bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-133: Genome-wide differences in DNA methylation between tumor and normal adjacent tissue mapped by high-throughput sequencing of methyl-CPG binding domain based affinity-purified genomic fragments
Authors: Meredith Gavin D. , Dudas Miroslav , Krissinger Daniel , Marnellos George , Adams Christopher 
Published: February 2011

Abstract
Aberrant DNA methylation is characteristic of many cancers and differences in methylation have been observed in a wide variety of genomic contexts; for example, both within “classic” promoter-associated CpG islands and also in distal, non-CpG island regions. Establishing a method to broadly and efficiently survey the methylation patterns genome-wide in matched tumor and normal genomic DNA and to elucidate differences in these “methylomes” is the objective of the work presented. The method combines the power of methyl-CpG binding domain (MBD) proteins to sensitively and selectively bind methylated DNA sequences with the coverage, precision, and accuracy provided by high-throughput sequencing. Notably, MBD-affinity capture can also be used to sub-fractionate genomic DNA based on its average methyl-CpG content. In parallel, patient-derived matched samples of fragmented genomic DNA from a breast tumor and normal adjacent tissue were enriched and fractionated based on their methyl-CpG content with a commercial MBD-based affinity reagent (see figure) and high-throughput sequencing libraries were prepared from each fraction. The libraries were sequenced at 50 bp read-length on a SOLiD 3 Plus system and mapped to the human reference genome. Peak analysis of the distribution of mapped reads permitted the discovery of hundreds of putative differentially methylation regions (DMRs). Differential methylation at a number of these positions was confirmed by bisulfite-sequencing. We conclude that such enrichment and fractionation, when coupled to high-throughput sequencing, can be used to efficiently survey the majority of DNA methylation marks within samples of genomic DNA and to discover genomic loci of differential methylation. We conclude that such enrichment and fractionation, when coupled to high-throughput sequencing, can be used to efficiently survey a large fraction of all DMRs between samples of genomic DNA and to discover genomic loci of differential methylation. These datasets can then be compared with ChIP-seq and/or RNA-seq data sets to begin to decipher the functional genomics and epigenomics of cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-133.
Abstract LB-14: Endogenous expression of oncogenic PI3K mutation leads to accumulation of pro- and antiapoptotic proteins at mitochondria
Authors: Buron Nelly , Porceddu Mathieu , Torrance Chris , Disley Darrin , Borgne-Sanchez Annie 
Published: February 2011

Abstract
The phosphatidylinositol 3-kinase subunit PI3K is frequently mutated in human cancers and therefore represents an interesting therapeutic target. Cancer resistance to therapies is often related to expression of anti-apoptotic Bcl-2 family members which negatively regulate mitochondrial cell death. We investigated the influence of PI3K mutations on Bcl-2 family proteins both at the cellular and mitochondrial level. We used human breast epithelial cell lines with an endogenous “knock-in” PI3K mutation (HME-1 cells harbouring the H1047R activating mutation) from which we purified the mitochondria to homogeneity (95%). We first characterized these mitochondria for their sensitivity to reference compounds (Calcium, t-Bid) on 3 parameters: swelling, m loss and cytochrome c release. Mitochondrial preparations from wild-type and mutated HME-1 were analysed for their protein pattern in Bcl-2 family members. We observed accumulation of anti-apoptotic (Bcl-xl and Bcl-2) and pro-apoptotic (Bad) proteins in mitochondria isolated from PI3K mutated cells. We showed that the excess of anti-apoptotic proteins at the mitochondria does not change their sensitivity to the Bcl-2 family inhibitor, ABT-737. Investigations with PI3K-inhibitors are currently undergoing to determine the mitochondrial on-target biomarker for drug development.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-14.
Abstract LB-140: An innovative approach for profiling of histone modification marks and gene expression across a panel of oncogenes and tumor suppressor genes in multiple cancer cell lines
Authors: Huang Jiaqiang , Quellhorst George J. , Gu Xiujing , Xiang Yan , Zeng Xiao , Boon Kathy 
Published: February 2011

