bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 298: Tumor-associated lymphatic vessels: Hijacking mechanisms of peripheral tolerance
Authors: Swartz Melody A. , Lund Amanda W. , Shields Jacqueline D. , Kourtis Iraklis C. , Hirosue Sachiko 
Published: August 2012

Abstract
Lymphatic vessels drain fluid, antigens, and immune cells from the periphery to the lymph nodes (LNs). In addition to transporting activated dendritic cells to mount adaptive immune responses in the LN, lymphatic drainage is brings soluble antigens from the periphery to LN-resident immature dendritic cells and B cells. It is also the most common site for cancer metastasis. Despite its importance, the role of tumor-associated lymphatic vessels and their drainage to the LN in regulating host immune responses to the tumor is poorly understood. We show that tumor expression of VEGF-C, the most potent lymphatic growth factor, promotes pro-tumor immune tolerance by several mechanisms. For one, it enhances drainage to the draining LN, where tumor antigens along with suppressive cytokines bathe the LN and could affect B and T cell education there. Second, tumor VEGF-C upregulates CCL21 in the tumor stroma and surrounding lymphatic vessels, which itself promotes T cell infiltration and suppression. Third, VEGF-C drives peritumoral and LN lymphangiogenesis, which can modulate the myeloid cell repertoire towards more suppressive phenotypes. These changes resulted in increased infiltrations of regulatory T cells and myeloid-derived suppressor cells, and increased levels of regulatory cytokines. Interestingly, VEGF-C-expressing tumors were impervious to prior immunization against tumor antigen, unlike control-transfected tumors, which were hindered by the vaccine-induced immune response. Together, these findings suggest that lymphatic drainage serves to maintain peripheral tolerance and that tumors may hijack such mechanisms to escape host immunity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 298. doi:1538-7445.AM2012-298
Abstract 2980: An integrated cross-species transcriptional network analysis of metastatic susceptibility
Authors: Hu Ying , Wu Gang , Rusch Michael , Lukes Luanne , Buetow Kenneth H. , Zhang Jinghui , Hunter Kent W. 
Published: August 2012

Abstract
Metastatic disease is the proximal cause of mortality for most cancers and remains a significant problem for the clinical management of neoplastic disease. Recent advances in global transcriptional analysis have enabled better prediction of individuals likely to progress to metastatic disease. However, minimal overlap between predictive signatures has precluded easy identification of key biological processes contributing to the pro-metastatic transcriptional state. To overcome this limitation, we have applied network analysis to two independent human breast cancer data sets and three different mouse populations developed for quantitative analysis of metastasis. Analysis of these data sets revealed that the gene membership of the networks is highly conserved within and between species, and that these networks predicted distant metastasis free survival. Furthermore these results suggest that inherited susceptibility to metastatic disease is cell autonomous in ER+ tumors and associated with the mitotic spindle checkpoint. In contrast, susceptibility to metastasis is tumor non-autonomous in ER- patients and associated with an inherited difference in immune infiltration of the primary tumor. These results suggest that the application of network analysis across species may provide a robust method to identify key biological programs associated with human cancer progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2980. doi:1538-7445.AM2012-2980
Abstract 2987: Regulatory network discovery using 3-way integration of high-dimensional mRNA, miRNA and lncRNA expression data from the entire NCI60 cancer cell line panel
Authors: Mestdagh Pieter , Hellemans Jan , D'haene Barbara , Derveaux Stefaan , Wong Kee , Kotturi Paul , Ginzinger David , Vandesompele Jo 
Published: August 2012

