bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1996: Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns
Authors: Brannon A. Rose , Reddy Anupama , Seiler Michael , Arreola Alexandra , Chen Shufen , Moore Dominic T. , Pruthi Raj S. , Wallen Eric M. , Nielsen Matthew E. , Liu Huiqing , Ljungberg Börje , Zhao Hongjuan , Brooks James D. , Ganesan Shridar , Bhanot Gyan , Rathmell W. Kimryn 
Published: February 2011

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer and presents in the clinical setting with a heterogeneous and difficult to predict natural history. Previous research has suggested the existence of molecular subtypes of ccRCC, but these studies have failed to elucidate the pathways driving these subtypes or provide gene sets translatable to clinic. Given the common use of molecularly targeted therapies in the clinic, a better understanding of the underlying tumor biology would clearly augment treatment decisions. In this study, gene expression microarray data from 48 patients was analyzed with ConsensusCluster, software that uses unsupervised consensus clustering algorithms to identify the most optimal innate molecular subclasses. Without clinical or other classifying information, this analysis identified two distinct subtypes of ccRCC within the training set, labeled clear cell type A (ccA) and B (ccB). Based on the most well-defined arrays in each subtype, Logical Analysis of Data (LAD) defined a highly accurate set of 120 probes that could then be subsampled to classify additional tumors individually. The subclasses were substantiated in a validation dataset of 177 tumors and analyzed for clinical outcome, demonstrating that tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs. 2.0 years, p=0.002). When analyzed by both univariate and multivariate analysis, the classification schema independently associated with survival. Furthermore, gene set analysis of both datasets suggests that ccB tumors overexpress more immature and aggressive pathways, while ccA tumors overexpress classic ccRCC pathways of metabolism and angiogenesis. Therefore, using only patterns of gene expression, a small gene set was defined that classified ccRCC into two robust subclasses with distinct biological pathway expression and marked differences in clinical outcome. This classification schema, which is applicable to individual tumors, has implicit repercussions for influencing treatment decisions, defining biological mechanisms involved in ccRCC tumor progression, and directing future drug discovery.
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 1996.
Abstract 2079: Estrogen receptor alpha expression with miR-206 trans-acting regulation roles in breast cancer cell lines
Authors: Choi Young Eun , Song Junkyu , Jo Yong Hwa , Park Hyun Mi , Yoon Kyung-Sik ,   Department of Biochemistry and Molecular Biology(BK21 project), MRC for Bioreaction to ROS and Bio
Published: February 2011

Abstract
Estrogen receptor-alpha (ER-α) is present in 65% of human breast tumors. Tamoxifen(Tam) was only effective in ER-α expressed breast cancer cell lines. Also, it was reported that miR-206 decreases endogenous ER-α mRNA and protein levels in human MCF-7 breast cancer cells. We expect that effect of invasion and apoptosis in breast cancer cells by regulating expression of miR-206. Hence, we demonstrated that trans-acting regulation roles by ER-α and miR-206 in breast cancer cell line. MCF-7(ER hyper-expressed), MDA-MB231(ER hypo-expressed), MCF-10A(ER hypo-expressed normal breast cell line) cells were targeted experiments. Cell viability was analyzed by dose-dependent Tamoxifen with MTT assay. Whole-cell extracts were observed for protein levels of ER-α, ERK, p38, p-ATM, ATM, p-chk2, chk2, p-p53, p53, cyclinD1 with western blotting. By using, ER-α, p38, miR206 activator/inhibitor and real-time PCR, we studied change of molecules in cell lines. Cell viability of MCF-7 cell was reduced about 85% of the cells were dead by 5, 7μM Tam. ERK phosphorylation was increased by dose-dependent Tam in both MCF-7 cell and by 7μM Tam treatment in MDA-MB231 cell. Also, p38 phosphorylation was raised by dose-dependent Tam in MCF-7 cells and MDA-MB231 cells. ATM, chk2, p53 that involved DNA damage molecules were not affect by dose-dependent Tam. CyclinD1 known as cell cycle G1 regulation molecule was decrease by effect of Tam. Also, miR-206 levels by real-time PCR were lessening in MCF-7 and increase in MDA-MB231 and MCF-10A. Specific molecules of MCF-7, MDA-MB231 and MCF-10A were influenced by ER-α, p38, miR-206 activator/inhibitor. ER-α regulation and miR-206 expression were shown to trans-activated roles in breast cancer cell lines. Therefore, inhibition of miR-206 was accompanying the hyper-sensitivity of anticancer drug Tamoxifen that mediated ER-α. Whereas, miR-206 over expressed put down the invasion properties of breast cancer. We suggest that these roles of miR-206 will take the strategy for valuable breast cancer therapy.
Keywords: ER-α, miR-206, Tamoxifen, breast 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 2079.
Abstract 2104: MicroRNA-101 promotes estrogen independent growth and confers tamoxifen resistance in ER positive breast cancer cells
Authors: Sachdeva Mohit , Wu Hailong , Ru Peng , Hwang Larn , Trieu Vuong , Mo Yin Yaun 
Published: February 2011

