bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5327: Using CellMiner for gene expression, DNA copy number, microRNA transcript levels, variant status, drug activity, and their integration for systems pharmacology for the NCI-60
Authors: Reinhold William C. , Sunshine Margot , Varma Sudir , Morris Joel , Kohn Kurt , Doroshow James , Pommier Yves 
Published: May 2015

Abstract
Molecular biology and pharmacology are being transformed by high-throughput data. Access, and integration of this data, however, remains difficult. The NCI-60 cancerous cell lines are arguably the premier model for data integration and systems pharmacology. To make this data accessible for both bioinformaticists and non-bioinformaticists, we have developed the CellMiner set of web-based tools (http://discover.nci.nih.gov/cellminer). These tools currently or in the near future will provide “Cell line signatures” for gene and microRNA transcript expression, DNA copy number variation, genetic variation, and drug or compound activity. This data includes relative levels of transcript expression for 26,065 genes, 360 microRNAs, activities of 19,940 compounds including 110 Food and Drug Administration (FDA)-approved and 53 in clinical trial drugs, and percent conversions of 16,381 genetic variants (both germline and somatic). Current or upcoming tools facilitating the combination of this data include i) “Pattern comparison”, which provides correlations to a users input pattern to transcript and microRNA expression and compound/drug activity, ii) “Cross correlation”, which provides all correlations between up to 150 input genes, microRNAs, and compounds or drugs, iii) “Genetic variation versus drug visualization”, which provides a rapid visualization of potential drug: gene DNA variant relationships, and iv) “Genetic variant summation”, which provides a synopsis of mutational burden on any pathway of interest for up to 150 genes. These tools allow the user to flexibly query the data for potential relationships between molecular and pharmacological parameters, in a manner specific to that users area of expertise and interest.
Citation Format: William C. Reinhold, Margot Sunshine, Sudir Varma, Joel Morris, Kurt Kohn, James Doroshow, Yves Pommier. Using CellMiner for gene expression, DNA copy number, microRNA transcript levels, variant status, drug activity, and their integration for systems pharmacology for the NCI-60. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5327. doi:10.1158/1538-7445.AM2014-5327
Abstract 533: MicroRNA486-5p is a KRas target involved in promoting cell proliferation in lung cancer
Authors: Aoki Mateus N. , Salviatto Amanda C. P. , Lobo Tatiana C. C. , Carreira Ana Cláudia O. , Sogayar Mari C. , Basseres Daniela S. 
Published: May 2015

Abstract
KRAS-induced lung cancer is a very common disease, for which there are currently no effective therapies. Direct targeting of KRAS has failed in clinical trials and intense efforts are underway to identify KRAS targets that play a crucial role in oncogenesis. One promising KRAS-regulated pathway that has so far been overlooked is the microRNA pathway. Even though many microRNAs that regulate expression of KRAS are known, microRNAs regulated by oncogenic KRAS remain largely unknown. Our goal was to identify microRNAs regulated by oncogenic KRAS in lung cells that could contribute to the oncogenic phenotype. Due to a reported positive correlation between microRNA486-5p (miR-486-5p) expression and the presence of KRAS mutations in colon cancer specimens, we decided to investigate in lung cells whether KRAS regulates miR-486-5p. For that purpose we used an immortalized human primary lung epithelial cell line (SALEB) and its isogenic KRAS-transformed counterpart (SAKRAS), as well as lung cancer cell lines with either gain-of-function or loss-of-function of KRAS. We found, in all models tested, a positive correlation between expression of oncogenic KRAS and expression of miR-486-5p. We also found a negative correlation between expression of oncogenic KRAS and expression of miR-486-5p targets, including FoxO1, a tumor suppressor. In order to evaluate how miR-486-5p affects Ras-induced oncogenic properties, we transfected miR-486-5p inhibitor oligonucleotides into KRAS-positive lung cancer cell lines H358 and A549. Inhibition of miR-486-5p expression leads to reduced growth in clonogenic assays and reduced MTT viability. This reduction is not associated with increased cell death, but, as measured by 3H-Thymidine incorporation, it is associated with decreased cell proliferation. Interestingly, transfection of miR-486-5p double-stranded RNA mimic oligonucleotides into KRAS negative lung cancer cell line H1703 or into H358 cells with loss of function of KRAS by RNA interference leads to enhanced proliferation and clonogenicity. Taken together, these results indicate, not only that miR-486-5p is a KRAS target in lung cancer, but also that miR-486-5p acts as an oncomiR contributing to KRAS-induced cell proliferation. Further understanding of miR-486-5p targets could uncover novel pathways for KRAS-induced lung cancer therapy design.
Citation Format: Mateus N. Aoki, Amanda C. P. Salviatto, Tatiana C. C. Lobo, Ana Cláudia O. Carreira, Mari C. Sogayar, Daniela S. Basseres. MicroRNA486-5p is a KRas target involved in promoting cell proliferation in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 533. doi:10.1158/1538-7445.AM2014-533
Abstract 5331: GenomeSpace: An environment for frictionless bioinformatics
Authors: Reich Michael M. , Liefeld John , Ocana Marco , Jang Donkeung , Robinson James , Carr Peter , Hill Barbara , Tabor Thorin , Thorvaldsdottir Helga , Regev Aviv , Mesirov Jill P. 
Published: May 2015

