bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 512: p16INK4A down-regulation activates breast stromal adipocytes.
Authors: Alkhalaf Huda H. , Aboussekhra Abdelilah 
Published: August 2014

Abstract
Obesity, a disease linked to increased number of adipocytes in various tissues, is now recognized as a risk factor for the development of breast cancer. Importantly, obesity has been reported to be associated with the occurrence of larger, more advanced tumors and aggressive cancer pathological features, including lymph node metastasis, advanced tumor stage, and high grade. Cancer-associated adipocytes (CAAs), the most abundant cellular component of breast cancer-associated stroma, promote carcinogenesis through paracrine effects. However, the molecular basis of adipocytes implication in breast carcinogenesis remains elusive. To shed light on this important phenomenon, we established and characterized normal adipocytes from post-plastic surgery of breast tissues. We have shown that these cells express various adipocyte biomarkers, including Leptin, TNF-α and FABP4. Furthermore, we investigated the role of the tumor suppressor p16 INK4A protein in adipocytes activation. We have found that specific down-regulation of p16INK4A by shRNA increased the expression/secretion levels of various adipokines including leptin, activated breast adipocyte and enhanced their migration/invasion abilities. Consequently, media conditioned with these cells stimulated the proliferation and the migration/invasion of breast cancer cells and enhanced endothelial cell differentiation into capillary-like structures. In addition, we have also shown that media conditioned with breast cancer cells decrease the expression of p16INK4A and increase the expression of leptin in adipocytes.
These results provide the first indication that p16INK4A down-regulation in breast stromal adipocytes is an important step toward their activation.
Citation Format: Huda H. Alkhalaf, Abdelilah Aboussekhra. p16INK4A down-regulation activates breast stromal adipocytes. [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 512. doi:10.1158/1538-7445.AM2013-512
Abstract 5123: In vitro culture for characterization of circulating GFP-expressing tumor cells in orthotopic lung cancer models .
Authors: Kološtová Katarína , Liberko Marián , Hroncová Eva , Hoffman Robert M. , Bobek Vladimír 
Published: August 2014

Abstract
In the present study circulating tumor cells (CTCs) were isolated from H460-RFP orthotopic human lung cancer model in mice. In vitro culture of CTCs has enabled us comparison of the chemosensitivity of tumor cells from primary H460 culture and of CTCs solated from blood grown in vitro. Cell line H460-RFP human lung cancer cells were grown to 70-80% confluence. Primary tumor were grown after subcutaneous injection of cultured cells. Fragments of tumor tissue (1 mm × 1 mm) were implanted into the lungs of nude mice. At 14 days, the mice were sacrificied and blood was taken by cardiac puncture for CTC-analysis. The blood (0.5 ml), obtained by cardiac puncture, was put into an EDTA tube (BD) and the CTC cells were enriched by immunomagnetic separation targeted to eptihelial antigens. The enriched fraction or whole blood was put into culture. Cell growth was then monitored by fluorescence microscopy. The isolation and culture of the fluorescent CTC will enable their further characterization.
Citation Format: Katarína Kološtová, Marián Liberko, Eva Hroncová, Robert M. Hoffman, Vladimír Bobek. In vitro culture for characterization of circulating GFP-expressing tumor cells in orthotopic lung cancer 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 5123. doi:10.1158/1538-7445.AM2013-5123
Abstract 5129: AGR2 is a potential marker for metastatic human oral squamous cell carcinoma.
Authors: Chen Yi-Ting , Ho Chung-Liang , Chen Po-Ku , Chen Yuh-Ling , Chang Chung-Fa 
Published: August 2014

