bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3157: Loss of heterozygosity as a molecular ‘second hit’ In familial pancreatic cancer.
Authors: Kanji Zaheer S. , Serra Stefano , Holter Spring , Borgida Ayelet , Grant Robert , Gallinger Steven 
Published: August 2014

Abstract
BACKGROUND/HYPOTHESIS: Familial Pancreatic Cancer (FPC) has an autosomal dominant, variable penetrant mode of inheritance with &gt;80% of its genetic cause yet to be discovered. We hypothesize that a high density DNA microarray analysis of Formalin-Fixed Paraffin Embedded (FFPE) FPC tumors will yield novel regions of genomic loss harboring disease causing FPC gene(s).
METHODS: 158 FFPE FPC tumor specimens with matched normal tissue were reviewed by a pancreatic pathologist and tumors with &lt;70% cellularity underwent laser capture microdissection. The samples with &gt;70% cellularity were microdissected directly from marked unstained slides. A total of 74 samples were DNA extracted, whole genome amplified and processed on the Affymetrix 660K Oncoscan Microarray. Copy number analysis was performed using Nexus Copy Number Variation Version 6.1 software employing the SNP-FASST2 segmentation and Allele Specific Copy Number Analysis of Tumors (ASCAT) algorithms.
PRELIMINARY RESULTS: A pair-wise analysis of 55 FPC samples with matched normal tissue was performed. Recurrent regions of loss of heterozygosity (LOH) were known loci of importance in pancreatic tumorigenesis, including CDKN2A, p53 and SMAD4. Copy neutral/gain LOH was observed throughout the genome and may account for &gt;35% of chromosomal loss. Recurrent novel genetic loci displaying LOH was observed on chromosomes: 3p(25%), 5q(18%), 6p(22%), 12q(18%) and Xq (42%). Examination of 2 FPC siblings elucidates shared loss regions spanning the 3p22.2-3p22.3 and 17p13.3 loci. Candidate tumor suppressor genes (TSGs) of interest include DCLK3, SERPINF1, SERPINF2 and SMYD4.
CONCLUSION: We have described for the first time the presence of copy neutral/gain LOH in FPC highlighting previously unknown regions displaying genetic loss. Further confirmation with quantitative PCR, integrating with germline exome sequencing data, and validation of putative TSGs shared by members of high risk FPC kindreds will help uncover novel genes associated with this disease.
Citation Format: Zaheer S. Kanji, Stefano Serra, Spring Holter, Ayelet Borgida, Robert Grant, Steven Gallinger. Loss of heterozygosity as a molecular ‘second hit’ In familial pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3157. doi:10.1158/1538-7445.AM2013-3157
Abstract 3158: Transcription factor SOX11 decreases viability in ovarian carcinoma cells.
Authors: St. Clair Caryn M. , Wethington Stephanie L. , Bisogna Maria , Dao Fanny , Jelinic Petar , Levine Douglas A. 
Published: August 2014

