findings indicate that albeit rare, SF3B1 mutations result in alternative splicing events, and may constitute drivers and a novel therapeutic target in a subset of breast cancers.
Citation Format: Sarah Maguire, Andri Leonidou, Patty Wai, Caterina Marchio, Charlotte Ng, Ana Sapino, Anne Vincent-Salomon, Jorge Reis-Filho, Britta Weigelt, Rachael Natrajan. SF3B1 mutations constitute a novel therapeutic target in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-02.
Abstract A2-08: Lymph node metastasis-related genes discovered through patient-derived xenograft models
Authors: Moon Hyeong-Gon , Moon Hyun Hye , Han Wonshik , Noh Dong-Young 
Published: November 2015

Abstract
Background PDX model (Patient-derived xenograft model), one of the several advanced techniques for researching cancer, have appeared to overcome and supplement limitation of cell line based cancer research techniques.
Purpose/ Methods To observe variation of gene level during organ-specific metastasis in breast cancer patients, we made PDX model after transplanting primary tissues from TNBC breast cancer patients to NOG-SCID mouse. Then we performed RNA sequencing and analyzed mRNA expression dataset using both metastatic tissues of axillary lymph node and tissues from xenograft tumor which was grown in mouse fat fad. Using breast cancer cell lines, selected genes from RNA sequencing and mRNA array dataset were examined their expression level by RT-PCR and qRT-PCR techniques. In addition, migration ability was also confirmed by migration assay in each cell line.
Results TMSB4X, ANXA2P2, RPLP1 and IGFBP2 were more expressed in LN metastatic tissues than primary tissues and MGP, PROM1, MIA, KRT17 and KRT15 were downregulated in LN metastatic tissues. As a result of RT-PCR, qRT-PCR and migration assay, we knew that TMSB4X, ANXA2P2 and RPLP1 were mostly expressed in 14 breast cancer cell lines except some cell lines, and MIA was highly expressed in TNBC cell lines except MDA-MB-453. In addition, Hs578T, MDA-MB-231, HCC70, HCC38 and BT20 cell line had much higher migration ability than other cell lines.
Discussion PDX model, generated by tissues from breast cancer patients, represents similar changes of gene expression or mutation as compared with the patients. In addition, PDX model can preserve gene expression patterns and mutation profiles. Therefore, candidate gene screening for lymph node metastasis in PDX model is a meaningful process for applying clinical study. Tumor metastasis ability is usually determined by migration or invasion ability of cancer cells, and specific signaling pathways that related to migration or invasion are also important to tumor metastasis mechanisms.
Citation Format: Hyeong-Gon Moon, Hyun Hye Moon, Wonshik Han, Dong-Young Noh. Lymph node metastasis-related genes discovered through patient-derived xenograft models. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-08.
Abstract A2-12: Opposing roles of the 19S regulatory and 20S core proteasomal subunits in controlling sensitivity to proteasome inhibitors
Authors: Cho Min Y. , Acosta-Alvear Diego , Kampmann Martin , Wild Thomas , Choudhary Chuna Ram , Weissman Jonathan S. , Walter Peter 
Published: November 2015

Abstract
Targeted therapies for cancer are often hindered by the variable genetic makeup within and between tumors. This hurdle makes the identification of therapeutic targets challenging. Genetic susceptibilities found within networks encoded in the genome of a cancer cell can provide such therapeutic opportunities. Essential cellular networks overseeing homeostasis are often rewired in tumors, providing a landscape where synthetic lethal pairs may exist. A prominent example is the susceptibility of multiple myeloma (MM) cells to proteasome inhibitors. Because of their highly secretory nature, the proteasomes of MM cells can be burdened in a load-versus-capacity tug-of-war. This renders MM cells sensitive to proteasome inhibitors. Unfortunately, single agent therapies against the proteasome do not provide a cure, as tumor cells often acquire resistance. Because of this, we sought to understand how MM cancer cells respond and adapt to proteasome inhibition. Utilizing ultra-complex shRNA libraries, we screened several MM cell lines exposed to the proteasome inhibitor bortezomib. In these screens, we identified several genes that either sensitize or protect MM cells towards bortezomib intoxication. Unexpectedly we found that, contrary to knockdown of genes encoding subunits of the 20S core particle of the proteasome, knockdown of genes encoding subunits of the 19S regulatory particle of the proteasome lead to bortezomib desensitization. To understand the nature of this phenotype, we queried proteome changes in bortezomib treated cells where we ablated a single 19S subunit. By performing ubiquitin-remnant profiling and total proteome SILAC experiments, we identified several proteins involved in autophagy and NF-κB signaling as potential mediators of the protective phenotype. We are currently investigating the roles of components of these pathways in tailoring the response towards bortezomib. We surmise that some of these will be amenable for pharmacological targeting in developing novel combination therapies.
Citation Format: Min Y. Cho, Diego Acosta-Alvear, Martin Kampmann, Thomas Wild, Chuna Ram Choudhary, Jonathan S. Weissman, Peter Walter. Opposing roles of the 19S regulatory and 20S core proteasomal subunits in controlling sensitivity to proteasome inhibitors. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-12.
Abstract A2-21: Cancer malignancy induced by C-terminal truncated HBx in Huh-7 Hepatocellular carcinoma cells
Authors: Gal Myeong-Eun Je , Yi Eui-Yeun , Jung Seung-Youn , Kim Yung-Jin 
Published: November 2015