Abstract
Over the past several years, cancer genome characterization initiatives such as The Cancer Genome Atlas and the International Cancer Genome Consortium have produced an explosion of genomic data. These efforts, together with the proliferation of repositories for small-molecule screens and large-scale data production efforts to discover the breadth of genomic variation in humans, offer a new era of potential for the understanding of the basic mechanisms of cancer and identification of novel treatments.
Comprehensive analysis of these datasets requires the coordinated use of Web-based applications and data repositories, desktop analysis tools and visualizers, and single-purpose algorithms. However, the effort required to transfer data between tools, convert between data formats, and manage results often prevents researchers from utilizing the wealth of methods available to them. Many integrative genomics and translational “bench to bedside” discoveries are possible with combinations of existing tools, but the necessary transitions between them puts them out of the reach of most researchers.
GenomeSpace, http://www.genomespace.org, is an environment that brings together diverse computational tools, enabling scientists without programming skills to easily combine their capabilities. It aims to offer a common space to create, manipulate and share an ever-growing range of genomic analysis tools. GenomeSpace features support for cloud-based data storage and analysis, multi-tool analytic workflows, automatic conversion of data formats, and ease of connecting new tools to the environment. A set of six “GenomeSpace-enabled” seed tools developed by collaborating organizations provides a comprehensive platform for the analysis of cancer data: Cytoscape (UCSD), Galaxy (Penn State University), GenePattern (Broad Institute), Genomica (Weitzmann Institute), Integrative Genomics Viewer (Broad Institute), and the UCSC Genome Browser (UCSC). Its open architecture has driven its adoption by a number of additional tools, including ArrayExpress, Cistrome, the Cancer Cell Line Encyclopedia, Project Achilles Portal, and Multiple Myeloma Genomics Portal, with new tools and resources being released regularly.
We show how researchers can use GenomeSpace to effortlessly combine the capabilities of all of these tools in several cancer research scenarios.
Citation Format: Michael M. Reich, John Liefeld, Marco Ocana, Donkeung Jang, James Robinson, Peter Carr, Barbara Hill, Thorin Tabor, Helga Thorvaldsdottir, Aviv Regev, Jill P. Mesirov. GenomeSpace: An environment for frictionless bioinformatics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5331. doi:10.1158/1538-7445.AM2014-5331
Abstract 5332: Comparison of variant calling from whole exome and transcriptome sequencing using CLC Cancer Research Workbench
Authors: Arens Anne , Hein Anne-Mette K. , Appelt Uwe , Joecker Anika , Mønsted Søren , Knudsen Bjarne , Thomson Naomi , Lussier Richard , Boysen Cecilie , Forsberg Roald 
Published: May 2015

