bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2893: Integrated genomic meta-analysis of colorectal cancer by elastic-net.
Authors: Lee HoJoon , Flaherty Patrick , Ji Hanlee P. 
Published: August 2014

Abstract
To identify combinatorial sets of known, putative and new cancer drivers responsible for colorectal cancer (CRC) development and other associated specific clinical outcomes, we have developed an integrative analysis method for cancer genome data. This approach is based on the elastic-net algorithm that we have applied to genomic data from the Cancer Genome Atlas (TCGA) Project. Our supervised analysis simultaneously assesses the contribution of i) copy number variation (CNV), ii) gene expression, iii) miRNA, iv) methylation and v) cancer mutations to clinical features. The ongoing TCGA project is generating genomic and clinical data sets from different tumor types including CRC. These detailed catalogues of genetic changes in cancer genomes will continue to provide us with new insights about cancer development. However, extracting biologically/clinically relevant information from TCGA's diverse and large cancer genome data remains a challenge. In attempt to overcome this challenge, we use regularized regression method: elastic-net that improves on “the least absolute shrinkage and selection operator” (Lasso). To demonstrate the performance and validity of this approach, we showed that elastic-net successfully identified i) synthetic genes that have their CNVs perfectly associated with stages from a simulated data ii) TGFBR2 and other driver genes that have mutations associated with CRCs that demonstrate microsatellite instability CRC from TCGA data, and iii) IDH1 that obtained mutations associated with survival according to glioblastoma (GBM) data. In the next phase of the study, we identified the top ranked genes that delineate key clinical features such as TNM stages of CRC. We have identified a series of candidate genes that may indicate clinical stages including novel candidates on chromosome 8. Overall, we have successfully demonstrated that our approach allows for an integrative and highly robust supervised analysis of TCGA data.
Citation Format: HoJoon Lee, Patrick Flaherty, Hanlee P. Ji. Integrated genomic meta-analysis of colorectal cancer by elastic-net. [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 2893. doi:10.1158/1538-7445.AM2013-2893
Abstract 2899: Significance of microRNA:target interaction in bladder cancer metastasis.
Authors: Ru Yuanbin , Kechris Katerina J. , Smith Steven C. , Calin George A. , Theodorescu Dan 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through base pairing with other mRNA transcripts. MiRNA expression signatures have characterized many phenotypes in bladder cancer, including grade, stage, and metastasis. However, simultaneous mRNA changes accompanying the miRNA profile, along with the miRNA:mRNA interaction, have not been systematically studied in these phenotypes. To gain insights into the miRNA regulatory network in bladder cancer metastasis, we profiled miRNA and mRNA expression in two pairs of metastatic and non-metastatic cell lines. Interactions between differentially expressed miRNAs and mRNAs were predicted using 6 software programs. The candidate miRNA:mRNA pairs were further selected by their clinical relevance, including their expression in grade, stage, and tumor in 2 cohorts totaling 256 human tumors. We identified more miRNA:mRNA pairs with up-regulated miRNAs and down-regulated genes in metastatic cells than the pairs with down-regulated miRNAs and up-regulated target genes. The novel overexpression of one of the miRNAs, hsa-miR-146a, was confirmed by quantitative RT-PCR in metastatic cell lines. It has been shown that decreased level of hsa-miR-146a is associated with progression of prostate cancer and polymorphism in hsa-miR-146a gene is associated with prostate cancer risk. We are carrying out in vitro and in vivo experiments on the top 5 scoring pairs ranked by the number of prediction software and clinical relevance. Our results suggest the significance of miRNA regulatory network in cancer metastasis and provide a list of potential miRNA:mRNA pairs for further investigation.
Citation Format: Yuanbin Ru, Katerina J. Kechris, Steven C. Smith, George A. Calin, Dan Theodorescu. Significance of microRNA:target interaction in bladder cancer metastasis. [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 2899. doi:10.1158/1538-7445.AM2013-2899
Abstract 2900: Phylogenetic classification, structural evolution, and functional divergence of the Ras superfamily of GTPases as tracked by the Conserved Domain Database (CDD)..
Authors: Song James S. , Thanki Narmada , Derbyshire Myra K. , Gwadz Marc , Gonzales Noreen R. , Marchler-Bauer Aron , Bryant Stephen H. 
Published: August 2014

