bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3894: Copy number alterations in urothelial carcinomas: Their clinicopathological significance and correlation with DNA methylation alterations
Authors: Nishiyama Naotaka , Arai Eri , Nagashio Ryo , Fujimoto Hiroyuki , Hosoda Fumie , Shibata Tatsuhiro , Tsukamoto Taiji , Yokoi Sana , Imoto Issei , Inazawa Johji , Kanai Yae 
Published: June 2012

Abstract
Purpose: The aim of this study was to clarify the genetic backgrounds underlying the clinicopathological characteristics of urothelial carcinomas (UCs).
Experimental Design: We analyzed copy number alterations by array comparative genomic hybridization analysis using a high-resolution (244K) oligonucleotide array, DNA methylation alterations on a genome-wide scale using bacterial artificial chromosome array-based methylated CpG island amplification, and DNA methylation status on C-type CpG islands using bisulfite modification in 49 samples of UCs of the urinary bladder, ureter and renal pelvis. The clinicopathological significance of copy number alterations and the correlations between alterations of copy number and those of DNA methylation were examined.
Results: Losses of 2q33.3-q37.3, 4p15.1-q26 and 5q13.3-q35.2 and gains of 7p11.2-q11.23 and 20q13.11-q13.31 were correlated with higher histological grade, and gain of 7p21.2-p21.1 was correlated with deeper invasion. Losses of 6q14.1-q27 and 17p13-q11.1 and gains of 19q13.11-q13.12 and 20q13.12-q13.33 were correlated with lymph vessel involvement. Loss of 16p12.2-p12.1 and gains of 3q26.31-q29 and 20q13.2-q13.33 were correlated with vascular involvement. Losses of 5q14.1-q23.2, 6q14.1-q27, 8p22-p21.3, 11q13.5-q14.1 and 15q11.2-q22.2 and gains of 3q27.3-q29, 7p11.2-q11.22, 10p13-p12.33, 12q24.31 and 19q13.11-q13.2 were correlated with the development of aggressive non-papillary UCs. Losses of 1p33-p31.1, 2q22.1-q23.1, 10q11.23-q21.1 and 15q21.3 were correlated with tumor recurrence. Unsupervised hierarchical clustering analysis based on copy number alterations clustered UCs into three subclasses, clusters A, B1 and B2: copy number alterations associated with genome-wide DNA hypomethylation, regional DNA hypermethylation on C-type CpG islands associated with chromosomal losses, and genome-wide DNA hypo- and hypermethylation, were accumulated in clusters A, B1 and B2, respectively.
Conclusions: There is a need to explore tumor-related genes that may encode potential therapeutic targets at chromosomal loci where copy number alterations are correlated with clinicopathological parameters reflecting the malignant potential of UCs. Chromosomal loci where copy number alterations are correlated with UC recurrence may be potential indicators of prognosis. Both genetic and epigenetic events appear to accumulate during urothelial carcinogenesis, reflecting the clinicopathological diversity and histological heterogeneity of UCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3894. doi:10.1158/1538-7445.AM2011-3894
Abstract 3896: The interaction between BRCA2 and DSS1 is crucial for homologous recombination through controlling protein localization
Authors: Egashira Akinori , Siaud Nicolas , Christ Nicole , Morita Masaru , Kakeji Yoshihiro , Jasin Maria , Maehara Yoshihiko 
Published: June 2012