Abstract
Objectives: Histone modification marks and gene expression profiling on multiple human oncogenes and tumor suppressor genes to study the correlation between epigenetic modifications and gene expression in cancer cells derived from different tissue/cell types.
Methodology: Chromatin Immunoprecipitation (ChIP) was performed on the isolated chromatin samples from various cancer cell lines (MCF7, A549, HepG2, HCT116, PC3 and HeLa) using antibodies against H3K4me2, H3K4me3, H3Ac, H3K27me3, H3K9me3, H4K20me3, and RNA Pol II. Each resulting ChIP DNA fraction was analyzed with a ChIP Real-Time PCR Array consisting of specific PCR primers targeting the downstream region of the transcription start site (within + 1Kb). For this study 84 oncogenes & tumor suppressor genes were measured simultaneously along with control gene regions characteristic for each histone modification. Real-time RT-PCR Arrays were also employed to analyze the mRNA levels for all 84 genes in the same 6 cancer cell lines. These results allow analysis to correlate specific histone marks with the transcript levels.
Results: The data indicate a much more complex correlation between modified histone marks and gene expression across different cancer cell lines. The results provide insights into the complex epigenetic regulation in cancer cells. The combination of ChIP-qPCR Arrays (histone modifications) and RT-qPCR Arrays to study multiple oncogenes and tumor suppressor genes simultaneously in various cancer samples should prove a valuable and fast approach in the assessment of the correlation between epigenetic regulation and clinical characteristics.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-140.
Abstract LB-151: Targeted gene resequencing in a K-ras-dependent mouse model of metastatic lung adenocarcinoma
Authors: McFadden David G. , Xuan Zhenyu , Rosebrock Adam , Politi Katerina , Santiago Philip , Hodges Emily , Winslow Monte , Hiramatsu Nobuhito , Pirun Mono , Crowley Denise , Bronson Roderick , Socci Nicholas , Varmus Harold , Hannon Greg , Jacks Tyler 
Published: February 2011

Abstract
Progression of lung adenocarcinoma to invasive, metastatic disease is responsible for the majority of deaths from lung cancer and remains incompletely understood. We have developed a genetically-engineered mouse model of lung adenocarcinoma initiated by mutant K-ras and loss of p53 that develops invasive, metastatic disease. In order to identify the genes and pathways that cooperate with oncogenic K-ras and loss of p53 to contribute to tumor development, progression, and metastasis, we have utilized in situ exon capture and massively parallel DNA sequencing to identify somatically-acquired point mutations in advanced stage murine lung adenocarcinoma cell lines. We have initially chosen a target set of 1283 cancer-relevant genes to develop our capture, sequencing, and bioinformatics platforms. Using tumor cell lines derived from K-ras-dependent tumors, we have successfully developed and refined these methods and have identified somatic mutations in our test samples. These mutations have been validated by conventional methods in the tumor cell line and founder tumor DNA. We have developed a production phase target gene set consisting of 1909 cancer-relevant genes and have initiated capture and sequencing of additional murine lung adenocarcinoma cell lines and tumors. We believe these datasets will expand the understanding of the biology of tumor progression and serve as an important biological filter for human cancer gene re-sequencing efforts.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-151.
Abstract LB-157: A murine model of Fanconi anemia-associated head and neck cancer
Authors: Hays Laura E. , Bagby Grover C. 
Published: February 2011

Abstract
Fanconi anemia (FA) predisposes patients to aggressive head-and-neck-squamous-cell-carcinomas (HNSCCs) early in life. These tumors are particularly difficult to treat because of the underlying hypersensitivity of all somatic cells from these patients to cross-linking agents. An in vivo model is thus badly needed to delineate the unique molecular mechanisms involved in tumor formation and to identify opportunities to exploit this mechanism therapeutically. Although mice with inactivating mutations of FA genes have been developed, these mice do not spontaneously develop HNSCCs. Therefore, we sought to develop our own model by treating wild-type (WT) and Fancc-deficient (FA-C) mice with the carcinogen 4-nitroquinoline 1-oxide for 45 weeks. Although tumor incidence, histological type and grade, and anatomical location were similar in WT and FA-C mice, cells isolated from FA-C tumors displayed higher levels of endogenous chromosomal instability compared to cells from WT tumors. None of the mice developed metastases, most likely because they required early euthanasia as tumor formation inhibited the ability to eat and drink. To compare the metastatic potential of WT and FA-C HNSCC cells, we subcutaneously injected these cells lines into the flanks of immunocompetent (C57Bl/6J) and immunodeficient (NOD/SCID) mice. Interestingly, tumors only formed in NOD/SCID mice indicating immune-mediated suppression of tumor growth in the immunocompetent mice. In NOD/SCID mice, 4 out of 6 WT and 3 out of 4 FA-C cell lines induced tumor formation. However, all of the tumor-forming FA-C lines produced aggressive tumors that penetrated into the retro-peritoneal space and/or produced hind-leg paralysis, while only 1 out of 4 WT lines invaded to this extent (a phenomenon that occurred in fewer than 25% of mice injected with this line). In addition, we found that tumor forming ability of FA-C HNSCC cell lines did not require loss of Fancc because FA-C lines transduced with wild-type Fancc remained fully tumorigenic in vivo. In conclusion, we have developed a model of FA related HNSCCs utilizing FA and WT cell lines. The model permits the outgrowth of tumors that are histologically, genomically, and biologically similar to corresponding tumors in humans. Currently we are utilizing this model to test the efficacy of small molecules in inhibiting FA tumor progression and are testing the role of the tumor microenvironment and the immune system in modulating the development of FA-related HNSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-157.
Abstract LB-17: WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ
Authors: Chan Siew Wee , Lim Chun Jye , Huang Caixia , Chong Yaan Fun , Harvey Kieran , Hong Wanjin 
Published: February 2011