Abstract
The now commonplace application of whole exome and genome sequencing in cancer research and diagnostics has allowed for rapid identification of SNPs and InDels in protein coding regions, but neither method is able to reveal situations of incomplete penetrance. That is, while possible cancer causing allele variants can be detected with these methods, this does not mean these alleles are actually expressed. Reasons for this are various and include epigenetic effects and changes, transcription regulation mechanisms, mRNA degradation and epistasis. By contrast, transcriptome sequencing (RNA-seq) can be used to identify the alleles being expressed. This method has the additional benefits of providing insight into the transcript expression levels, expressed allele isoforms and offers the possibility of identifying instances of fusion transcripts. Such knowledge about variants expressed in tumor cells is crucial for the identification of effective drug targets.
Here, we illustrate the benefits of combining whole exome sequencing with RNA-seq by analyzing whole exome and RNA-seq datasets from uveal melanoma samples with our newly developed CLC Cancer Research Workbench. This software suite enables the complete analysis of both approaches, including variant calling, followed by the comparison of the called variants. The analysis will be carried out using user-friendly, automated workflows distributed with the CLC Cancer Research Workbench. In this work, we discuss and compare variants identified in the exome and RNA-seq datasets using our algorithms, and focus particularly on variants identified in the exome data that appear not to be expressed in the tumor samples.
Citation Format: Anne Arens, Anne-Mette K. Hein, Uwe Appelt, Anika Joecker, Søren Mønsted, Bjarne Knudsen, Naomi Thomson, Richard Lussier, Cecilie Boysen, Roald Forsberg. Comparison of variant calling from whole exome and transcriptome sequencing using CLC Cancer Research Workbench. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5332. doi:10.1158/1538-7445.AM2014-5332
Abstract 5339: Deterministic in silico modeling predicts sensitivity of glioblastoma to targeted therapy
Authors: Pingle Sandeep C. , Pastorino Sandra , Muktharavam Rajesh , Jiang Pengfei , Chao Ying , Abbasi Taher , Vali Shireen , Kesari Santosh 
Published: May 2015

Abstract
Glioblastoma (GBM) is an aggressive disease associated with poor survival. The key to developing better diagnostic and therapeutic strategies is accounting for the complexity of GBM biology. This challenge of integrating vast genomic and proteomic data can be addressed by a comprehensive systems modeling approach. To this end, we employ an in silico modeling approach, wherein we utilize genomic and proteomic data to simulate tumor cells and predict drug responses. Using our in silico model, we replicated findings from a recent hypothesis-independent, empirical study that analyzed the sensitivity of hundreds of profiled cancer cell lines to 130 different anticancer agents. Among the drug-mutation associations reported in this study, our in silico model validated ∼85% of the associations. We also used the tumor model to predict sensitivity of patient-derived GBM lines to different targeted therapeutic agents. These analyses showed ∼75% agreement of in silico drug sensitivity with in vitro experimental findings. We aim to use this model to stratify patients for clinical trials. By accurately predicting responses of patient cancer cells to targeted agents a priori, the in silico tumor model provides an innovative approach to personalizing therapy for GBM and promises to improve clinical management of cancers.
Citation Format: Sandeep C. Pingle, Sandra Pastorino, Rajesh Muktharavam, Pengfei Jiang, Ying Chao, Taher Abbasi, Shireen Vali, Santosh Kesari. Deterministic in silico modeling predicts sensitivity of glioblastoma to targeted therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5339. doi:10.1158/1538-7445.AM2014-5339
Abstract 5343: Continuing expression of SHP2E76K is required to maintain lung tumors induced by the active SHP2E76K mutant in transgenic mice
Authors: Schneeberger Valentina E. , Luetteke Noreen , Ren Yuan , Foroutan Parastou , Martinez Gary V. , Haura Eric B. , Coppola Domenico , Wu Jie 
Published: May 2015