Abstract
The Conserved Domain Database (CDD, http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml) is part of NCBI's Entrez query and retrieval system and is a collection of annotated multiple sequence alignment (MSA) models representing ancient conserved protein domains, basic units of protein function and protein evolution.These MSA models are available as position specific score matrices (PSSMs) for fast identification of conserved domains in protein sequences via Reverse Position Specific -BLAST (RPS-BLAST), a variation of the commonly used PSI-BLAST. The domain models can be viewed and examined interactively using NCBI's CDTree/Cn3D software applications. Conserved functional annotations such as key catalytic and ligand-binding sites are displayed on protein structures sharing significant homology to the query, thereby inferring the underlying mechanism(s) of the protein domain family. Here, we present the current, functionally annotated, evolutionary classification of the Ras GTPase superfamily, including the circularly permuted Ras-like domain, and its downstream effectors such as RasGAP and RasGEF. Using CDTree/Cn3D tools, subfamilies in diverse organisms were inferred from the MSAs, phylogenetic trees, and domain architectures of the Ras superfamily. Furthermore, several subfamilies comprising of only uncharacterized protein sequences have their functions annotated by inference from the molecular and cellular functions of known related proteins having 3D structure, and based on the available literature. We demonstrate the utility of CDTree/Cn3D in studying molecular evolution of protein domain families, and in accelerating the pace of biological discovery by enabling researchers to obtain valuable clues regarding as-yet-unidentified molecular properties and mechanisms. CDTree/Cn3D software is freely available for download via the CDD website.
Citation Format: James S. Song, Narmada Thanki, Myra K. Derbyshire, Marc Gwadz, Noreen R. Gonzales, Aron Marchler-Bauer, Stephen H. Bryant. Phylogenetic classification, structural evolution, and functional divergence of the Ras superfamily of GTPases as tracked by the Conserved Domain Database (CDD). [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 2900. doi:10.1158/1538-7445.AM2013-2900
Abstract 2904: An integrative analysis to identify putative drugs for acute myeloid leukemia.
Authors: Chen Yu-Heng , Hsiao Tzu-Hung , Chen Hung-I Harry , Chen Yidong , Chuang Eric Y 
Published: August 2014

Abstract
It is a time-consuming procedure to find an effective drug under current drug development, but the response rates of most anti-cancer drugs were still not high. Furthermore, the survival time of malignant cancer patients were often not prolonged after treatment. Therefore, to facilitate the process of discovering promising drug treatment, we proposed a novel integrative analysis based on gene set enrichment and evaluate the proposed model in acute myeloid leukemia (AML). The analysis was comprised by two methods. First, the enriched biological functions of each drug were identified based on the enrichment analysis of connectivity map, which is an expression profile of more than 950 drug treatments in the HL60 AML cell line. Second, the tumor progression associated functions were identified by using survival analysis. Finally, we integrated the results of two methods to generate a “drug - biological function - cancer” network. Based on the identified network, the putative anti-cancer drugs can be further explored. We applied a AML cohort data set, GSE12417, which contains 163 expression profiles, to our analysis framework. The result showed 429 enriched biological functions were related to 948 drugs. Among them, 21 of the 429 functions were identified as tumor progression associated functions though cox regression analysis. By integrating the two results, finally 174 putative drugs for AML were discovered. Our preliminary results provide valuable information to revisit the putative drugs to “reposition” for cancer therapy through identified biological functions.
Citation Format: Yu-Heng Chen, Tzu-Hung Hsiao, Hung-I Harry Chen, Yidong Chen, Eric Y Chuang. An integrative analysis to identify putative drugs for acute myeloid leukemia. [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 2904. doi:10.1158/1538-7445.AM2013-2904
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2907: Role of reactive oxygen and nitrogen species in resveratrol-induced lung cancer cell death.
Authors: Monillas Elizabeth S. , Walker Grayson , Brockmiller Aubrey , Iyer Anand , Azad Neelam 
Published: August 2014

Abstract
Lung cancer is the leading cause of cancer related deaths worldwide. In 2008, 158,592 deaths were attributed to this disease and 208,493 new cases were diagnosed in the United States. Resveratrol (trans-3, 5, 4′-trihydroxystilbene), a compound found largely in the skins of red grapes, has been reported to be a promising anticancer agent in various types of cancer. The primary goal of this study is to delineate the key signaling pathways induced in response to resveratrol leading to lung cancer cell death. In this study, we use non-tumorigenic human bronchial epithelial (BEAS-2B) and human lung epithelial cancer (H460) cells to model the response of lung tissue to resveratrol.
We observed an increase in superoxide, hydrogen peroxide and nitric oxide production in response to resveratrol treatment in lung cancer cells (H460) as compared to non-tumorigenic cells (BEAS-2B). Additionally, our data shows an increase in BEAS-2B cell viability as compared to H460 cell viability in response to resveratrol treatment. Overall, we observe an increase in cellular oxidative and nitrosative stress in cancer cells in response to resveratrol treatment which may be responsible for increased apoptosis and decreased viability in these cells. Subsequently, we plan to identify the specific reactive species as well as the major apoptotic pathway induced in response to resveratrol treatment in both normal and cancer cells. We expect resveratrol to have significant effect on lung cancer cells via oxidative/nitrosative stress-mediated modulation of key apoptotic biomarkers. This study will establish the protective role of resveratrol in the pathogenesis of lung cancer and the information can be potentially exploited to improve future lung cancer therapies.
Citation Format: Elizabeth S. Monillas, Grayson Walker, Aubrey Brockmiller, Anand Iyer, Neelam Azad. Role of reactive oxygen and nitrogen species in resveratrol-induced lung cancer cell death. [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 2907. doi:10.1158/1538-7445.AM2013-2907
Abstract 2908: Function and regulation of peroxiredoxin proteins in doxorubicin-treated MCF-7 breast cancer cells.
Authors: McDonald Caitlin , Perlmutter Gregg , Taparra Kekoa , Muhlbauer Jillian , Passarelli Julie , Phelan Shelley A. 
Published: August 2014