Abstract
MicroRNAs function as key gene regulators capable of silencing gene expression at the posttranscriptional level. It is estimated that over 1/3 protein coding genes are under control of microRNAs. For example, estrogen receptor (ER) is negatively regulated by microRNAs such as miR-22 and miR-206, and a consequence of this suppression causes resistance to tamoxifen, a commonly used clinical anticancer drug for treatment of breast cancer. However, it is not clear whether microRNAs play any role in the estrogen independent growth, leading to intrinsic tamoxifen resistance. In this study, we use an in vivo selection system against a microRNA library. We first infect the ER positive MCF-7 cells with the pooled library and then orthotopically inject them into female nude mice without supplement of estrogen. As expected, MCF-7 cells infected with the library form tumors whereas those infected with vector control form no tumors. Further experiments show that a number of microRNAs including miR-101 are enriched. Importantly, miR-101 alone is able to promote estrogen independent growth and causes tamoxifen resistance. Unlike those microRNAs that confer tamoxifen resistance by targeting ER, miR-101 has no effect on ER expression or its activity. Of considerable interest, miR-101 suppresses cell growth in normal medium, but it promotes cell survival in estrogen free medium. Finally, we show that miR-101 is able to activate Akt in part due to suppression of Magi-2, a scaffold protein involved in regulation of pTEN activity. Hence, direct suppression of Magi-2 by miR-101 would provide a molecular link for miR-101-mediated activation of Akt through suppression of the pTEN activity. Taken together, these results demonstrate a novel function of miR-101. As a result, miR-101 may serve as a biomarker for the subpopulation of ER positive breast cancer patients who are intrinsically resistant to tamoxifen, and furthermore, it may serve as a novel therapeutic target for overcoming the resistance.
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 2104.
Abstract 2196: Genome-wide analysis of DNA methylation patterns in formaldehyde-fixed paraffin-embedded (FFPE) human tumor specimens
Authors: Brenet Fabienne , Socci Nicholas D. , You Daoqi , Cabal Rafael , Ladanyi Marc , Viale Agnes J. , Scandura Joseph M. 
Published: February 2011

Abstract
Formalin-fixed paraffin-embedded samples (FFPE) are in many case, the only available source of biological materiel available for translational studies. However the quantity and quality of nucleic acid extracted from FFPE samples is very often challenging (small amount and high level of degradation), which makes genomic analysis in general, and epigenomics analysis in particular, difficult to impossible. Here we are showing that we developed a robust, unbiased and cost effective method for genome-wide analysis of DNA methylation of FFPE DNA. Our method, named STAMP for Sequence Tag Analysis of Methylation Patterns, uses a recombinant protein containing a methyl-CpG binding domain (MBD) to precipitate methylated DNA fragments that are then identified by massively parallel sequencing using the SOLiD sequencer (ABI). We generate ∼15-million sequence tags per specimen and utilize an analytical platform comprised of custom-written R-language algorithms to study genomic DNA methylation patterns. We used this technology to compare the methylation patterns of matched fresh frozen (FF) and FFPE tumor specimens. Tissues had been stored for as long as 6 years. Because the STAMP method utilizes fragmented DNA as starting material we hypothesized that this method would be well-suited to the study of FFPE DNA methylation. Using this method, we found the methylation patterns of the FFPE and matched FF specimens were highly correlated. We successfully detected previously known methylated patterns and found hundreds of novel methylated regions. DNA methylation patterns were observed at all scales across the genome: from whole chromosomes to individual genes. We found that densely methylated elements are often highly conserved or closely associated with gene coding regions and promoters. We identified distinct patterns of DNA methylation surrounding the transcription start and termination sites of all genes. Genome-wide analyses of DNA methylation patterns of FFPE samples using the STAMP assay opens up the possibility to analyze large repositories of tumor specimens as well as samples that have been collected during routine clinical work and clinical trials. Large scales studies of DNA methylation using existing FFPE specimens linked to treatment outcomes may be rapidly translated to new epigenetic prognostic measures for cancer patients.
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 2196.
Abstract 2218: Whole exome DNA sequencing in human cancers of the digestive system
Authors: Wheeler David A. , Gingras Marie-Claude , Cotton Ronald , Guiteau Jacques , Hodges Sally , Wang Min , Wu Yuan-Qing , Newsham Irene , Nazareth Lynne V. , Fisher William E. , Goss John A. , Brunicardi Francis C. , Muzny Donna M. , Gibbs Richard A. 
Published: February 2011