Abstract
Objective: The Cancer Genome Atlas (TCGA) evaluated nearly 500 advanced serous ovarian carcinomas and identified four gene expression subclasses. The transcription factor SOX11 was markedly overexpressed in the proliferative subtype and associated with phosphorylation of other cell cycle related proteins including CHEK2, WWTR1, and EIF4EBP1. We tested the hypothesis that over-expression of SOX11 will decrease proliferation of ovarian cancer cells through transcriptional repression.
Methods: SOX11 was overexpressed via lipofectamine transfection in the TP53 wild-type ovarian cancer cell line SKOV3 and the TP53 mutated ovarian cancer cell line OVCAR3. Cell proliferation was assessed 48 hours after transfection using the VisionBlue fluorescence-based viability assay. Cell cycle analysis was performed utilizing a propidium iodide (PI) assay followed by fluorescence-activated cell sorting (FACS). Finally migration of SOX11-transfected cells was analyzed in comparison to mock-transfected controls via monolayer scratch assay.
Results: Successful overexpression of the SOX11 protein was confirmed using GFP fluoroscopy and western blot 24 and 48 hours following transfection. Cell viability was reduced by 14-63% at 48 hours in SOX11-transfected SKOV3 cells compared to mock controls (P = 0.01) in a dose dependent fashion. Cell cycle was unaffected by SOX11 overexpression. Finally, the monolayer scratch assay demonstrated that cells overexpressing SOX11 migrated more slowly than mock controls (median velocity 3.92 vs. 6.19 um/hr, P = 0.001). Data from OVCAR3 cells are currently being analyzed and will be presented.
Conclusions: Overexpression of SOX11 resulted in decreased cell viability without affecting cell cycle. Further studies will assess the mechanism of this decreased viability which may involve diversion toward an apoptotic pathway when SOX11 is overexpressed or regulation by transcription repressors such as WWTR1. SOX11 suppression has been shown in lymphoma to be associated with more aggressive tumors through mechanisms associated with lysophosphatidic acid growth regulation, offering mechanistic associations with ovarian cancer. Ongoing work will determine the relationship between SOX11 and TP53 mutation frequently found in high-grade serous carcinoma. These studies will help to explain the differential outcomes seen across high-grade serous ovarian carcinoma.
Citation Format: Caryn M. St. Clair, Stephanie L. Wethington, Maria Bisogna, Fanny Dao, Petar Jelinic, Douglas A. Levine. Transcription factor SOX11 decreases viability in ovarian carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3158. doi:10.1158/1538-7445.AM2013-3158
Abstract 3160: Open-source RNAi genetic screen platform: discovery of drug targets in cancer cell models.
Authors: Komarov Andrei , Makhanov Mikhail , Komarova Elena , Novototzkaja Lilya , Yeluashvili Michael , Suchkov Dmitry , Bonneau Kyle , Tedesco Donato , Frangou Costa G. , Diehl Paul , Deng Debbie , Hyder Karim , Komarov Pavel , Gudkov Andrei , Chenchik Alex 
Published: August 2014

Abstract
We have developed an open-source RNAi genetic screening technology, funded in part by NIH grants and freely available to the scientific community. This platform can be used for functional discovery of drug targets associated with viability and regulation of signaling pathways in cancer cells. Here we present a novel, free public resource for genome-wide RNAi screens: DECIPHER pooled lentiviral shRNA libraries. Results are shown from two RNAi screens with DECIPHER shRNA libraries: one “drop-out” screen to identify genes essential for viability in a panel of leukemic cells, and a second “rescue” screen to identify genes required for FAS induced apoptosis. Both screens found a combination of known and novel signaling pathway and regulatory genes whose functions were confirmed to be required to produce the biological responses. From the viability screens in the panel of leukemia cell lines, subsequent validation using single shRNA-expressing constructs showed that about 80% of the shRNAs identified in each complex library screen did in fact lead to cell death when transduced in cells. Analysis of the identified essential genes for known biological interactions revealed non-random clusters of interacting proteins that provide a useful strategy for prioritization of potential targets. Analysis of the lethal combinations indicates redundant, complementary, and compensatory responses in cancer cells. In the case of the FAS-induced apoptosis, in vitro screening data also enabled us to select targets that protected mice from FAS-induced hepatic failure. These results demonstrate that complex pooled shRNA libraries provide a highly efficient, flexible, and cost-effective alternative to array-based RNAi screening methods for identifying genes regulating biological responses and possible new therapeutic targets.
Citation Format: Andrei Komarov, Mikhail Makhanov, Elena Komarova, Lilya Novototzkaja, Michael Yeluashvili, Dmitry Suchkov, Kyle Bonneau, Donato Tedesco, Costa G. Frangou, Paul Diehl, Debbie Deng, Karim Hyder, Pavel Komarov, Andrei Gudkov, Alex Chenchik. Open-source RNAi genetic screen platform: discovery of drug targets in cancer cell models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3160. doi:10.1158/1538-7445.AM2013-3160
Abstract 3165: Metastatic tumor evolution delineates clinically important oncogenic drivers in diffuse gastric cancer.
Authors: Nadauld Lincoln D. , Garcia Sarah , Natsoulis Georges , Bell John M. , Hopmans Erik , Xu Hua , Pai Reetesh K. , Regan John F. , Ford James M. , Kuo Calvin J. , Ji Hanlee 
Published: August 2014