Abstract
The SHP2 protein tyrosine phosphatase is activated by growth factor receptor oncogenes or by gain-of-function (GOF) missense mutations such as SHP2E76K in human cancer. To study the oncogenic function of GOF SHP2 mutants and the dependency of SHP2 mutant-induced tumors, we established transgenic mice containing the tetO-SHP2E76K transgene. tetO-SHP2E76K mice were bred to CCSP-rtTA mice to direct expression of the transgene in type II pneumocytes to assess the role of the SHP2 mutant in lung adenocarcinoma. When the CCSP-rtTA/tetO-SHP2E76K bitransgenic mice were induced with doxycycline (dox), they developed papillary adenomas that progressed to adenocarcinoma in 6-9 months. This result demonstrates the oncogenic activity of the GOF SHP2 mutant in our mouse model of lung adenocarcinoma. Consistent with previous studies in cultured cells, lung tissues from dox-induced CCSP-rtTA/tetO-SHP2E76K have elevated pGab1, pErk, pSrc and c-Myc. Using magnetic resonance imaging (MRI), we were able to detect lung tumors in the dox-induced CCSP-rtTA/tetO-SHP2E76K bitransgenic mice. To determine if the SHP2E76K-induced lung tumors require continuing expression of the SHP2 mutant for tumor maintenance, dox was withdrawn from the CCSP-rtTA/tetO-SHP2E76K mice after detection of lung tumors by MRI. When these mice were examined again by MRI one month after dox withdrawal, the lung tumors were no longer detectable. Histological evaluation of lung tissues revealed residual hyperplastic lesions as well as evidence of necrosis, while biochemical analysis showed that pGab1, pErk, pSrc and Myc returned to basal levels. Thus, discontinuation of SHP2E76K expression resulted in tumor regression. These data indicate that continuing expression of SHP2E76K is required for maintenance of the SHP2 mutant-induced lung tumors.
Citation Format: Valentina E. Schneeberger, Noreen Luetteke, Yuan Ren, Parastou Foroutan, Gary V. Martinez, Eric B. Haura, Domenico Coppola, Jie Wu. Continuing expression of SHP2E76K is required to maintain lung tumors induced by the active SHP2E76K mutant in transgenic mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5343. doi:10.1158/1538-7445.AM2014-5343
Abstract 5378: Actions of nanoparticulate tetraiodothyroacetic acid (Nanotetrac) on human prostate carcinoma xenograft growth, vascularity and integrin response to radiation
Authors: Mousa Shaker A. , Thangirala Sudha , Yalcin Murat , Leith John T. , Hercbergs Aleck , Lin Hung-Yun , Tang Heng-Yuan , Luidens Mary K. , Davis Paul J. 
Published: May 2015

Abstract
Tetraiodothyroacetic acid (tetrac) covalently bound to a nanoparticle (poly[lactic-co-glycolic acid]) (= Nanotetrac) has anti-cancer and anti-angiogenic properties that are initiated exclusively at a cell surface receptor on integrin αvβ3 of cancer cells and dividing blood vessel cells. The anti-cancer activities are pro-apoptotic by multiple mechanisms, disorder gene expression in multiple cancer cell survival pathways and are radiosensitizing. The anti-angiogenic effects involve disruption of actions of VEGF, bFGF, PDGF and EGF. In the present studies, susceptibility of human prostate cancer cell xenografts to activity of Nanotetrac was determined in grafts in the nude mouse or to the chick chorioallentoic membrane (CAM) model and radiosensitivity was estimated in the CAM system. Androgen-sensitive LNCaP cell xenografts in the CAM exposed to Nanotetrac (1 μg/CAM) showed 40% decreases in tumor weight and vascular branch points and 50% reduction in hemoglobin content at 7 d (P &lt; 0.01). LNCaP xenograft volumes in the male mouse were reduced by 50% at 5 days (P &lt; 0.01), approximating the volume of the tumor cell implant. In vivo imaging system (IVIS) scans of orthotopic androgen-independent PC3 cell xenografts in the nude mouse showed substantial reduction in tumor size vs. control (PBS) at 7 d (50% reduction) and at 17 d (75% reduction) post-implantation. Radiation studies in PC3 cell tumors established in the CAM system demonstrated that within 1 h of exposure to 1-2 Gy radiation, there was apparently defensive activation (assumption of ‘open conformation’) of αvβ3. Receptor activation response to radiation was blocked by Nanotetrac. We have shown in other cancer cell lines that Nanotetrac inhibits repair of radiation-induced double-stranded DNA breaks and propose that, based on the current observations, this DNA repair effect is due to inhibition of radiation-caused activation of αvβ3. In summary, examined in two models and acting at the cell surface, Nanotetrac substantially reduces volume/weight and vascularity of human prostate cancer xenografts. The agent also inhibited activation of integrin αvβ3 that is induced by radiation exposure and is seen to be a component of the radioresistance response.
Citation Format: Shaker A. Mousa, Sudha Thangirala, Murat Yalcin, John T. Leith, Aleck Hercbergs, Hung-Yun Lin, Heng-Yuan Tang, Mary K. Luidens, Paul J. Davis. Actions of nanoparticulate tetraiodothyroacetic acid (Nanotetrac) on human prostate carcinoma xenograft growth, vascularity and integrin response to radiation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5378. doi:10.1158/1538-7445.AM2014-5378
Abstract 538: microRNAs as modifiers of stem cell properties in breast cancer: a whole genome approach
Authors: Bonetti Paola , Marzi Matteo J. , nicassio francesco 
Published: May 2015