Abstract
Purpose: The mortality of oral cancer, which is a common subtype of human and neck squamous cell carcinomas (HNSCC), is increasing in Taiwan, Southeast Asia, and eastern countries during the last twenty years. Averagely, the 5-year survival rate of distant metastasis of oral carcinoma is less than 30-40%. Prevention of cancer metastasis to distant organs is one of practical approaches that may reduce the mortality of patients. This study aims to identify novel metastatic tumor markers for oral cancer.
Experimental Design and Results: A high metastatic sub-population, HSC-3-5 cells, was divided from human oral cancer HSC-3 by Transwell invasion assay. Our results indicated that HSC-3-5 cells exhibited higher metastatic capacities due to re-arrangement cytoskeleton and subsequently epithelial mesenchymal transition transformation in vitro. In addition, metastatic and tumorigenetic capacities of HSC-3-5 cells were characterized by spontaneous and experimental metastasis experiments in vivo. The microarray-based gene expression profiles of HSC-3/HSC-3-5 cells and their corresponded xenografts (orthotropic and heterotopic) were then performed. Anterior gradient 2 (AGR2), a pro-oncogenic signaling intermediate in various human cancers, was the most significantly up-regulated gene in HSC-3-5 cells compared with HSC-3. Furthermore, overexpression of AGR2 protein was verified in cells, xenograft animal models, and clinical patient tissues, and it encompassed positive relation with OSCC metastasis.
Conclusions: A high metastatic sub-population HSC-3-5 cell line derived from human oral cancer HSC-3 cells was divided. HSC-3-5 cells represented higher capacities not only in metastasis but also in tumorigenesis. According to microarray gene profiles and immunohistochemistry analysis, the expression of identified potential biomarker, AGR2, showed positive relationship with tumor metastasis during oral carcinogenesis.
Citation Format: Yi-Ting Chen, Chung-Liang Ho, Po-Ku Chen, Yuh-Ling Chen, Chung-Fa Chang. AGR2 is a potential marker for metastatic human oral squamous cell carcinoma. [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 5129. doi:10.1158/1538-7445.AM2013-5129
Abstract 5143: From sequencing data to mutation spectra: a high throughput analysis pipeline.
Authors: Jones David , Butler Adam P. , Teague Jon W. , Raine Keiran M. , Menzies Andrew , Marshall John , Hinton Jonathan , Dronov Serge , Stebbings Lucy , Jayakumar Alagu , Leroy Catherine , Zamora Jorge , Ramakrishna Manasa , Papaemmanuil Elli , Davies Helen , Cooke Susanna L. , Nik-Zainal Serena , McDermott Ultan , Stratton Michael R. , Campbell Peter 
Published: August 2014

Abstract
Advances in massively parallel sequencing technology have revolutionized the way we characterise cancer genomes and provided significant new insights to our understanding of the mechanisms that underpin oncogenesis. A diverse range of mutations types including single base-pair changes, insertions, deletions, copy number alterations and larger structural variations are common in cancer genomes.
To rapidly and accurately screen next generation sequencing data for these somatic mutations in cancer, the Cancer Genome Project (CGP) has developed a high throughput analysis pipeline utilising a suite of analysis software developed by the group. Built around a compute farm of ∼2,000 nodes and using a Lustre filesystem, raw data files (BAM etc.), analysis results files and version information are efficiently stored and tracked in our archive/storage system, FileTrk. Lane data is aligned using Burrows-Wheeler Aligner (BWA) and web interfaces have been developed to allow scientific staff to rapidly QC aligned lanes. Once QC'd and desired coverage is reached, lanes are merged into a single sample BAM file and the sample is then ready for analysis.
In house algorithms are used to detect point mutations (CaVEMan), structural variation breakpoints (Brass) and copy number changes (ASCAT and PICNIC), whilst Pindel is used to detect small insertions/deletions. Post-processing filters then remove false positives and the results are uploaded into a database. Mutations are annotated to the protein and RNA levels using standard nomenclature (Vagrent, in-house software). Downstream analysis software has been developed (CANDI, in-house software) which produces a range of plots to aid visualisation of mutation context and mutation spectra patterns in related cancer samples.
Current IT development is focussed on converting the pipeline to produce and store VCF output, incorporate further downstream analysis software and automate data export to COSMIC and the ICGC data portal.
Citation Format: David Jones, Adam P. Butler, Jon W. Teague, Keiran M. Raine, Andrew Menzies, John Marshall, Jonathan Hinton, Serge Dronov, Lucy Stebbings, Alagu Jayakumar, Catherine Leroy, Jorge Zamora, Manasa Ramakrishna, Elli Papaemmanuil, Helen Davies, Susanna L. Cooke, Serena Nik-Zainal, Ultan McDermott, Michael R. Stratton, Peter Campbell. From sequencing data to mutation spectra: a high throughput analysis pipeline. [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 5143. doi:10.1158/1538-7445.AM2013-5143
Abstract 5147: drugCARD: a database of anticancer treatment regimens and drug combinations.
Authors: Fernandez Eric , Pang Jianxiong , Snell Chris , Derow Cathy , Brightman Frances , Chassagnole Christophe , Jackson Robert 
Published: August 2014