Abstract
We conducted a detailed genetic and functional analysis of personalized tumor evolution in a case of diffuse gastric cancer. Leveraging the unique genetics of an individual with a confirmed germline mutation in the causative CDH1 tumor suppressor gene, we identified candidate drivers for a primary tumor in the stomach and a metastatic recurrence in the left ovary, referred to as a Krukenberg tumor. Using genome sequencing, we demonstrate that the primary and metastatic tumors share the majority of cancer driver events including biallelic CDH1 and TP53 mutations consistent with a common genetic origin. The primary gastric cancer displayed amplification of FGFR2, a gene that encodes the fibroblast growth factor (FGF) receptor 2 with multiple small molecule inhibitors in clinical therapy development. Tumor evolution and genetic divergence was clearly evident with the ovarian metastasis lacking the FGFR2 amplification and displaying its own subset of mutations and genomic aberrations. Namely, the metastatic tumor had unique biallelic events affecting TGFBR2, a critical gene in the TGF-β (tumor growth factor) signaling pathway that has not previously implicated in diffuse gastric cancer. To determine the independent oncogenic attributes of these separate pathways, we used a diffuse gastric cancer cell line and organoid model system to replicate and study the context of the known and candidate drivers found in the index patient's primary versus metastatic sites. We demonstrated that in the context of biallelic CDH1 and TP53 functional loss, the addition of either FGFR2 or TGFBR2 drivers independently lead to gastric cancer. This result supports the independent cancer driver roles of the FGF and TGF-β signaling pathways in metastatic tumor evolution in diffuse gastric cancer. Our study has implications regarding personalized cancer medicine approaches in patients with metastatic gastric cancer.
Citation Format: Lincoln D. Nadauld, Sarah Garcia, Georges Natsoulis, John M. Bell, Erik Hopmans, Hua Xu, Reetesh K. Pai, John F. Regan, James M. Ford, Calvin J. Kuo, Hanlee Ji. Metastatic tumor evolution delineates clinically important oncogenic drivers in diffuse gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3165. doi:10.1158/1538-7445.AM2013-3165
Abstract 317: Role of ATM and PTEN in prostatic carcinogenic dog prostate: validation of aCGH results.
Authors: Fonseca Alves Carlos E. , Pellicciari Patricia R. , Rodrigues Marcela M. P. , Rogatto Silvia R. , Amorim Renee L. 
Published: August 2014

Abstract
The canis lupus familiares is the only species besides human that spontaneously develop prostatic carcinoma (PCa). In addition, the metastatic sites are similar to those frequently reported in men. For these reasons, the dog is the best natural model to study the molecular mechanisms in PCa development providing a natural animal model for treatment by molecular targets. Previously, we investigated copy number alterations by arrayCGH (Canine Genome CGH Microarray 4x44K-G2519F, Agilent Technologies) in canine prostatic lesions: 3 benign prostatic hyperplasias (BPH), 4 proliferative inflammatory atrophies (PIA), and 14 PCa. Five histologically normal prostatic tissues were used as reference. Genomic alterations were evaluated using Genomic Workbench Standard Edition 5.0.14. This previous study revealed significant copy number losses of Atm and Pten exclusively in PCa. In the present study, ATM and PTEN immunoexpression were investigated using a tissue microarray (TMA) containing 149 canine prostatic paraffin-embedded lesions (BPH, PIA and PCa) collected from 67 animals. Immunohistochemical reactions were performed using the polyclonal rabbit antibody anti-PTEN (Santa Cruz Biotech, 1:50) and anti-ATM (Abcam, 1:50). The sections were developed with diaminobenzidine (DAB) and peroxidase. The immunohistochemical staining was assessed in each core by the distribution of positive cells for each antibody per lesion (score 1: &lt;25% cells positive, 2: 26% to 50%, 3: being 51% and 75% and 4:&gt; 75%) and intensity (1: weak, 2: moderate, 3: intense). Chi-square or Fisher exact test was used to determine the association between the categorical variables using GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA). Distribution of positive cells did not differ among lesions. PCa and PIA showed more samples with weak intensity for ATM when compared to normal prostatic tissue and BPH (PCa: p=0,032 and PIA: p=0,025). Benign prostatic hyperplasia and normal samples presented intense PTEN immunostaining than PCa (p=0,021) and PIA (p=0,0013). These results suggest that ATM and PTEN proteins expression in canine prostatic carcinoma are downregulated possibly by copy number losses. These findings are similar from those described in prostate carcinomas from human corroborating for the use of dogs as a natural model to study prostatic disease in men.
Citation Format: Carlos E. Fonseca Alves, Patricia R. Pellicciari, Marcela M. P. Rodrigues, Silvia R. Rogatto, Renee L. Amorim. Role of ATM and PTEN in prostatic carcinogenic dog prostate: validation of aCGH results. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 317. doi:10.1158/1538-7445.AM2013-317
Abstract 3172: Pooled RNAi screens in xenograft mouse models.
Authors: Tedesco Donato , Bonneau Kyle , Makhanov Mikhail , Deng Debbie , Diehl Paul , Sun Peiqing , Chenchik Alex 
Published: August 2014