Abstract
The Peroxiredoxin (Prdx) family of genes encodes thiol-specific antioxidant proteins that protect cells from oxidative stress. Mammalian cells express six different Prdx proteins, and these proteins play a role in cell signaling, proliferation and apoptosis. Recent studies have shown that Prdx levels are elevated in many cancers, suggesting that Prdx upregulation may be an advantageous adaptation to the cancerous state. In the present study we investigated the expression and function of different Prdx proteins in untreated and doxorubicin-treated MCF-7 breast cancer cells, as well as noncancerous MCF-10A cells. We used real-time PCR and western blotting to examine Prdx expression in both cell lines, and also measured Prdx protein expression in doxorubicin-treated MCF-7 cells. In addition, we suppressed Prdx expression using transiently transfected siRNA and measured cell proliferation and apoptosis. Our results show that MCF-7 cells are significantly more resistant to cell death induced by the chemotherapy agent doxorubicin. We also found that five of the six Prdxs are overexpressed in MCF-7 cells at the mRNA and protein levels, and that serum deprivation reduced Prdx expression. Treatment of MCF-7 cells with doxorubicin altered expression of specific Prdxs, demonstrating a specific effect on these antioxidants. Transient transfection of MCF-7 cells with Prdx6 siRNA resulted in a marked reduction in Prdx6 suppression, with no change in other Prdx proteins. Suppression of Prdx6 in these cells led to reduced cell proliferation and increased susceptibility to doxorubicin-induced death. Similar studies are currently underway for the other Prdx proteins. Together, these findings suggest that Prdx overexpression in MCF-7 cells may be cytoprotective and that Prdxs may contribute to doxorubicin-resistance in these and other breast cancer cells.
Citation Format: Caitlin McDonald, Gregg Perlmutter, Kekoa Taparra, Jillian Muhlbauer, Julie Passarelli, Shelley A. Phelan. Function and regulation of peroxiredoxin proteins in doxorubicin-treated MCF-7 breast cancer cells. [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 2908. doi:10.1158/1538-7445.AM2013-2908
Abstract 2910: Suppressing excessive reactive oxygen species accumulation by RIP1 potentiates BPDE-induced transformation of human bronchial epithelial cells.
Authors: Wang Qiong , Chen Wenshu , Xu Xiuling , Li Bilan , He Weiyang , Padilla Mabel T. 
Published: August 2014

Abstract
Cell survival signaling is important for the malignant phenotypes of cancer cells. Although the role of receptor-interacting protein 1 (RIP1) in cell survival signaling is well documented, whether RIP1 is directly involved in cancer development has never been studied. In this report, we found that RIP1 expression is substantially increased in human non-small cell lung cancer (NSCLC) tissues and cell lines. RIP1 expression in human bronchial epithelial cells (HBECs) was significantly induced by cigarette smoke extract (CSE) or benzo[a]pyrene diol epoxide (BPDE), the active form of the tobacco-specific carcinogen benzo (a) pyrene (BaP). In RIP1 knockdown HBECs, BPDE-induced cytotoxicity was significantly increased, which was associated with induction of cellular reactive oxygen species (ROS), mainly hydrogen peroxide (H2O2), and activation of mitogen-activated protein kinases (MAPKs) including JNK, ERK and p38. Scavenging ROS suppressed BPDE-induced MAPK activation and inhibiting ROS or MAPKs substantially blocked BPDE-induced cytotoxicity, suggesting ROS-mediated MAPK activation is involved in BPDE-induced cell death. The H2O2-reducing enzyme catalase is destabilized in an ERK- and JNK-dependent manner in RIP1 knockdown HBECs and application of catalase effectively blocked BPDE-induced H2O2 accumulation and cytotoxicity. Importantly, BPDE-induced transformation of HBECs was significantly reduced when RIP1 expression was suppressed. Altogether, these results strongly suggest an oncogenic role for RIP1, which promotes malignant transformation through protecting DNA-damaged cells against carcinogen-induced cytotoxicity associated with excessive ROS production.
Citation Format: Qiong Wang, Wenshu Chen, Xiuling Xu, Bilan Li, Weiyang He, Mabel T. Padilla. Suppressing excessive reactive oxygen species accumulation by RIP1 potentiates BPDE-induced transformation of human bronchial epithelial cells. [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 2910. doi:10.1158/1538-7445.AM2013-2910
Abstract 2911: APE1/Ref1, a mammalian DNA repair/redox factor, increases mitochondrial activity.
Authors: Rangaswamy Suganya , Yarana Chontida , Miriyala Sumitra , Izumi Tadahide 
Published: August 2014