Abstract
With the discovery of different non-coding RNA species, the complexity of the transcriptome and its regulation has increased dramatically. Next to the well-studied small non-coding miRNAs, several thousands of long non-coding RNAs (lncRNAs) have recently been described. Like miRNAs, lncRNAs appear to predominantly function as regulators of gene expression and are implicated in various regulatory networks involving both miRNAs and protein-coding genes. In order to facilitate the search for miRNA-lncRNA-mRNA regulatory networks in cancer we have profiled the expression of each of these RNA information layers using the high-throughput SmartChip RT-qPCR technology on the entire NCI60 cancer cell line panel. In total, three SmartChip Panels with 1050 miRNAs, 1250 cancer-focused mRNAs, and 1718 lncRNAs, respectively, were quantified with a minimum of 3 technical replicates against each cell line. Here, we present the results of an unprecedented integrated analysis aimed at identifying networks of highly co-regulated miRNA-lncRNA-mRNA clusters. In brief, individual clusters are annotated using a pathway enrichment approach whereby network edges are evaluated using miRNA target, lncRNA target, and transcription factor target predictions. MiRNA-lncRNA-mRNA clusters centered around key cancer genes are annotated and the complex interplay is described. This unique and extensive high quality dataset, comprised of three major information layers of the NCI60 cell line transcriptome offers numerous opportunities towards a better understanding of complex regulatory networks in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2987. doi:1538-7445.AM2012-2987
Abstract 2988: Exploring the association between immune-related genetic variations and virally mediated head and neck cancer
Authors: Levovitz Chaya , Posner Marshall , McKay James , Boffetta Paolo , Sikora Andrew 
Published: August 2012

Abstract
OBJECTIVES: Human papilloma virus (HPV)-related cancer of the oropharynx (tonsil and tongue base) makes up an increasing proportion of head and neck cancers. This raises the possibility that the host immune response may modulate susceptibility to HPV-related head and neck cancer. The overall goal of this project is to identify candidate immune-related genes associated with an increased risk of developing virally-mediated head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Data from a two-phased Genome Wide Association Study (GWAS) performed by the International Head and Neck Cancer Epidemiology Consortium (INHANCE) was evaluated for associations between genetic variants in candidate immune related genes and the risk of developing HNSCC. METHODS: We analyzed the GWAS dataset using a hypothesis-driven multi-candidate gene approach which incorporates improved methods for data quality control and candidate gene prioritization. This involved performing an association analysis using multi-variate logistic regression with over 300,000 SNPs. The candidate gene list, including over 900 immune-related genes, was developed using the Gene Ontology (GO) database and prioritized by both the GO priority score and a novel literature based ranking schema. Separate association analyses were performed on all samples and then on samples from patients with oropharyngeal cancer only. RESULTS: After adjusting for multiple testing, 15 of the immune related candidate genes had p values that reached significance in the association study performed on oropharyngeal samples including CBFA2T3, MAPKAPK2, ZAP70, CRTAM, PBX1, MAPK10, CD80, IL10, SOCS5, TGFBR1, EBF1, IGF1R, LYN, ITGAV. Mutations in many of these genes have previously been implicated in cancer risk, viral host-response, or epithelial immunity. CONCLUSIONS: Our analysis suggests that the immune system may modulate risk of developing virally-mediated HNSCC. Genes identified in this study may provide biomarkers for patient or population risk assessments that can potentially be used in implementing behavioral interventions, HPV vaccination, and other preventative strategies. Validation of immune-related genes associated with HNSCC susceptibility may provide clues to pathogenic mechanisms driving the acquisition of virally-related HNSCC. This abstract has been submitted on behalf of ARCAGE and the CE UADT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2988. doi:1538-7445.AM2012-2988
Abstract 2993: Comparison of copy number variation using exome sequencing and affymetrix SNP6.0 genotype array in human cancer cell lines
Authors: Wang Jian , Doman Thompson N. , Ma Xiwen , Li Dan S. , Aggarwal Amit , Yue Yong G. , Higgs Richard E. , Barber Thomas D. 
Published: August 2012