Abstract
Cancer stem cells (CSCs) are cells with aberrantly regulated stem-like characteristics, such as self-renewal and quiescence. In breast cancer, CSCs have been shown to drive the tumorigenic process and to contribute to the emergence of therapeutic resistance and disease relapse. Based on this background, we decided to focus on the mechanisms that sustain CSC growth, namely self-renewal, to reveal molecules and pathways that control SC biology under physiological and pathological conditions.
Recent research suggests a key role for non-coding RNAs (microRNAs - miRNAs; and long non coding RNAs - lncRNAs) in the control of genetic program that specifies stem cell identity and properties. Nevertheless, we still do not know which non-coding RNAs are involved and how they influence self-renewal or differentiation properties of the normal as well the cancer SC pool in the breast tissue. Based on these premises we aimed at isolating those non-coding RNAs (either lncRNAs or miRNAs) that significantly associates with the self-renewal properties and the content of stem cells in the normal mammary gland and in human breast cancer to search for: i) “markers” that improve the stratification and prognosis of human breast cancer; and ii) “modifiers” (enhancing or suppressing) of self-renewal properties of breast normal and cancer stem cells.
In the long-term, our findings could serve as a basis to develop alternative strategies for the treatment of breast cancer that could radically improve the clinical management of breast cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Paola Bonetti, Matteo J. Marzi, francesco nicassio. microRNAs as modifiers of stem cell properties in breast cancer: a whole genome approach. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 538. doi:10.1158/1538-7445.AM2014-538
Abstract 5389: Discovery of small molecule inhibitors of the interaction between PPARγ and SMRT
Authors: Min Jaeki , Attia Ramy Naguib , Arnold Leggy A , Teske Kelly , Connelly Michele , Lemieux George , Ashrafi Kaveh , Shelat Anang , Guy R. Kiplin 
Published: May 2015

Abstract
The gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) is a ligand-activated nuclear hormone receptor that plays central roles in regulating adipogenesis and maintaining lipid and glucose homeostasis. PPARγ is the molecular target for the thiazolidinedione (TZD) class of antidiabetic drugs. While clinically efficacious, the TZDs exhibit significant side effects that are mechanistically linked to PPARγ including weight gain, edema, and heart failure. SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that are critical for normal PPARγ function and act by repressing PPARγ-mediated transcriptional activity in the absence of agonist ligands. In order to explore an alternate method of activating PPARγ signaling, we designed a biochemical assay for the purpose of high-throughput screening (HTS) to identify inhibitors of the interaction between PPARγ and corepressors from our in-house library compounds (292K), which might act as pharmacological agonists. Herein, we report the use of this method to discover small molecule inhibitors of the corepressor interaction with PPARγ. Following hit validation and evaluation, we identified small molecule inhibitors acting through this novel mechanism that potently induce a cellular response similar to the known PPARγ agonist rosiglitazone. In addition, we also confirmed that our hit compound revealed induced adipogenesis in 3T3-L1 cell and reduced fat storage in C.elegans model. These findings highlight the potential of targeting the interaction of PPARγ and SMRT for the discovery of small molecule agonists of PPARγ.
Citation Format: Jaeki Min, Ramy Naguib Attia, Leggy A Arnold, Kelly Teske, Michele Connelly, George Lemieux, Kaveh Ashrafi, Anang Shelat, R. Kiplin Guy. Discovery of small molecule inhibitors of the interaction between PPARγ and SMRT. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5389. doi:10.1158/1538-7445.AM2014-5389