Abstract
The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. The ever-expanding sequencing capacity ushered in by the second generation of DNA sequencers has enabled complete base-level description of the cancer genome and is therefore deepening our understanding of the etiology of the disease. We have combined a variety of approaches centered on next generation sequencing technologies aimed at comprehensive characterization of the cancer genome to define the key molecular lesions that drive tumor initiation and progression. These include targeted exonic sequencing to define coding sequence mutation, whole genome shotgun sequencing to define structural rearrangements, and cDNA sequencing to define alteration in expression levels, aberrant splicing and fusion transcripts. We have applied these approaches to pancreatic adenocarcinoma, hepatocellualr carcinoma and colorectal carcinoma. Results of genome sequencing have yielded an unprecedented picture of the rearrangements and mutations from analysis of read sequence and read coverage across the chromosomes. Evident in both the cancers is a dramatic reduction in SNP variation in the tumor genome compared to the germline from the same individual owing to extensive loss of heterozygosity. Superimposed on this are a few thousand mutations, some of which drive the tumor phenotype. The corresponding set of analog data generated by SNP-array microarray platforms provide validation of the central results from sequencing which leads to a new appreciation of the relationship between genetic change and the malignant phenotype.
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 2218.
Abstract 2225: Differential RNA splicing in high-risk neuroblastoma detected by affymetrix exon array and next-generation sequencing
Authors: Guo Xiang , Song Young , Badgett James , Chen Qing-Rong , Wei Jun , Khan Javed 
Published: February 2011

Abstract
RNA splicing is an important regulatory mechanism of gene expression providing various functions for specific cells including cancers. In this study, we investigated global alternative splicing pattern in neuroblastoma using Affymetrix exon array (HuEx) and deep sequencing approach (RNA-Seq). Exon array profiling was performed on 47 neuroblastoma samples in stage 1 and stage 4 with normal or amplified MYCN copy number (stage 1-, 4- and 4+). Principal component analysis demonstrated distinct splicing pattern in three groups of samples. In stage 4- compared with stage 1- tumors, differentially spliced candidate genes (n=355) had little overlap with genes showing whole gene expression changes (n=158), and most of them were involved in different biological processes. In contrast, a larger number of genes exhibited either exon-level splicing, gene-level expression, or both changes in stage 4+ versus stage 1- tumors. To validate exon array results, we performed transcriptome sequencing of selected samples with stage 1-, 4-, or 4+ neuroblastomas. The concept of splicing index was adapted to measure RNA splicing by short sequence reads. Both exon array and deep sequencing data demonstrated differential splicing of microtubule-associated genes, which may play an important role in enhanced genomic instabilities and tumor development. In conclusion, our results demonstrated a significant contribution of alternative or aberrant splicing to neuroblastoma development. The identification of differentially spliced genes and pathways in high risk neuroblastomas may be essential to the understanding of cancer biology and the discovery of diagnostic biomarkers or therapeutic targets in neuroblastoma.
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 2225.
Abstract 224: Antitumorigenic effect of synthetic C-substituted diindolyl methanes originating from cruciferous vegetables in KB human oral cancer cells through endoplasmic reticulum stress
Authors: Choi Eun-Sun , Shim Jung-Hyun , Cho Sung-Dae , Cho Nam-Pyo 
Published: February 2011

Abstract
Diindolylmethane (DIM), an isothiocyanates found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC6H5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of KB human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of Death Receptor 5 and the cleavage of bid and caspase 8. Mechanistic studies demonstrated that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum (ER) stress. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in KB cells via the ER stress pathway.
This study was supported by Bio R&D program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (M10870050003-08N7005-00311) and National Research Foundation of Korea Grant funded by the Korean Government (KRF-2008-331-E00260).
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 224.
Abstract 2282: Inhibition of vasculogenesis, but not angiogenesis, reduces tumor recurrence following irradiation
Authors: Brown Martin , Kioi Mitomu , Ahn G-one 
Published: February 2011