Abstract
Hepatitis B virus-encoded HBx is well known causative factor for the Hepatocellular carcinoma (HCC). HBx interferes with several signaling pathways that are associated with cell proliferation and apoptosis. HBx c-terminal region has been known to play important roles in HBV associated HCC. HBx C-terminal mutant was known to show increased proliferation and invasiveness. In this study, we investigated a molecular mechanism of cancer malignancy induced by C-terminal truncated HBx. Huh-7 Hepatocellular carcinoma cells stably transfected with C-terminal truncated HBx showed higher migrative and invasive phenotype. In addition, the cells were more resistant to doxorubicin compared to cells transfected with full-length HBx. We also observed a higher efflux activity in the cells transfected with C-terminal truncated HBx due to the increased expression of ABCB1. These results suggest that C-terminal truncated HBx up-regulate ABCB1 expression which results in the enhanced efflux of drug. Therefore cancer cells containing C-terminal truncated HBx acquire drug resistancy, and show more malignant phenotypes.
Citation Format: Myeong-Eun Je Gal, Eui-Yeun Yi, Seung-Youn Jung, Yung-Jin Kim. Cancer malignancy induced by C-terminal truncated HBx in Huh-7 Hepatocellular carcinoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-21.
Abstract A2-32: Identification of withaferin A as a novel cancer stem cell inhibitor to overcome drug resistance in non-small cell lung carcinoma
Authors: Cheng Tai-shan , Tsai Yu-Chen , Wu Alexander T. H. , Chang Peter M. H. , Hsu Wei-Hsiang , Lai Jin-Mei , Huang Chi-Ying 
Published: November 2015

Abstract
Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance. In this study, we focus on screening drugs that target CSCs to improve the current treatment outcome and overcome drug resistance in patients with lung cancer. We used publicly available embryonic stem cell and CSC-associated gene signatures to query the Connectivity Map (CMap) for potential drugs that can, at least in part, reverse the gene expression profile of CSCs. High scores were noted for several phenothiazine-like antipsychotic drugs, including trifluoperazine and perphenazine. The combination of gemcitabine with either trifluoperazine or perphenazine shows synergistic effects in anti-NSCLC cells. By using L1000 and CMap analysis, we identified withaferin A (WA) as a potential drug, which shares similar gene expression patterns to trifluoperazine or perphenazine combine with gemcitabine and to reverse differential gene expression of stem-like cell vs. differential cell. Further experiments demonstrated that WA significantly suppressed cancer stemness associated phenotypes, shown by decreasing side population and tumor spheroid formation. Furthermore, WA was accompanied by down-regulation of JAK2/STAT3 signaling pathway. The combination of WA and cisplatin significantly reduced the number of cancer spheroids and attenuated the proportion of ALDH+ cell population in CL97 lung spheroids, which was resistant to cisplatin treatment alone. In vivo study also demonstrated the anti-tumor effect of WA treatment. In conclusion, WA was identified as a potential anti-cancer stem cell inhibitor, which could also inhibit tumorigenesis and overcome cisplatin resistance in lung cancer.
Citation Format: Tai-shan Cheng, Yu-Chen Tsai, Alexander T. H. Wu, Peter M. H. Chang, Wei-Hsiang Hsu, Jin-Mei Lai, Chi-Ying Huang. Identification of withaferin A as a novel cancer stem cell inhibitor to overcome drug resistance in non-small cell lung carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-32.