Abstract
The BRCA2 tumor suppressor plays an important role in the repair of DNA damage by homologous recombination (HR). Human BRCA2 is huge protein and is composed of several domains including DNA/DSS1 binding domain (DBD). DSS1 has shown to be important for HR in various organisms but the precise function of DSS1 through the interaction between BRCA2 is still unclear in mammalian cells. To clarify the role of DSS1-BRCA2 interaction in the repair of DNA damage, we put several mutations into BRCA2 peptides which could restore HR in Brca2 mutant hamster cells. The mutant BRCA2 peptides with mutation which reduced DSS1 binding impaired the ability of these peptides to promote HR when compared to wild type peptides. It is of great interest that the excessive DSS1 expression partially restored HR activity of BRCA2 mutants which weakly bind DSS1. Furthermore, excessive DSS1 expression facilitate the nuclear localization of wild type BRCA2 peptide. On the other hand, excessive DSS1 expression had no effect for neither HR activity nor the subcellular localization of mutant BRCA2 peptide that could not bind to DSS1. Knockdown of DSS1 by siRNA also showed reduced HR and nuclear localization of BRCA2 protein. In conclusion, one of the essential functions of DSS1 in HR through the interaction between BRCA2 might be a regulation of BRCA2 subcellular localization.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3896. doi:10.1158/1538-7445.AM2011-3896
Abstract 3897: A difference of HER-2 amplification index between luminal B and HER2 enriched subgroup
Authors: Lee Soohyeon , Koo Ja Seung , Park Byung Woo , Kim Seung Il , Park Se Ho , Kim Gun Min , Kim Se Hyun , Kim Joo Hang , Sohn Ju Hyuk 
Published: June 2012

Abstract
Background: The aim of this study was to compare the HER2 gene amplification index (AI) of luminal B and HER-2 enriched breast cancers using fluorescence in situ hybridization (FISH).
Methods: Out of 753 patients with breast cancer who were tested HER2 status by FISH between Jan 2004 to Dec 2009, 224 HER2 amplified patients were available for this study. HER2-amplified breast cancers constitute a heterogenous group that may be subdivided according to their ER status: HER2 amplified ER-positive breast carcinomas that fall into the luminal B group; and HER2 amplified ER-negative cancers which form a distinct molecular subtype, known as the HER2 enriched group according to hormone status by immunohistochemistry and HER2 amplification confirmed as HER2/CEP17 ratio by FISH. A difference of HER2 AI was analyzed between luminal B and HER-2 enriched group. Clinicopathologic parameters were analyzed.
Results: Among the HER2 amplified patients, the proportion of luminal B and HER2 breast cancer was 53.5% (N=120) and 46.5% (N=104), respectively. Early breast cancer patients were 84.8% (N=190) and metastatic breast cancer patients were 15.2% (N=34). HER-2 AI of luminal B group and HER2 enriched group were 4.99 and 5.84 respectively, which values showed the quantitative difference statistically significant (p=0.003). However, increasing value of HER2 AI was not associated with a better overall survival or progression free survival. In luminal B group, a significant difference of HER2 AI between ER/PR +/+ subgroup and ER/PR +/- subgroup existed which were 4.02 and 5.32, respectively (p=0004).
Conclusions: The HER2 AI of HER2 enriched group was higher than that of luminal B group statistically significant. It was not clear whether the extent of HER-2 amplification relates to the survival benefit of treatment in HER-2 positive breast cancer. Further research to understand how the level of HER2 amplification is related to prognosis is warranted in order to understand the breast cancer biology associated with the intrinsic subtypes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3897. doi:10.1158/1538-7445.AM2011-3897
Abstract 3899: Anti-cancer drugs increases microsatellite instability in human colorectal cancer cells
Authors: Chang Christina L. , Chiu Chien-Yuan , Chi Jhih-Ying , Wu Chang-Lin Wu Chang-Lin , Li I-Chen , Jian Siao-Ru 
Published: June 2012