Abstract
Physiomics and Pharmacometrics have collaborated to design a new database of anti-cancer drugs and therapeutic treatment information. The objective is to provide a database of anti-neoplastic agents, regimens and combinations for use by clinicians and researchers in oncology.
The drugCARD database, accessible through the web, offers data on more than 130 anti-cancer drugs (small molecules and biologics) used in research and in the clinic. It contains information on drug combinations as well as several hundreds of cancer chemotherapy regimens used routinely in the clinic. The data are classified according to tumour type, species and experimental system (in vitro or in vivo). This database will be regularly expanded and curated with the most current information.
Individual drug information contained within the database comprises pharmacokinetic profiles, mechanisms of action and resistance, dose-response effect, dosing limits, therapeutic index and immunosuppression data. Drug combinations are also referenced. The database covers synergy or antagonism, and includes the combination therapeutic index and cross-resistance information. Drug combinations where the level of synergy is dependent upon the drug schedule, drug sequence or administration timing are also referenced and thoroughly discussed. The user can browse and compare chemotherapeutic regimens, and analyse the overall drug dose over a course of treatment, by tumour type, in animal and clinical models. Moreover, the database enables users to design new combinations and regimens that obey dosing constraints (such as MLD and MTD), and can be used to determine drug candidates that could be combined with a new chemical or biological entity, given the respective mechanisms of action and other PK/PD data. Data can be exported for analysis in spreadsheets, modelling software or simulation packages. Advanced functions will include the ability to carry out statistical analysis on drug usage and dosing in various contexts. Finally, the database allows the expression and nomenclature of chemotherapy regimens to be standardized, which is of paramount importance in improving efficacy, as well as reducing medication errors (Kohler et al 1998).
Citation Format: Eric Fernandez, Jianxiong Pang, Chris Snell, Cathy Derow, Frances Brightman, Christophe Chassagnole, Robert Jackson. drugCARD: a database of anticancer treatment regimens and drug combinations. [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 5147. doi:10.1158/1538-7445.AM2013-5147
Abstract 5148: CanDrA: Cancer-specific driver missense mutation annotation with optimized features.
Authors: Mao Yong , Chen Han , Liang Han , Meric-Bernstam Funda , Mills Gordon , Chen Ken 
Published: August 2014

Abstract
Driver mutations are somatic mutations that provide growth advantage to tumor cells, while passenger mutations are those that are not functionally associated with oncogenesis. Distinguishing drivers from passengers is challenging because drivers occur much less frequently than passengers, they turn to have low prevalence, and their functions are multifactorial. Missense mutations are excellent candidates for driver identification, as they occur more frequently and are potentially easier to target than other types of mutations. Although several methods have been developed for predicting the functional impact of missense mutations, only a few are specifically designed for identifying driver mutations. As more mutations are being discovered, more accurate predictive models can be developed using machine learning approaches that systematically characterize the commonality and peculiarity of somatic mutations under specific cancer background. Here, we present such a Cancer Driver Annotation (CanDrA) tool that assesses the driver potential of missense somatic mutations based on a set of 95 structural and evolutionary features computed by over 10 functional prediction algorithms from SNVBOX, VEP, ANNOVAR and Mutation Assessor. Through feature optimization and supervised training, CanDrA outperforms existing tools in analysing the glioblastoma multiforme and the ovarian carcinoma data in The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia project.
Citation Format: Yong Mao, Han Chen, Han Liang, Funda Meric-Bernstam, Gordon Mills, Ken Chen. CanDrA: Cancer-specific driver missense mutation annotation with optimized features. [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 5148. doi:10.1158/1538-7445.AM2013-5148
Abstract 5149: Translating biospecimen science research results to improved biospecimen practices.
Authors: Moore Helen M. , Engel Kelly , Greytak Sarah , Bass B. Paige , Vaught Jim 
Published: August 2014