Abstract
Whole exome sequencing has been used successfully as a cost effective and unbiased method in the detection of single nucleotide variants (SNVs) in the coding regions of the human genome. Its application in identifying another class of genetic variability - copy number variation (CNV) - has been hindered by numerous factors including inconsistent exome capture probe specificity and efficiency for the target regions, discontinuous targets, and variable exon lengths etc. In the current work, we applied ExomeCNV, a depth-of-coverage based statistical analysis method developed by Sathirapongsauti et. al., to exome NGS data from a larger collection of cancer cell lines. The exomes were captured using Agilent SureSelect Human All Exon Kit and sequenced on the average depth of 70x using the Illumina HiSeq platform. To control for sequence coverage biases introduced by the capture technology, CNVs for each cancer cell line are presented as a ratio to a baseline control constructed using pooled samples processed in the same manner. Genotyping arrays are standard methods of choice for CNV discovery in cancer cell lines from the Cancer Genome Project by the Sanger Institute and the Cancer Cell Line Encyclopedia project by the Broad Institute. We obtained Affymetrix SNP6.0 genotype data for the cancer cell lines from these two sources. CNVs detected from exome sequencing were compared with those discovered from genotyping arrays in the same set of cancer cell lines. We present here a comprehensive comparison of the cancer cell line gene copy number determination from exome sequencing and genotyping methods. Our results indicate that, with sufficient exome coverage and properly constructed controls, copy number detection using exome data is a valuable alternative to genotype based approach.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2993. doi:1538-7445.AM2012-2993
Abstract 2998: BRG1 (SMARCA4) protein loss has profound effects on the transcriptome of non-small cell lung cancer (NSCLC) cell lines
Authors: Zhang Wei , Yao Yibing , Yan Jingsheng , Zhang Yu-An , Rios Jonathan , Girard Luc , Pertsemlidis Alexander , Wakeland Ward , Xie Yang , Solis Luisa M. , Wistuba Ignacio I. , Hanash Samir M. , Minna John D. , Gazdar Adi F. 
Published: August 2012

Abstract
Purpose: To study the gene expression profile of NSCLC cell lines with BRG1 protein loss. Background: BRG1 is the major catalytic subunit of the SWI/SNF chromatin remodeling complex and provides ATPase activity necessary for transcriptional regulation of multiple cellular pathways. BRG1 is frequently inactivated in lung cancers and loss of BRG1 is correlated with poor prognosis. Methods: Sixty eight NSCLC cell lines were analyzed. BRG1 protein was detected by western blotting using nuclear extracts. SMARCA4 deletions or mutations were identified by NextGen sequencing and/or Sanger sequencing using genomic DNA or cDNA. Published reports and SNP analysis were also used to verify our results. Gene expression profiles were determined by Illumina human WG-6 V3 beadchip. Microarray expression data was analyzed by Significance Analysis of Microarray (SAM) and Hierarchical clustering analysis. Results: Twenty five NSCLC cell lines had lost BRG1 protein expression. Sequencing analysis found homozygous mutations (deletions, nonsense, splicing site) in twenty two of the lines. Among forty three NSCLC cell lines with BRG1 protein expression, five had homozygous missense mutations, four had heterozygous mutations. Gene expression profiling demonstrated that nearly 1500 transcripts were differentially up or down regulated (false discovery rate &lt;5%) among the cell lines without BRG1 protein compared to the ones with WT BRG1. These transcripts are involved in many important cellular functions including proliferation, adhesion, epithelial-mesenchymal transition, signaling pathway, steroid receptor and oncogene expression. Hierarchical clustering analysis using these transcripts distinguished NSCLC cell lines without BRG1 protein as a group, different from other NSCLC cells as well as immortalized respiratory epithelial cells, while NSCLC cell lines with BRG1 missense mutations showed heterogeneity of expression patterns. Conclusions: BRG1 protein loss is frequent in lung cancer cells and has a distinct signature and profound effects on the transcriptome of NSCLC cell lines. Our findings support the concept that BRG1 functions as a “master regulator of master regulators.”
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2998. doi:1538-7445.AM2012-2998
Abstract 3: HER2 gene-amplified human breast cancer cells harboring a gatekeeper T768M mutation in HER2 overexpress EGFR ligands and are sensitive to dual therapeutic blockade of EGFR and HER2
Authors: Ghosh Ritwik , Narasanna Archana , Chakrabarty Anindita , Engelman Jeffrey A. , Arteaga Carlos L. 
Published: August 2012