Abstract
Tumor blood vessels can derive from two sources: by angiogenesis, or the sprouting of endothelial cells from nearby blood vessels, and by vasculogenesis, which is produced by circulating cells. We have proposed that the radiation doses given in radiotherapy, will severely restrict local angiogenesis and thereby force tumor regrowth to rely on vasculogenesis. This involves the recruitment of proangiogenic circulating cells many of which are derived from the bone marrow. To investigate this hypothesis, we used the subcutaneously implanted FaDu human head and neck tumor and an orthotopic brain tumor using human U251 GBM cells.
We found that local tumor irradiation induced the influx of bone marrow derived cells (BMDCs) in a dose-dependent manner into both tumor models with most of this increase reflecting influx of CD11b+ myelomonocytes. We postulated that this influx of BMDCs was stimulated by increased tumor hypoxia and HIF-1 levels caused by radiation damage to the tumor vasculature. To determine HIF-1 activity in real-time in our brain implanted U251 GBM, we stably expressed the HIF-1 reporter construct 5HRE-luc in U251 cells and showed that HIF-1 activity increased rapidly starting at about two weeks following 15 Gy, in parallel to the increase in tumor hypoxia that we observed at this time.
To test our hypothesis that the increased HIF-1 levels were responsible for the increased influx of CD11b+ cells into the tumors, we used the HIF-1 inhibitor NSC-134754. When this was given daily for 2 weeks, starting immediately following irradiation, the increased tumor levels of CD11b+ monocytes observed after 15 Gy was abrogated. This treatment also prevented the regrowth of the irradiated tumors following irradiation.
As a further test of our hypothesis we determined the effect of inhibiting the interaction of SDF-1 with its receptor CXCR4 using the clinically approved drug AMD3100, which we infused starting immediately following irradiation. This had no effect on the growth of unirradiated tumors in the brain but completely inhibited the recurrence of the irradiated tumors following either a single dose of 15 Gy or the more clinically relevant scheme of 5 daily doses of 2 Gy. Inhibition of angiogenesis with DC101 increased tumor growth delay but did not prevent tumor recurrences.
We also showed that the recurrence of FaDu tumors locally irradiated with 20 Gy was prevented using a monoclonal neutralizing antibody against CD11b+ monocytes. This treatment did not increase the radiosensitivity of normal skin thereby providing a therapeutic gain.
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 2282.
Abstract 2289: MRJ(L) reverts mesenchymal phenotype and restricts malignancy by inhibiting Wnt/β-catenin signaling
Authors: Samant Rajeev S. , Mitra Aparna , Menezes Mitchell E. , Shevde Lalita A. 
Published: February 2011

Abstract
Expression of MRJ (Hsp40/DNAJB6) is lost in advanced infiltrating ductal carcinoma. We found that ectopic expression of the large isoform of MRJ, MRJ(L), is functionally capable of retarding tumor growth. Our continuing efforts towards understanding the effect of MRJ(L) expression on cancer cells revealed that MRJ(L) caused morphological changes indicative of epithelial-like appearance. It decreased the expression of several mesenchymal markers such as N-cadherin, Twist, Slug, vimentin and up regulated epithelial marker, Keratin 18. However, most noticeable was the loss of β-catenin protein upon MRJ(L) expression. Differential-proteomic analysis of the secretome showed that MRJ(L) expression elevated DKK1 (Dickkopf1), a secreted inhibitor of Wnt/β-catenin signaling. Increased DKK1 levels enhanced proteosome mediated degradation of β-catenin and reduced Wnt/β-catenin signaling as measured by the TCF/LEF reporter activity in MRJ(L) expressors. Furthermore we found that silencing MRJ(L) from immortalized mammary epithelial cell line, MCF10A, led to decreased DKK1 and E-cadherin levels, with concomitant increase of β-catenin protein. We also found that silencing DKK1 from the MRJ(L) overespressing cancer lines led to increased malignant behavior as measured by foci formation, growth in soft agar and wound healing capacity. Overall, our findings lead us to conclude that MRJ(L) maintains the epithelial phenotype and restricts malignant behavior of tumor cells by inhibiting Wnt/β-catenin pathway.
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 2289.