Abstract
Manifested as microsatellite instability (MSI), DNA mismatch repair (MMR) deficiency is known to contribute to colorectal cancer pathogenesis and drug resistance. Growing evidence indicates that MMR deficiency is also widespread among secondary cancers in patients who have received chemotherapy. It is unclear what chemotherapeutic agents cause MMR deficiency. In this study, we aim at identifying the MSI-inducing anti-cancer drugs. To facilitate the identification, we developed an in-vivo dual fluorescent reporter system in a human colorectal cancer cell model using RFP that contains a microsatellite as the MSI reporter and GFP as the cell label. Based on flow cytometric analysis, we found that test anti-cancer drugs increased the MSI frequency in a dose-dependent manner. This was confirmed by fluorescent microscopy. With the NCI recommended markers, we detected a low frequency of MSI in cells after treated with a couple, but not all, of test anti-cancer drugs. Our cell-based MSI reporter assay will facilitate large scale screens of MSI-inducing and MSI-reducing drugs/compounds, which might provide treatment strategies for controlling therapy-related secondary cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3899. doi:10.1158/1538-7445.AM2011-3899
Abstract 3971: Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: Loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2
Authors: Nakahara Osamu , Takamori Hiroshi , Sakamoto Yasuo , Tanaka Hiroshi , Chikamoto Akira , Horino Kei , Beppu Toru , Honda Yumi , Iyama Ken-ichi , Baba Hideo 
Published: June 2012

Abstract
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) include various degree of dysplasia, and are supposed to be one of the precursors of pancreatic ductal adenocarcinoma (PDCA), however, IPMN carcinogenesis has not yet been established. MicroRNAs (miRNA) may be directly implicated in some carcinogenic process. These miRNAs can function as tumor suppressors or oncogenes. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target genes, and plays a pivotal role in the etiology of tumorigenisity in several cancers.
PURPOSE: This study aimed to (1) evaluate whether expression of EZH2 promotes neoplastic progression of IPMN and PDCA, and (2) elucidate regulation of EZH2 expression by miR-101.
METHODS: EZH2 mRNA and protein expression was investigated in eight human pancreatic cancer cell lines (PANC-1, PK8, PK9, PK-59, KLM-1, MIA PaCa2, Hs-700T, PK-45P) by PCR and western blotting. Pre-miR-101, and anti-miR-101 was transfected into pancreatic cancer cells to elucidate regulation of EZH2 by miR-101. To evaluate whether EZH2 modulates malignant progression of IPMN, EZH2 expression in both benign and malignant IPMN was examined in 54 patients by immunohistochemistry. Next, we collected malignant and benign cells from formalin-fixed paraffin-embedded samples of IPMNs using laser capture microdissection, and extracted RNA. MiR-101 expression in IPMN was assessed using real-time PCR.
RESULTS: All pancreatic cancer cell lines expressed EZH2 mRNA and protein. The induction of miR-101 by transfection of pre-miR-101 in MIA PaCa-2 was closely related to a reduction in EZH2 protein production compared with control, whereas there was little difference in the expression of EZH2 mRNA. Anti-miR-101 transfected pancreatic cancer cells showed increase in EZH2 protein, while EZH2 mRNA level was not elevated. Immunohistochemistry revealed that the expression of EZH2 was significantly higher in malignant than benign IPMN. Expression of MiR-101 was significantly lower in malignant than benign IPMN.
CONCLUSIONS: MiR-101 targets EZH2 at the posttranscriptional level, and loss of miR-101 could be a trigger for the adenoma-carcinoma sequence of IPMN by up-regulation of EZH2. This study suggests miR-101- EZH2 blockade as a potential therapeutic target in IPMN carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3971. doi:10.1158/1538-7445.AM2011-3971
Abstract 3981: miR-708 induces apoptosis and suppresses tumorigenicity in renal cell carcinomas
Authors: Saini Sharanjot , Yamamura Soichiro , Majid Shahana , Shahryari Varahram , Deng Guoren , Hirata Hiroshi , Ueno Koji , Chang Inik , Tanaka Yuichiro , Dahiya Rajvir 
Published: June 2012