Abstract
Intrinsic or acquired mutations in receptor tyrosine kinases (RTKs) can confer resistance to RTK-targeted therapies. A previous study reported that a ‘gatekeeper’ T768M mutation in HER2 confers resistance to the tyrosine kinase inhibitor (TKI) lapatinib. We generated BT474 cells stably expressing either T768M HER2 or GFP. Treatment with lapatinib disrupted HER3-p85 complex and blocked phosphorylation of HER2, HER3, AKT and Erk1/2 in BT474-GFP but not in BT474-T768M cells. BT474-T768M cells were also resistant to other anti-HER2 therapies such as trastuzumab. BT474-T768M cells were sensitive to the PI3K inhibitor BKM120 but not the MEK inhibitor CI1040, suggesting they still depend on the PI3K pathway for survival. Treatment with the irreversible HER2/EGFR inhibitor BIBW2992 (afatinib) eliminated P-HER2 and inhibited growth of cells expressing the mutant, suggesting they still depend on the ErbB receptor network to activate PI3K. Indeed, like in BT474-GFP (control) cells, BIBW2992 disrupted the association of p85 (PI3K) with HER3 and blocked phosphorylation of AKT. A co-culture experiment with varying proportions of BT474-GFP and BT474-T768M cells revealed that lapatinib-resistant acini emerge when as low as 5% of the population has T768M HER2. Moreover, we found that only 3.2% of the HER2 alleles had the T768M mutation in the BT474-T768M cells. This result suggests that allelic dilution will render it difficult to identify this drug resistant mutation with conventional sequencing techniques (i.e., Sanger) in patients with HER2 gene-amplified breast cancer. Next, we stably expressed either wild-type or T768M HER2 in MCF10A cells. Both WT and T768M HER2 resulted in increased phosphorylation of HER3 and AKT. MCF10A-HER2 but not MCF10A-T768M cells were sensitive to growth inhibition by lapatinib. Lapatinib blocked HER2, HER3 and tyrosine phoshorylation in MCF10A-HER2 but not in MCF10A-T768M cells. Quantitative PCR indicated that the BT474-T768M cells produce more EGFR ligands (EGF, TGFα, amphiregulin and HB-EGF) compared to BT474-GFP cells. Treatment with cetuximab, an EGFR antibody that blocks ligand binding, restored sensitivity of BT474-T768M cells to trastuzumab. Further, the BT474-T768M cells were sensitive to a combination of trastuzumab and lapatinib both in vitro and in vivo. Hence, dual blockade of HER2 and EGFR might be effective at trumping the development of HER2-overexpressing cancers bearing a gatekeeper mutation in T768M.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3. doi:1538-7445.AM2012-3
Abstract 300: Blockage of OPN induction via HGF/cMET signaling in multiple myeloma cells suppresses both MMP9 expression and RUNX2 expression of BMSCs associating with bone erosion of MM patients
Authors: Jung Woo June , Ahn Kwang-Sung , Ryu JIyeon , Park Soyoung , Park Juwon , Lee Chansu , Bae Eunkyung , Yoon Sung-Soo 
Published: August 2012