Abstract
We present results of clonal analysis studies aimed at characterizing the heterogeneity of in vivo cancer cell growth in xenograft models. Using a high-throughput sequencing method, we followed the fate of thousands of individually bar-coded cancer cells grown in vitro, or in vivo upon sub-cutaneous implantation in immunocompromised mice. By precisely and reproducibly quantifying clonal cancer cell growth in vivo, we found that xenograft growth is marked by a phenomenon of clonal dominance, in which a small subset of cancer cell sub-clones account for the bulk of the resulting tumor mass. This phenomenon has important implications for the field of in vivo shRNA screening. Subsequently, we developed a new proprietary clonal RNAi screening platform specifically designed to circumscribe the clonal dominance effect in xenograft model viability screens. We used this technology to perform xenograft “drop-out” screens in a panel of tumorigenic cell lines, including human breast, ovarian and colon carcinomas. Preliminary data will be presented. These results demonstrate that complex pooled shRNA libraries provide a highly efficient, flexible, and unique tool for in vivo screens aimed the discovery of potential cancer therapy targets.
Citation Format: Donato Tedesco, Kyle Bonneau, Mikhail Makhanov, Debbie Deng, Paul Diehl, Peiqing Sun, Alex Chenchik. Pooled RNAi screens in xenograft mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3172. doi:10.1158/1538-7445.AM2013-3172
Abstract 3177: Web-based access using CellMiner for gene expression, DNA copy number, microRNA transcript levels, variant status, drug activity, and their pattern comparisons for the NCI-60.
Authors: Reinhold William C. , Sunshine Margot , Varma Sudir , Liu Hongfang , Abaan Ogan , Meltzer Paul , Morris Joel , Kohn Kurt , Doroshow James , Pommier Yves 
Published: August 2014

Abstract
High-throughput data is increasingly being integrated into the fields of biology, molecular biology, and pharmacology. However, a difficult problem has been the rapid and fluid access to and integration of the data, which tends to reside in huge unwieldy databases. One set of cell lines with substantial potential for benefit from this type of access and integration is the NCI-60 cancerous cell lines. We present here a set of tools within our CellMiner web-application designed to address this need for the areas of transcript expression, microRNA expression, gene DNA copy number, variant status, and drug activity. CellMiner allows the user to rapidly access data for relative levels of transcript expression for 26,065 genes, 360 microRNAs, and 20,602 compounds including 102 Food and Drug Administration (FDA)-approved drugs. These levels in turn create patterns across the NCI-60 that can be compared to one another using our “pattern match” tool. Together, these tools allow one to query the data for potential relationships between these parameters, in a manner specific to a users area of expertise and interest, in a rapid and flexible manner without the need for expertise in computer science or bioinformatics. Comparisons of transcript/drug will be demonstrated with SLFN11/topotecan; variant/drug with BRAF V600E/vemurafinib; colon tissue-of origin specific genes with TRIM15, RNF43, and VIL1; and DNA copy number change with CDKN2A (p16). The data are publicly available at http://discover.nci.nih.gov/cellminer.
Citation Format: William C. Reinhold, Margot Sunshine, Sudir Varma, Hongfang Liu, Ogan Abaan, Paul Meltzer, Joel Morris, Kurt Kohn, James Doroshow, Yves Pommier. Web-based access using CellMiner for gene expression, DNA copy number, microRNA transcript levels, variant status, drug activity, and their pattern comparisons for the NCI-60. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3177. doi:10.1158/1538-7445.AM2013-3177
Abstract 3179: The head and neck cancer biomarker wiki: A tool for data mining and biomarker meta-analyses.
Authors: Ceder Rebecca , Kohonen Pekka , Grafström Roland C. 
Published: August 2014