Abstract
The transcriptional co-activators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. YAP and TAZ both possess WW domains which are important protein-protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY. The WW domains of YAP play complex regulatory roles as exemplified by two recent reports showing that they can positively or negatively influence YAP activity in a cell and context-specific fashion. In this study, we show that the WW domain of TAZ is important for it to transform both MCF10A and NIH3T3 cells and to activate transcription of ITGB2 but not CTGF, as introducing point mutations into the WW domain of TAZ (WWm) abolished its transforming and transcription-promoting ability. Using a proteomic approach we discovered potential regulatory proteins that interact with TAZ WW domain and identified Wbp2. The interaction of Wbp2 with TAZ is dependent on the WW domain of TAZ and the PPXY-containing C-terminal region of Wbp2. Knockdown of endogenous Wbp2 suppresses, whereas overexpression of Wbp2 enhances, TAZ-driven transformation. Forced interaction of WWm with Wbp2 by direct C-terminal fusion of full-length Wbp2 or its TAZ-interacting C-terminal domain restored the transforming and transcription-promoting ability of TAZ. These results suggest that the WW domain-mediated interaction with Wbp2 promotes the transforming ability of TAZ.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-17.
Abstract LB-173: Statin use and colorectal adenoma risk: Results from the Adenoma Prevention with Celecoxib (APC) trial
Authors: Bertagnolli Monica Marie , Hsu Meier , Hawk Ernest T. , Eagle Craig J. , Zauber Ann G. 
Published: February 2011

Abstract
Discussant: John A. Baron, Dartmouth Medical School, Lebanon, NH.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-173.
Abstract LB-189: BRAFdeletion and pharmacological inhibition enhance K-ras driven tumorigenesis
Authors: Murriel Christopher L. , Chen Honglin , Kenski Denise , Bou-Reslan Hani , Yuan Wenlin , Liang Yuxin , Carano Richard , Couto Suzana , Seshagiri Somasekar , Davis David P. , Johson Leisa 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-189.
Abstract LB-191: Loss of the wild-type Kras allele enhances the cellular proliferation and metastasis of pancreatic ductal adenocarcinomas in a conditional P16 and Kras mutant mouse model
Authors: Qiu Wanglong , Sahin Fikret , Iacobuzio-Donahue Christine A. , Garcia-Carracedo Dario , Wang Wendy M. , Arking Dan E. , Lowy Andrew M. , Hruban Ralph H. , Remotti Helen E. , Su Gloria H. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-191.
Abstract LB-192: In vivo zebrafish tyrosine kinase assay for anti-cancer drug screening
Authors: Li Chun-Qi 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-192.
Abstract LB-197: Tumor vasculature associated marker as a target for recombinant DNA based vaccines
Authors: Facciabene Andrea , Facciponte John , Coukos George 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-197.
Abstract LB-202: STAT3 induces pituitary tumor transforming gene (PTTG) expression
Authors: Zhou Cuiqi , Ren Song-Guang , Tong Yunguang , Wawrowsky Kolja , Bannykh Serguei , Melmed Shlomo 
Published: February 2011