Abstract
The mammalian apurinic/apyrimidinic endonuclease 1 (APE1) is an essential DNA repair protein which also functions as a redox sensor (Ref1) to activate many transcription factors. A fraction of APE1/Ref1 protein is localized in the mitochondria for repairing oxidative DNA damage. However, its influence on mitochondrial activity has not been studied. We established genetically modified mouse embryonic fibroblast cells with extremely low APE1, at only 0.2% of the control MEFs. The APE1-knockdown (APE1kd) MEFs grew normally although they were highly sensitive to alkylating reagents. We analyzed the APE1kd MEFs to investigate the effect of APE1 on mitochondrial activity. Compared to the wild-type MEFs, the APE1kd MEFs exhibit a markedly decreased mitochondrial respiration activity and in turn showed glycolysis at a rate higher than the wild-type cells, which presumably compensated low ATP generation from mitochondria. A glycolysis inhibitor, 2-deoxy-D-glucose (2DG) affected ATP generation effectively, suggesting that the cells with low APE1 expression depended on glycolysis much more than the wild-type MEFs. The change in the mitochondrial activity appeared reversible. We propose that the presence of APE1 in the mitochondria/cytoplasm enhances mitochondrial respiration by a mechanism unrelated to its DNA repair activity.
Citation Format: Suganya Rangaswamy, Chontida Yarana, Sumitra Miriyala, Tadahide Izumi. APE1/Ref1, a mammalian DNA repair/redox factor, increases mitochondrial activity. [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 2911. doi:10.1158/1538-7445.AM2013-2911
Abstract 2912: Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumor initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells.
Authors: Chen Hsing-Yu , Yang Yin , Stevens Brett , Noble Mark 
Published: August 2014

Abstract
Two of the substantial challenges in cancer research are to identify means overcoming resistance of malignant cells to existing therapies and to eliminate the unique small population within bulk tumors, named tumor initiating cells or cancer stem cells which have been proposed to regenerate resistant relapsed tumors. In this study, we offer a novel therapeutic target relevant to both of these goals on basal-like (triple-negative) breast cancer (BLBC) cells, one of the most challenging cancers to treat with current regimens.
Our findings emerged from examining the puzzling differences in regulation of activation of the E3 ubiqutin ligase c-Cbl in normal cells and in cancer cells by low microM concentrations of tamoxifen (TMX). In normal progenitor cells, TMX causes oxidation and sequential activation of Fyn kinase and the c-Cbl ubiquitin ligase. Activation of c-Cbl via this redox/Fyn/c-Cbl (RFC) pathway leads to accelerated degradation of receptor tyrosine kinases that are critical in cell survival and division (such as the epidermal growth factor (EGFR)). In BLBC cells, in contrast, TMX does not activate c-Cbl despite making the cells more oxidized and causing activation of Fyn. Moreover, BLBC cells exposed to TMX show no reduction in levels of EGFR.
We found that TMX-induced activation of c-Cbl in BLBC cells was inhibited due to expression of Cdc42. Cdc42 sequestered c-Cbl, prevented its activation and prevented EGFR from being degraded. Restoration of c-Cbl function, by inhibiting activation of Cdc42, reduced EGFR levels in these cells. More critically, restoring c-Cbl function sensitized these cells to TMX both in vitro and in vivo through estrogen receptor-independent mechanisms. Analysis of tumor growth and formation in vivo showed that reducing the levels of Cdc42 reduced the size of tumors, increased sensitivity to TMX and decreased tumor forming capacity of these cells.
The results provide a novel defense mechanism that BLBC cells utilize to prevent EGFR degradation, which may have high relevance to treatment of these tumors. Of particular importance is the ability of cdc42 to confer TMX sensitivity on these otherwise resistant tumor cells. Moreover, as use of low microM levels of TMX has been attempted for over a dozen different kinds of cancers, at least some of which express increased levels of Cdc42, this strategy may be relevant to the treatment of multiple different cancers.
Citation Format: Hsing-Yu Chen, Yin Yang, Brett Stevens, Mark Noble. Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumor initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells. [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 2912. doi:10.1158/1538-7445.AM2013-2912