Abstract
Biomarkers that accurately predict outcome or treatment response is lacking for most human tumor types, including for common and well-studied cancers like head and neck squamous cell carcinoma (HNSCC). With the aim to summarize existing genomic analysis and biomarker data into a format analyzable with bioinformatics processing tools, we set out to develop a biomarker wiki for HNSCC, hypothesizing that meta-analyses would reveal novel and potentially clinically useful sets of biomarker genes. We applied the user-friendly MediaWiki interface for collecting data in the public domain, and separated the results under the categories: primary tumor profiling, metastasis profiling, cell line profiling and treatment response. The information was captured applying controlled and standardized vocabularies, including with data storage in the multi-omics Investigation/Study/Assay (ISA-Tab) format. Bioinformatics-driven meta-analyses of results from currently over 50 publications indicate that the wiki serves to accurately identify common gene patterns, gene ontologies, molecular networks and key regulator genes within and among the respective categories. Additionally, independent validations relative other databases such as the Human Gene Expression Map, the Human Protein Atlas and the cBio Cancer Genomics Portal confirm many associations, including with significant correlations to poor outcome for gene sub-sets. Overall, the wiki results so far agree with the hypothesis under testing, suggesting novel biomarker genes/signatures for future clinical assessment. On completion, we foresee a query-enabling update-friendly knowledge platform for head and neck cancer studies in the public domain.
Citation Format: Rebecca Ceder, Pekka Kohonen, Roland C. Grafström. The head and neck cancer biomarker wiki: A tool for data mining and biomarker meta-analyses. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3179. doi:10.1158/1538-7445.AM2013-3179
Abstract 318: Preclinical evaluation of monoclonal antibody H6-11 for prostate cancer imaging.
Authors: Jin Hongjun , Xu Mai , Padakanti Prashanth K. , Tu Zhude 
Published: August 2014

Abstract
Altered post-translational modification (PTM) of glycosylations to various nuclear and cytosolic proteins is a universal feature of cancer cells and these modified glycan plan significant role in immune surveillance, tumor invasion, and increase malignancy. In this study, we reported a novel monoclonal antibody reacting to the tumor glycoproteins with molecular weight around 40-60 kDa. Deglycosylation examination suggested the antigenic isotope of the glycan is O-linked β-N-acetylglucosamine (O-GlcNAc) group. We examined the reactivity of H6-11 to cancer cells including PC-3, MCF-7 cells and implanted PC-3 and EMT-6 tumor tissues using immunofluorescence staining and autoradiography technique. The Zr-89 labeled H6-11 was successfully synthesized and the microPET study was performed in PC-3 xenograft prostate model in nude mice. microPET study showed that significant amount of radioactivity accumulation was observed in the excretory organs during the early period post-injection of radioactivity. At 24 hrs post-injection of radioactivity, significant amount of radioactivity was observed in the xenograft prostate tumor, while the radioactivity intensity was decreased in the liver and kidney. Radioactivity uptake in the tumor was still evident at 120 hrs post-injection of radioactivity. Our work suggested that the H6-11 antibody is capable of detecting prostate tumors both in vitro and in vivo.
Citation Format: Hongjun Jin, Mai Xu, Prashanth K. Padakanti, Zhude Tu. Preclinical evaluation of monoclonal antibody H6-11 for prostate cancer imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 318. doi:10.1158/1538-7445.AM2013-318