Abstract
MicroRNAs (miRNAs) constitute an evolutionarily conserved class of small non-coding RNAs that primarily regulate gene expression at the post-transcriptional level via sequence-specific interaction with the 3’-untranslated regions of cognate mRNA targets. Recent evidence indicates that dysregulated miRNA expression leads to tumorigenesis and miRNAs have been implicated to function as either tumor suppressors or oncogenes. The main objective of the present study was to identify miRNA genes that regulate renal cell carcinomas (RCC). Towards this, we performed microRNA expression profiling in normal immortalized renal cell line (HK2) and primary renal cancer cell lines (A498 and Caki2) and identified that miR-708 expression is significantly attenuated in renal cancer cell lines. This attenuation was validated by RT-PCR and in situ hybridization analysis of miR-708 in RCC tissue specimens. Further, trichostatin A, a pharmacological inhibitor of histone deacetylases, strongly increased miR-708 levels in cell lines from renal cancer suggesting that epigenetic silencing may lead to miR-708 downregulation in RCC. To evaluate the functional significance of decreased miR-708 expression, miR-708 was reintroduced in renal cancer cell lines followed by functional assays. Overexpression of miR-708 in the A498 cell line leads to significant decreases in cell growth, clonability, invasiveness and migratory properties. Importantly, miR-708 reexpression leads to dramatic induction of apoptosis in A498 cells suggesting that restoration of miR-708 expression in A498 cells suppressed tumorigenecity in vitro by primarily affecting the apoptotic program. In vivo, intratumoral delivery of miR-708 led to a regression of tumor growth in established renal tumor xenografts. Further, analysis of putative miR-708 targets showed that miR-708 targets survivin/BIRC5, a small inhibitor of apoptosis (IAP) protein that plays a pivotal role in renal cancer progression. In conclusion, our data suggests a crucial tumor suppressive role for miR-708 in RCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3981. doi:10.1158/1538-7445.AM2011-3981
Abstract 3986: MicroRNA-155 regulates angiogenesis by targeting Von Hippel-Lindau (VHL) tumor suppressor
Authors: Kong William , He Lili , Tan Lei , Guo Jianping , Coppola Domenico , Coppola Marc , Cheng Jin Q. 
Published: June 2012

Abstract
Expression of microRNA-155 (miR-155) is frequently up-regulated in various types of human malignancy, including different forms of B cell lymphoma and carcinoma of breast, lung, colon, head/neck, and kidney; however, its role in cancer angiogenesis remains undefined. In this study, we demonstrate the critical role of miR-155 in regulation of angiogenesis through down-regulation of VHL; in addition we show elevated miR-155 levels in breast cancer correlates to high grade and late stage tumor as well as metastasis and poor overall survival. Stable ectopic expression of miR-155 in human umbilical vein endothelial cells induces tube formation in the absence of VEGF; whereas knockdown of miR-155 inhibits tube formation in the presence of VEGF. Further, we identified VHL as a direct target of miR-155. Stable overexpression of miR-155 results in repression of VHL protein; and knockdown of miR-155 rescues VHL expression. Introduction of VHL cDNA lacking 3’ untranslated region abrogates miR-155 induced tube formation. In addition, evaluation of miR-155 expression in primary breast cancers and normal mammary tissues show miR-155 high in 67 of 154 (43.5%) patients with breast cancer as compared to normal breast tissues. Elevated miR-155 is associated with high grade (49/76, 64.5%) versus low grade (18/78, 23.1%) and late stage (37/70, 52.9%) versus early stage (30/84, 35.7%) as well as invasive (53/85, 62.4%) versus non-invasive (14/69, 20.3%) breast carcinoma. Interestingly, miR-155 is also frequently overexpressed in lymph node-positive tumor (i.e., ≥ 10; 20/32, 62.5%) than node-negative (i.e., &lt; 10; 47/122, 38.2%). Furthermore, patients whose tumors express high levels of miR-155 have shorter overall survival than those of tumors with low levels of miR-155. Our findings indicate that miR-155 plays an important role in tumor angiogenesis by targeting VHL and could be a prognostic marker and a critical therapeutic target in breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3986. doi:10.1158/1538-7445.AM2011-3986
Abstract 40: Similarity-based exploration of genomic profiles in glioblastoma multiforme samples
Authors: Burton Julien , Petit Joachim , Fitzhugh Will , Berens Michael , Kiefer Jeffrey , Meurice Nathalie 
Published: June 2012