Abstract
PTTG is overexpressed in multiple human tumors, but mechanisms regulating tumor PTTG abundance remain elusive. As EGF induces pituitary cell PTTG expression, and as STAT3 is required for pituitary cytokine responses, we investigated STAT3 regulation of PTTG. STAT3 and PTTG were both concordantly overexpressed in 79 human pituitary tumor specimens (62% and 56% respectively; p&lt;0.01) as assessed by confocal immunofluorescence. We therefore treated ACTH-secreting AtT20 corticotroph tumor cells with IL-6 which dose-dependently increased STAT3 phosphorylation, PTTG and POMC expression. STAT3 also specifically bound to the human PTTG promoter (−2000 to −3000 bp) and induced PTTG transcriptional activity (2.2-fold) as assessed by chromatin immunoprecipitation and luciferase reporter assay, implying that PTTG acts as an intracellular STAT3 target. To elucidate the function of this pathway, we constructed WT STAT3, constitutively activated STAT3 (STAT3-C) and dominant negative STAT3 (STAT3-DN) plasmids, and selected respective stable transfectants. STAT3 transfection doubled PTTG mRNA and protein abundance, while PTTG induction was enhanced 3-fold in STAT3-C, and totally abrogated in STAT3-DN transfectants (0.7-fold). Stable STAT3 overexpression also enabled in vitro colony formation which was strongly attenuated by PTTG RNAi (∼50%, p&lt;0.01). Elevated STAT3 expression, or STAT3 activation, both increased HCT116 cell migration and invasion 5-fold as measured by in vitro cell assays, whereas cell mobility was abolished by STAT3-DN (&gt;90%). Knockdown of PTTG expression by RNAi strongly suppressed STAT3-induced cell migration and invasion by up to 80%. Attenuating PTTG expression by RNAi in STAT3-C stable cells constrained downstream myc, cyclin D3, K-Ras and MMP expression. Moreover, STAT3 inhibitor VI dose-dependently (10-150 M) suppressed STAT3 phosphorylation and subsequently inhibited PTTG, cyclin D3, POMC expression and ACTH secretion as treated for 24 hours. We also generated PTTG RNAi stable transfectants on STAT3-C stable cells and injected these compound transfectants s. c. to nude mice. PTTG RNAi decreased STAT3-C-induced in vivo tumor volume (32%, p&lt;0.01), compared to injected scrambled control transfectants which readily formed tumors. These results elucidate a mechanism for tumor PTTG abundance, whereby STAT3 activation induces PTTG expression to facilitate tumor formation. These findings further elucidate PTTG actions in tumor progression and support the rationale for targeting PTTG to abrogate endocrine tumor growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-202.
Abstract LB-204: Gene expression profiling of hormone-regulating pathways in tumoral and peritumoral breast tissues
Authors: Christine Flageole , Audet-Walsh Étienne , Bélanger Alain , Guillemette Chantal 
Published: February 2011

Abstract
Purpose: The purpose of our investigation was to study the mRNA expression of sex-steroids pathways involved in androgen and estrogen synthesis and metabolism in tumor and surrounding peritumoral normal breast tissues. High integrity RNA was purified and specific quantitative realtime PCR assays was performed to assess expression level of thirty two genes in breast tissues from the 4 quadrants of postmenopausal mastectomy patients diagnose with breast cancer. The expression changes between tumors (n=31) and paired normal (n=86) tissues were assessed using a general linear model on log-transformed data.
Results: The main pathway involved in estrogen synthesis in postmenopausal women, steroid sulfatase, was detected at lower levels in tumor tissues compared to non-malignant tissues. mRNA expression levels of aromatase converting androgen to estrogen were relatively constant between peritumoral normal and tumoral tissues while androgen conjugating enzymes leading to inactive metabolites were overexpressed in tumoral tissues (1.4-fold; P &lt; 0.04). Expression of CYP1A1, involved in the synthesis of 2-hydroxy-catecholestrogens, was constantly detected at lower level in tumors compared to peritumoral tissues (3.7 fold; P &lt; 0.001). However, no prominent changes for the catechol-o-methytransferase (COMT), involved in the conversion of 2-hydroxy-catecholestrogens to methoxy metabolites with cancer-protective properties, was noted. In contrast, CYP1B1 expression was enhanced by 1.7 fold in tumors (P &lt; 0.001) suggesting a greater in situ formation of 4-hydroxy-catecholestrogens, a group of metabolites associated with DNA damage and production of redox species. Data also reveal a lower expression in tumors of the NAD(P)H quinone oxydoreductase 2 (NQO2) most active against catechol estrogens (1.8-fold; P=0.04), while expression of NQO1 remained unchanged. These observations were further enhanced in estrogen receptor positive tumors.
Conclusion: Our data add to the emerging evidence of an imbalance in the production of androgen, estrogen and their metabolites in breast tumors, preferentially leading to the accumulation of carcinogenic metabolites while decreasing protective metabolites in neoplastic tissue compared to normal tissue.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-204.