bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2162: Gene expression profile for predicting survival in ovarian cancer across two independent datasets
Authors: Yoshihara Kosuke , Tajima Atsushi , Yahata Tetsuro , Kodama Shoji , Fujiwara Hiroyuki , Suzuki Mitsuaki , Onishi Yoshitaka , Hatae Masayuki , Sueyoshi Kazunobu , Fujiwara Hisaya , Kudo Yoshiki , Kotera Kohei , Masuzaki Hideaki , Tashiro Hironori , Katabuchi Hidetaka , Inoue Ituro , Tanaka Kenichi 
Published: February 2011

Abstract
Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. To identify a progression-free survival (PFS) related profile for predicting survival, advanced-stage serous ovarian cancer tissues from 110 patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We first selected 88 PFS-related genes by a univariate Cox model (p &lt; 0.01). To avoid overfitting our dataset, we then adjusted regression coefficients of the genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index for each patient based on the 88-gene expression profile with the estimated coefficients was significantly correlated with PFS time as a continuous variable. In multivariate analysis, the prognostic index was independently associated with PFS time compared to other clinical factors [hazard ratio (HR), 4.84; 95% confidence interval (CI), 3.50-6.55; p &lt; 0.001]. This prognostic ability was validated using an external validation dataset (n = 87) and proven by multivariate analysis (HR, 1.25; 95% CI, 1.08-1.45; p = 0.0032). The correlation between the prognostic index and overall survival time was confirmed in the two independent datasets. Furthermore, biological characterization of 88 PFS-related genes mainly highlighted several oncogenic signaling pathways. This PFS-related profile is the first step toward clinical practice for optimizing clinical management for advanced-stage serous ovarian cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2162.
Abstract 2166: Identification of novel epigenetically silenced genes by a global reactivation screen of prostate cancer
Authors: Ibragimova Ilsiya , de Cáceres Inmaculada Ibáñez , Hoffman Amanda M. , Al-Saleem Tahseen , Hudes Gary R. , Ochs Michael F. , Cairns Paul 
Published: February 2011

Abstract
The epigenetic alteration of aberrant DNA methylation of CpG island in the promoter region is a common mechanism of inactivation of tumor suppressor genes in cancer cells and a number of other cancer genes have been identified as hypermethylated with associated loss of expression in prostate cancer. By definition, a candidate gene approach has resulted in the examination of only a limited number of genes for epigenetic alteration. Many other tumor suppressor and cancer genes important in prostate tumorigenesis likely remain to be identified. A global approach to the identification of epigenetically silenced genes in prostate tumor cells could provide methylation signatures for early detection and for prognostic and predictive classification studies, identify novel targets for therapy, and lead to further elucidation of the biology of this disease.
One global approach to the identification of epigenetically silenced genes in tumor cells is based on the reversal of epigenetic silencing by drugs such as 5-aza-2 deoxycytidine resulting in re-expression analyzed by well-annotated gene expression arrays. This approach can preferentially identify re-expression of epigenetically silenced genes over methylated CpG islands that do not affect transcription. A proportion of the reexpressed genes will have been silenced by promoter hypermethylation in the untreated tumor cell lines.
In this study we performed a demethylating drug-based global epigenetic reactivation screen with an expression microarray on 4 well-established prostate cancer cell lines (LNCaP, DU-145, PC-3 and MDA2b) to identify new methylated genes in prostate cancer. A total of 2998 genes were found to have at least 2-fold upregulation of expression after drug treatment in one or more of four prostate tumor cell lines. Using qMSP and bisulfite sequencing, we studied the first 45 upregulated genes that were prioritized by examination of expression status in the normal cell counterpart compared to the tumor cell and the presence and location of a CpG island in the promoter region. Validation studies revealed several novel genes hypermethylated in primary prostate tumors compared to normal prostate that may have utility in methylation-based detection of prostate cancer tests.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2166.
Abstract 2178: Serial analysis of gene expression (SAGE) of esophageal squamous cell carcinoma: ADAMTS-16 is up-regulated in esophageal squamous carcinoma
Authors: Sakamoto Naoya , Oue Naohide , Noguchi Tsuyoshi , Sentani Kazuhiro , Anami Katsuhiro , Sanada Yuichi , Yoshida Kazuhiro , Yasui Wataru 
Published: February 2011

Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. To identify potential targets for diagnosis and therapeutics of ESCC, we performed Serial Analysis of Gene Expression (SAGE) on the ESCC sample. We generated the SAGE library from one ESCC sample and obtained a total of 14,430 tags, including 5,765 that were unique. By comparing SAGE tags from ESCC samples with those from normal human squamous esophagus (Gene Expression Omnibus accession number, GSM52501), we found several genes and tags that were differentially expressed between ESCC and normal squamous esophagus. Among these, we focused on the ADAM metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16) gene. ADAMTS has been described as part of a family of zinc dependent proteases (metzincin family), which play important roles in a variety of normal and pathological conditions including arthritis and cancer. Although ADAMTS16 is expressed in some organs, the relationship with cancers, including ESCC, has not been studied. Quantitative reverse transcription-polymerase chain reaction analysis showed a high level of ADAMTS16 expression in 8 out of 20 ESCC samples (40%) but not in 15 kinds of normal tissues. We also investigated the mRNA expression levels of SCCA1, which encodes SCC antigen. High levels of SCCA1 mRNA expression were found in 4 of 20 cases (20%). We then investigated the relation of ADAMTS16 expression to clinicopathologic characters and found that ADAMTS16 overexpression correlated with the advanced T grade (p = 0.0215). Western blot analysis revealed that ADAMTS16 protein expression was detected in all 4 ESCC cases, whereas in 1 of the 4 corresponding non-neoplastic mucosa. Furthermore, ADAMTS16 protein was detected in culture media from the TE5 ESCC cell line which expressed significant level of ADAMTS16 mRNA, indicated that ADAMTS16 is surely secreted. To evaluate the biological significance of ADAMTS16 in ESCC, we performed MTT assay and transwell invasion assay. These examination revealed that knockdown of ADAMTS16 by siRNA in TE5 cells inhibited both cell growth and invasion ability. These results suggest that ADAMTS16 has a high potential as a serum tumor marker and therapeutic target for ESCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2178.
Abstract 2179: Computational pharmacogenomics analysis of human cancer cell lines
Authors: Edelman Elena 
Published: February 2011

Abstract
Purpose:
The goal of this study is to use cell-based drug screening and genome-wide molecular information to identify fundamental genomic alterations useful for clinical applications.
Experimental Approach:
Molecular data has been collected in the form of high-throughput microarray-based assays measuring gene expression and copy number changes for 294 cell lines, as well as cell-based drug sensitivity measures for 110 drugs. A computational analysis approach is taken to integrate information from the large cancer cell line datasets to discover predictive biomarkers that can be used to better guide targeted cancer drugs. Cancer genes and gene networks that are vital in a cancer cell's sensitivity or resistance to these drugs are identified by first locating genomic regions of recurrent amplification and deletion across the entire cell line panel. These regions are further analyzed for copy number associations with marked drug sensitivity or resistance. Those regions with copy number differences between drug sensitive and resistant cell lines are then examined on the gene expression level for cancer gene deregulation.
Results:
156 chromosomal regions of recurrent copy number alteration are identified across the cell line panel. 15 compounds are associated with differential copy number between sensitive and resistant cell lines in one or more of these regions for a total of 77 significant drug-region associations. Out of these 77 associations, 13 of the regions also include genes which are differentially expressed between the sensitive and resistant cell lines.
Conclusions:
Genes that are deleted in drug sensitive or drug resistant cell lines can act as biomarkers for drug sensitivity or resistance respectively. Similarly, genes amplified in drug sensitive cell lines can act as biomarkers for drug sensitivity. Genes amplified in drug resistant cell lines provide hypotheses for combination therapy, as we believe that the amplification that is seen only in the drug resistant cell lines is a driving factor causing the resistance to that drug. Using the drug along with pharmacological inhibition or experimental knockdown of the gene commonly amplified in the resistant cell lines is hypothesized to alter the cell lines from a drug resistant to a drug sensitive state. Novel combination therapies for use in given drug resistant cell lines harboring specific amplifications are currently being validated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2179.
Abstract 218: Ginsenoside Rh2 induced bcl2 family proteins mediated apoptosis in vitro and xenograft in vivo
Authors: Choi Sunga , Oh Jun-Young , Song Jung-A , Kim Soo-Jin 
Published: February 2011