Abstract
Dynamic interaction between multiple myeloma cells (MM) and bone marrow stromal cells plays critical roles in progression of MM. Hepatocyte growth factor (HGF), one of these factors, as a c-Met ligand, activates mitogenic activation protein kinase (MAPK). OPN binds with integrins and CD44 variants and activates cell signaling involved in invasiveness, angiogenesis and bone remodeling. Increasing lines of evidence provide that HGF and OPN, respectively, associate with the progression of MM. However, the role of HGF in MM largely remains unknown. In bone marrow serum of MM patients, HGF expression correlated with OPN expression (p=0,0095), suggesting that HGF derived from bone marrow stromal cells stimulates OPN expression in MM cells. Firstly, we found that expression levels of OPN in HFG-treated MM cells (fraction of CD138+ cells) obtained from MM patients was higher than either HFG-treated bone marrow stromal cells or HFG-treated MM cells (fraction of CD138- cells). Also, induction of DKK1 by HGF, suggesting the inhibition of osteogenesis, was found in U266 cells and RPMI8226, Both HGF-mediated MAPK and PI3K/AKT results in activating NF-kB and increasing OPN expression and DKK1. Those expressions were effectively down-regulated in U266 cells transfected with shRNA c-MET. RUNX2 mRNA and MMP-9 mRNA was increased in bone marrow stromal cells (BMSCs) treated with OPN. In addition, combined cMET inhibitor and PI3K inhibitor effectively inhibited the RUNX2 and the MMP9 mRNA expression in both OPN alone treatment and co-treatment with OPN and HGF in BMSCs. Taken together, since Induction of OPN and DKK1 by HGF in MM cells could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs, blockage of HGF/cMET signaling leading to increasing levels of OPN and DKK1 may help to prevent from progressing bone erosion of MM patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 300. doi:1538-7445.AM2012-300
Abstract 3002: Identification of frequently altered protein networks in ependymomas
Authors: Bischof Jared M. , Scholtens Denise , Arndt Kelly , Wang Min , Wang Deli , Huang Chiang-Ching , Bonaldo Maria de Fatima , Gilbertson Richard J. , Soares Marcelo Bento 
Published: August 2012

Abstract
Ependymomas are glial tumors that originate from the walls of the cerebral ventricles or from the spinal canal. The five-year survival for intracranial ependymomas in children is approximately 65%. Ependymomas exhibit a wide range of DNA copy number alterations that vary greatly in size and location. We hypothesize that an underlying protein network exists that is consistently compromised by such DNA copy number alterations in ependymomas. In this study, we analyzed an array-comparative genomic hybridization dataset generated by Johnson and colleagues [Nature 466(7306):632-6, 2010] to determine whether a protein interaction network could be identified that might be consistently functionally compromised in pediatric ependymomas. This cohort of 203 primary ependymomas consisted of 106 posterior fossa, 56 supratentorial, and 41 spinal ependymomas. The genes within each altered region were used to perform network analyses with GeneGo and Ingenuity to uncover protein networks that were altered in a significant number of tumors. For calculation of statistical significance, 100,000 samplings of randomly selected regions - equal in gene number to the regions of gain or loss - were performed. Indeed, some protein networks were found to be over-represented in the structural alterations exhibited by this cohort (p&lt;0.05). These results warrant future investigations to demonstrate the role of the identified networks in the development and progression of ependymomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3002. doi:1538-7445.AM2012-3002
Abstract 3006: A systematical view on key genetic factors affecting somatic copy number alternations in different cancers
Authors: Li Yudong , Yuan Yuan , Liang Han 
Published: August 2012

Abstract
Along with somatic mutations and translocations, somatic copy number alternations (SCNAs) play essential roles in the development of cancers. However, it remains poorly understood what mutagenic features driving cancer SCNAs are encoded in the genome sequence and how their effects vary across different cancer types. Taking advantage of recently available the Cancer Genome Atlas (TCGA) data, we performed a systematic analysis on the effects of various genetic sequence features on cancer SCNAs. We first assessed the correlations of breakpoint density across different cancer types and found that they overall showed very strong positive correlations, but in some cases, the correlations varied from chromosome to chromosome. Next, we investigated the dependence of SCNAs on 16 sequence features and found that compared to copy number variations in human populations, SCNAs showed much weaker correlations, suggesting a stronger effect of functional selection on their observed patterns. Finally, we built integrative models to identify key features affecting different cancer SCNAs. Our study provides a systematic view how genome-wide sequence features affect cancer SCNAs and lays a foundation for identifying key SCNAs driving cancer pathogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3006. doi:1538-7445.AM2012-3006