Abstract
The main goal of this study is to deploy similarity-driven methodologies to explore data in public repositories such as The Cancer Genome Atlas (TCGA).
One of the research goals of the In Silico Research Center of Excellence at TGen and 5am Solutions is to explore the differences and similarities between genomic profiles of glioblastoma xenografts, glioblastoma patient, and non-tumor samples and use that information to select a diverse but representative population of xenografts for drug-treatment experiments. The first step consists in designing similarity-driven methodologies to describe the relations in genomic datasets publicly available such as The Cancer Genome Atlas (TCGA). This contribution presents a workflow through which the similarity relationships amongst gene expression profiles from TCGA GBM and non-tumor samples are explored. The method consists in (1) representing the data as feature vectors, (2) calculating the pair-wise similarity between the objects based on the chosen representation and a similarity metric (e.g., euclidean distance), (3) projecting the obtained similarity matrix in the 3D space of its three first principal components, calculated by Principal Component Analysis (PCA).
The 3D similarity spaces obtained lead to several interesting interpretations: the different phenotypes (GBM, non-tumor, xenografts) were accurately depicted and reduced pools of genes (gene sets) could be used as sufficient description (Gene set enrichment analysis, caBIO gene sets) to conserve the initial representation.
These observations allowed us to validate the exploratory power of the method and to use it in further analysis such as the assessment of the similarity between xenografts and GBM samples to select appropriate treatments on a genomic likeness basis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 40. doi:10.1158/1538-7445.AM2011-40
Abstract 400: Modulation of the metastatic microenvironment by soluble factors released by lung adenocarcinoma cells
Authors: Carlini María J. , Vazquez Paula , Diament Miriam , Salatino Mariana , Rabinovich Gabriel A. , Bal de Kier Joffe Elisa D. , Puricelli Lydia I. 
Published: June 2012

Abstract
Soluble factors from primary tumors can modify target organs for metastasis through mobilization of bone marrow derived cells (BMDCs), which are recruited to tumors and to metastatic target organs and facilitate tumor growth and metastasis. Here we aimed to study early cellular and molecular events occurring in the lung, the metastatic target organ of the murine lung adenocarcinoma cell line LP07.
We assessed by flow cytometry the numbers of BMDC positive for VEGFR1, SCF, CD34 or CXCR4 and the numbers of myeloid suppressor cells (CD11b+/Gr1+) and regulatory T cells (CD4+/CD25+/FOXP3+) in single cell lung suspensions obtained from 15-day tumor-bearing and control mice. Control and tumor-conditioned lungs of inoculated mice showed comparable amounts of these cell populations. To assess whether the primary tumor stimulates subsequent formation of macroscopic metastasis, mice bearing an intraperitoneal millipore chamber -that allows the diffusion of soluble molecules but not cell extravasation- loaded with LP07 cells or medium, were challenged with a LP07 intravenous inoculum at day 15. The presence of LP07 loaded chambers decreased the number of lung metastases three weeks after the inoculum compared to control mice (p≪0.05). In a different approach, mice were daily injected for 15 days with LP07 conditioned medium or control medium, and then challenged with a LP07 intravenous inoculum. When evaluated at day 21 post LP07 cell inoculation, the number of metastatic lung nodules was significantly lower (p≪0.05) in the group treated with LP07 conditioned medium. Besides, when we assessed matrix metalloproteinase (MMP) activity in lung homogenates from 15 day-tumor bearing and control mice, we found a significant increase in MMP-9 activity (p≪0.05) as assessed by semi-quantitative zymography in lungs from tumor-bearing mice.In conclusion, in the LP07 lung adenocarcinoma model, tumor cells secrete soluble factors that induce certain changes in the metastatic target organ, as the increase of MMP-9 activity. Moreover, in this experimental metastatic approach, a decrease in metastasis development was observed; the mechanisms underlying this phenomenon deserve further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 400. doi:10.1158/1538-7445.AM2011-400