Abstract
Natural products have received increasing attention in recent years for the discovery of novel cancer preventive and therapeutic agents. The root of Panax ginseng has been used for thousands of years in Korean medicine practice for treatment of diverse ailments. More recent studies have indicated that ginsenoside saponins, a constituents of Panax ginseng can induce retardation of growth and cell death of cancer in culture and in vivo. In this study, we used two human breast cancer cells, MCF7 (wild type p53, ER responsive), MDA-MB-231 (mutated p53, ER-independent) and xenograft nude mouse model to investigate further insights into the mechanism of Ginsenoside Rh2-induced cell death. It was observed that Rh2 treatment significantly decreases viability at 40 to 60 μM concentrations as judged by trypan blue dye exclusion assay in both two cell lines. Rh2 treatment also increased in a concentration- and time-dependent cell death in cytoplasmic histone-associated DNA fragmentation assay. Bcl-2 family proteins have emerged as critical regulators of apoptosis by functioning either as promoters (e.g., Bax and Bak) or inhibitors (e.g., Bcl-2 and Bcl-xL) of the cell death process. Rh2-induced apoptosis was correlated with induction of Bax and Bak and a decrease in Bcl-xL and Bcl-2 protein levels in both two cell lines. Transient transfection of MCF7 cells with Bak- and Bax-targeted siRNAs conferred partial yet significant protection against ginsenoside Rh2-induced apoptosis. The increased expression level of Bax was associated with initiation of intrinsic apoptotic pathway. The pathway initiated translocation of Bax from cytosol following release of mitochondrial cytochrome c dependent on ginsenoside Rh2 treatment time. To test whether Rh2-mediated inhibition of MDA-MB-231 xenograft growth in vivo at the 2mg dose was due to increased apoptosis, tumor tissues from control and Rh2-treated mice were examined for histologic evidence of apoptosis. The tumors from Rh2-treated mice exhibited markedly higher count of apoptotic bodies and reduced proliferation index. The tumor section also exhibited the changed protein level compared with control one in specific for Bax or Bcl-2 immunohistochemistry. It was consistent in RT-PCR using appropriate Bcl2- family gene primers. In conclusion, our data suggests Rh2-mediated suppression of MDA-MB-231 xenograft growth in vivo and MF7 cells in vitro highly correlates with increased apoptosis. The results of the present study show that the ability of Rh2 to inhibit cell growth or cause apoptotic cell death in two human breast cancer cells is not influenced by either p53 functional status or ER responsiveness.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 218.
Abstract 2185: Identification of novel compounds that preferentially kill repair deficient cells using high-throughput screening
Authors: Peterson-Roth Elizabeth , Abriola Laura , Merkel Jane , Glazer Peter 
Published: February 2011

Abstract
Loss of functional DNA repair pathways is a common occurrence in cancer cells and discovery of novel drugs that selectively kill repair deficient tumors cells could identify new cancer therapies. In this work we describe the use of high-throughput screening to determine chemicals that sensitize cells deficient in the fanconi anemia protein, FANCD2. Cell growth of human fibroblasts proficient (PD20+D2) and deficient (PD20) for FANCD2 were screened using two libraries containing over 1000 bioactive compounds and kinase inhibitors. The cells were treated with compounds continuously for 3 days and cell growth was assessed using a luciferase-based assay measuring ATP levels. The initial screen identified numerous compounds inducing differential survival in cells with and without FANCD2 and follow-up testing will be required to confirm these potential hits. However, it is promising that, in addition to novel compounds, several crosslinking agents, including mitomycinC, which are known to sensitize fanconi anemia cells to cell death are among the positive hits. Our results validate chemical screening as a tool to discover potential new cancer therapies targeting repair deficient cells lines. In addition, other than their role in crosslink repair, there is still not much known about the fanconi anemia protein family and the discovery of novel compounds involved in FANCD2 dependent cell survival could lead to the discovery of new functions of this protein family.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2185.
Abstract 2188: A high throughput RNAi screen for regulators of thioredoxin in pancreatic cancer cells identifies components of TGFβ-signaling as inducers of thioredoxin expression
Authors: Grandjean Geoffrey , Bartholomeusz Geoffrey , Kingston John , Powis Garth 
Published: February 2011