Abstract
Cancer tissues and blood are collected, processed and stored in different ways, across the country and across the world. Biospecimen Science is the study of how different methods of biospecimen collection, processing, and storage affect downstream analysis. The NCI Biospecimen Research Network (BRN) program sponsors, conducts, and collaborates on Biospecimen Science research to better understand how biospecimen pre-analytical factors influence the molecular integrity of biospecimens, and in turn, how such variation affects the reproducibility of research results. New data on how pre-analytical variation affects molecular integrity will support best practice Standard Operating Procedures for research and clinical trials biospecimens.
This presentation will focus on results from the first phase of the BRN program and current efforts to translate research results to evidence-based biospecimen practices. A summary of research results will be presented from several research studies which have performed systematic perturbations of blood and tissue collection and processing procedures, with subsequent molecular analysis. We will also present an overview of the Biospecimen Research Database (BRD; https://brd.nci.nih.gov), developed to improve access to the literature in Biospecimen Science. The BRD is a free and publicly accessible web-based database that currently contains over 1500 review and research articles covering a broad range of topics spanning the biospecimen lifecycle. Articles are meticulously categorized and annotated by a team of Ph.D. level scientists according to the type of biospecimen and technology platform used, the experimental variables investigated, and many other parameters. Progress will be described on a new approach to perform meta-analyses of the literature evidence related to different tissue preservation methodologies, such as freezing and temperature storage methods and formalin fixation and paraffin embedding. In addition, we will describe current progress on the development of evidence-based biospecimen practices based on BRN research results, literature evidence, and expert input.
Citation Format: Helen M. Moore, Kelly Engel, Sarah Greytak, B. Paige Bass, Jim Vaught. Translating biospecimen science research results to improved biospecimen practices. [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 5149. doi:10.1158/1538-7445.AM2013-5149
Abstract 515: Aurora-A is a determinant of tamoxifen resistance by phosphorylation and activation of ERα in breast cancer.
Authors: Zheng Xiangqian , Guo Jianping , Yang Hua , He Lili , Kanai Masayuki , Coppola Domenico , Gao Ming , Ren Xiubao , Cheng Jin Q. 
Published: August 2014

Abstract
Aurora-A kinase is frequently overexpressed/activated in various types of human malignancy including breast cancer. In this study, we demonstrated that Aurora-A induces estrogen receptor α (ERα) transactivation activity in the presence and absence of estrogen. Aurora-A also interacts with and phosphorylates ERα at serine-167 and -305 in vitro and in vivo. As a result, Aurora-A induces ERα transcriptional activity, enhances ERα binding to DNA and transcriptionally up-regulates its targeting genes such as CCDN1 in a phospho-ERα-Ser-167/305 dependent manners. Further, overexpression of Aurora-A decreases whereas depletion of Aurora-A enhances tamoxifen sensitivity in ERα-positive breast cancer cells. Significantly, Aurora-A inhibitor synergized with tamoxifen and overcame tamoxifen-resistance in vitro and in animal model. These data suggest that ERα is a bona fide substrate of Aurora-A and that Aurora-A plays a pivotal role in tamoxifen resistance. Thus, Aurora-A represents a critical therapeutic target in breast cancer endocrine-therapy.
Citation Format: Xiangqian Zheng, Jianping Guo, Hua Yang, Lili He, Masayuki Kanai, Domenico Coppola, Ming Gao, Xiubao Ren, Jin Q. Cheng. Aurora-A is a determinant of tamoxifen resistance by phosphorylation and activation of ERα in breast 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 515. doi:10.1158/1538-7445.AM2013-515
Abstract 5153: PAK2-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation.
Authors: Li Tingting , Zhang Jishuai , Zhu Feng , Wen Weihong , Zykova Tatyana , Li Xiang , Liu Kangdong , Peng Cong , Ma Wei-Ya , Dong Zigang , Bode Ann M. 
Published: August 2014

Abstract
PAK2 plays an important role in cell proliferation, but the direct downstream proteins and precise regulatory mechanism involved in mediating PAK2’s role in proliferation are not yet clear. Here, we found that epidermal growth factor (EGF) induces phosphorylation of c-Jun by P21-activated kinase (PAK2). Knockdown of PAK2 in JB6 Cl41 (P+) cells had no effect on c-Jun phosphorylation at Ser63 or Ser73 but resulted in decreases in EGF-induced anchorage-independent cell transformation, proliferation and AP-1 activity. The oncoprotein c-Jun is one of the components of the activator protein-1 (AP-1) transcription factor complex. AP-1 activates a variety of tumor-related genes and promotes tumorigenesis and malignant transformation. Knockdown of PAK2 in SK-MEL-5 melanoma cells also decreased colony formation, proliferation and AP-1 activity. We found that PAK2 binds and phosphorylates c-Jun at five threonine sides (Thr2, Thr8, Thr89, Thr93 and Thr286) in vitro and in vivo. Mutation at all five sites decreased the transforming ability of JB6 cells. These results indicated that PAK2/c-Jun signaling plays an important role in tumorigenesis and provides an increased understanding of the signaling transduction mechanism of skin tumor cells and suggests that PAK2 might be a new chemopreventive or chemotherapeutic target.
Citation Format: Tingting Li, Jishuai Zhang, Feng Zhu, Weihong Wen, Tatyana Zykova, Xiang Li, Kangdong Liu, Cong Peng, Wei-Ya Ma, Zigang Dong, Ann M. Bode. PAK2-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. [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 5153. doi:10.1158/1538-7445.AM2013-5153