Abstract
Thioredoxin (Txn), thioredoxin reductase (TxnR) and NADPH comprise a thioredoxin system which exists in nearly all living cells functioning in multi-facetted processes in mammalian cells. These include thiol-dependent thiol-disulfide exchange reactions crucial to control the redox homeostasis, cellular growth, defense against oxidative stress and control of apoptosis. Thioredoxin expression has been observed to be elevated in some types of human cancer and has been shown to confer resistance to chemotherapy or radiation-induced apoptosis. It has also been shown that elevated levels of thioredoxin contribute to the carcinogenic process and invasive phenotype of cancer. Identifying key inducers of thioredoxin expression in cancer cells will permit us to specifically target these components with the goal of improving the clinical outcome of treatment of patients with thioredoxin overexpressing cancers. Here, we describe a functional genomic screen designed to identify inducers of thioredoxin expression in which a library of 7040 small interfering RNAs (targeting human kinome and druggable genes) was screened for their ability to block the expression of endogenous thioredoxin in the pancreatic cancer cell line, MiaPaCa2. The primary screen identified numerous potential inducers of thioredoxin expression and, through the use of extensive validation of all these potential hits, yielded 21 high confidence genes that have not previously been associated with the induction of thioredoxin expression. Six of these target genes were associated with TGFβ signaling and selected for this study. Downregulation of these genes strongly inhibited the expression of endogenous thioredoxin in the MiaPaCa pancreatic cancer and other cancer cell lines. Moreover, treating MiaPaCa2 cells with TGF-β1 induced the expression of thioredoxin. TGF-β1-induced expression of thioredoxin is mediated through SMAD2, SNL2, ITGAV, ITGb3 and SP1 thus showing that our study uncovers new aspects of thioredoxin regulation. Collectively, these observations offer several insights on how thioredoxin mediates tumor growth and demonstrates the utility of large-scale RNAi screens in mammalian cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2188.
Abstract 2191: Development of a phylogenetic tree model to investigate the role of genetic mutations in a single endometrial tumor
Authors: Dai Donghai , Beck Brandon B. , Zhang Guoyi , Luo Wentao , Wu Fan , Kingsmore Stephen F. 
Published: February 2011

Abstract
Modern genome sequencing technology has identified thousands of mutations in human tumors, but analysis of the role of genetic mutations in tumor development, utilizing prevalence information from many tumors, has yet to define in patients the functional contribution of genetic mutations, individually and collectively. To understand the genetic basis of human endometrial cancer, the fourth most common cancer in women, transcriptome sequencing was performed on an endometrial tumor paired with normal cervical tissue, and 26 non-synonymous somatic mutations were confirmed in the tumor genome DNA. A phylogenetic tree illustrating the mutational timeline was developed based upon the distribution of 26 mutations in 30 randomly-selected laser-captured single cells from the tumor sections. Five ubiquitous mutations were identified that are presumed to occur in the cancer founder cell of the tumor, which may collectively play critical roles in endometrial oncogenesis. However, further testing in 10 additional endometrial tumors failed to show overlapping mutations, indicating the lack of a single common oncogenic pathway for these endometrial tumors.
Furthermore, we developed a mathematical and phylogenetic calculation of the cell population produced by a mutated ancestor cell, which quantifies the role of tumor-specific individual genetic mutations in cancer cell proliferation in a single resected patient tumor, without relying on prevalence information from other patients. This novel approach will be further tested in a larger sample set to determine whether multiple genetic mutations’ quantitative contributions can be used to predict patient outcomes.Functional contribution of individual mutationsmutant genesgenetic timeoffspring (million cells)ScoreC10orf26, GMPPA CREBL1 PPP2R2D SLCO2A13010000.997DDEF1 LOC728069298330.025LDLRAP1 PLEC129167−0.06MYST1286670.025GORASP2 ILKAP, LOC72942328100−0.07INCENP, ME22867−0.09PDZD8274000.011AP1G227267−0.01POLE4, SDC2263000.025PIF1, XYL226100−0.04TOR3A251670.01LOC642934251330CCDC50, CIZ12467−0.01LOC645634241000.014
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2191.
Abstract 2192: Functional genomic screen to identify candidates capable of modulating invasive properties of HNSCC
Authors: Lepikhova Tatiana N. , Imai Misa , Peitsaro Nina , Klefstrom Juha , Monni Outi M. 
Published: February 2011

Abstract
Head and neck squamous cell carcinomas (HNSCC) contain a heterogeneous population of cancer cells some of which is explained by ongoing mutations that occur due to genetic instability and environmental factors. Not all of the cancer cells have a similar ability to drive tumor formation. To identify genes capable of modulating invasive properties in head and neck squamous cell carcinoma (HNSCC), we have compared copy number profiles (244K aCGH) of 12 primary and metastatic cancer cell lines obtained from patients with HNSCC of tongue and larynx. A specific pattern of copy number gains and losses was present in each cell line studied. Majority of the changes occurred in both the primary tumor and corresponding metastasis, but some amplifications, such as 10q21.1., 11q22, and 17p12 occurred more frequently in metastatic cancers. To determine whether any genes located at the amplicons input to metastatic potential of HNSCC we are performing a systematic loss-of-function survey. First, we examined the cell growth and invasive properties of primary and metastatic cell lines in vitro and in vivo. We then set up a genetic screen using highly metastatic cell lines in in vitro invasion assay system. pLKO1 shRNA library targeting genes located at identified amplified regions in invasive cells were transduced into the selected cell lines and transduced cell lines were subjected to transwell invasion assay. Several genes targeted for amplification and capable of modulating invasive properties of HNSCC in vitro have been selected for further validation in vivo.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2192.