bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4930: Integrative analysis of genome-wide methylation and expression profiles for metastatic colorectal cancer
Authors: Midorikawa Yutaka , Tsuji Shingo , Nagae Genta , Takayama Tadatoshi , Sugiyama Yasuyuki , Aburatani Hiroyuki 
Published: August 2012

Abstract
In colorectal cancer (CRC) care, treatment decisions depend on efforts to estimate the metastatic potential of tumors. The liver is one of the most common metastatic sites of CRC and prognosis of CRC patients often reflects metastases to distant sites. However, the molecular mechanisms for further development of CRC with metastasis to the liver, lung, brain, bone and lymph nodes are unknown. The aim of this study was to stratify patients based on DNA methylation status and identify not one biomarker gene, but functional motif for metastatic potential of CRC. Using Illumina HumanMethylation 27 harboring approximately 27,000 CpG loci, we performed genome-wide methylation analysis for 74 CRC samples including 36 patients with liver metastasis and 38 without any distant metastasis. As a control, their corresponding colorectal mucosa was used. Consistent with our previous data, using non-negative matrix factorization and consensus clustering analysis, samples were clustered into three groups; high-, intermediate-, and low-methylation epigenotypes. Next, tumor samples were classified based on gene expression profile in each methylation cluster. Gene Set Enrichment Analysis was applied for expression data, which could identify that Rhodopsin kinase was activated in CRC samples with liver metastasis. Then genes included in this kinase were analyzed by Network Hidden Key molecule miner (NetHike) algorithm. NetHike, which we recently developed as network analysis, demonstrated that CXCR4 was one of key molecule for liver metastasis of CRC. In NetHike algorithm, several information such as methylation status and gene expression was inputted which would be integrated on known signaling pathways. In CXCR4 and its neighbors as a functional motif of CRC metastasis, CXCL12 was methylated without gene expression aberration. On the other hand, CXCR4, CCR5, and ARRB2 were not methylated, of which expression was increased, suggesting that integration and mapping of some gene information effectively identify activated gene pathways in some clusters, and may be missed only by conventional analyses. Taken together, network-based analysis could find the potential functional motif and integration of various gene expression aberrations and methylation status also could stratify CRC patients with liver metastasis and without metastasis. We plan to make an exhaustive exploration to discover the some novel functional topologies that have both expression and methylation aberrations and might be related to the mechanism of CRC metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4930. doi:1538-7445.AM2012-4930
Abstract 4933: Novel insight into hallmark switch in cancer metabolism using the Interrogative Biology™ discovery platform
Authors: Narain Niven R. , Vishnudas Vivek , Grund Eric , Lee Arleide , Alonzo Judith , Agarwal Shiuli , Caprice John , Khalil Iya , Akmaev Slava , Hill Colin , Sarangarajan Rangaprasasd 
Published: August 2012

Abstract
Cancer metabolism is an intergrative ensemble of disrupted enzyme kinetics and dysregulated metabolite utilization leading to loss of normal cellular function that is the result of a multi-factorial yet coordinated breakdown in vascular, immune, cell cycle, apoptotic, and ECM components. In actively metabolizing cancer, the switch from mitochondrial OXPHOS to anaerobic glycolysis is very well characterized and understood. Global cellular changes in response to metabolic switch have either been overlooked or not been primary interest or relevance to cancer metabolism. We describe a novel systems biology/engineering approach encompassing cell models that are conditioned under various oncogenic perturbations or environments and then coupled with functional bioenergetic read out such as employing the XF24 Seahorse Bioscience analyzer, ATP assays, and ROS production. The OCR and ECAR measurements generated by XF24 analyzer enabled quantifying the switch from aerobic to the anerobic mode of energy metabolism. Cellular profiles were captured in the form of multi-omic (proteomic, genomic, proteomic) signatures using high-throughput mass spectrometry based protocols. Analyses were performed on oncogenic breast, prostate, liver, pancreatic, skin (melanoma, squamous cell carcinoma) and were compared to normal fibroblasts, keratinocytes, hepatocytes, kidney cells, adipocytes, and human aortic and endothelial cells. High throughput data cascades from various cancer states were integrated with the metabolic data from the XF24 analyzer using an AI-based data mining platform to generate causal network based on bayesian models (REFS™ model). The output enables the understanding of differential mechanisms that drive glycolysis and mitochondrial OXPHOS in a cancer versus normal environment. Further validation of prominent hub of activity as they partake as key drivers of metabolic end points by siRNA knockdown experiments followed by measurement using the XF24 analyzer confirmed the relevance of these hubs in cancer metabolism and their relevance as potential therapeutic targets and biomarkers for diagnostics development. The data output presented herein strongly suggest that the Interrogative Biology® platform is a key tool in deciphering differential network analysis pertinent to disease pathophysiology and bioenergetics.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4933. doi:1538-7445.AM2012-4933
Abstract 4946: Control of cellular proliferation by ERK: A quantitative analysis in single cells
Authors: Albeck John G. , Mills Gordon B. , Brugge Joan S. 
Published: August 2012

Abstract
The EGF-stimulated ERK/MAPK system is a key conduit for physiological growth signals. We have used a combination of live and fixed single-cell measurements to determine the quantitative operating principles of this pathway under long-term stimulation by physiological levels of EGF, revealing three essential properties of the network. First, the extracellular concentration of EGF is encoded, at different points in the network, by distinct frequency- and amplitude-modulated responses. Second, control of cellular proliferation is controlled predominantly by the lower end of the pathway's dynamic range, necessitating nearly complete inhibition of the pathway to elicit growth arrest. Third, the diverse phenotypic outputs of the pathway are controlled by different segments of the overall dynamic range, with distinct molecular targets engaged at different thresholds. These properties have direct relevance to strategies for therapeutic inhibition of the ERK/MAPK network.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4946. doi:1538-7445.AM2012-4946
Abstract 4947: Analysis of structural mutations in cancer genomes
Authors: Woo Xing Yi , Menghi Francesca , Inaki Koichiro , Gong Min , Hillmer Axel , Sherbaf Faranak , Liu Edison 
Published: August 2012

Abstract
In our group, we have extensively sequenced various cancer genomes (breast cancer, ovarian cancer and melanoma) using a range of genome-wide sequencing approaches, including DNA-PET, RNA-SEQ and exome-capture sequencing. Taking each tumor as a system of its own, we aim to integrate the different outputs of these technologies to explore the composite of hard-wired changes that drive tumorgenesis in different cancers. One type of hard-wired changes is copy number alterations, where the cancer genome tends to gain oncogenes and lose tumor suppressors by DNA amplifications and deletions respectively. While copy number variation data are now a standard output of the DNA-PET pipeline, the accurate prediction of copy number gains and losses is further complicated by several issues, including normal tissue contamination, tumor heterogeneity and aneuploidy. I will present my current work to deconvolute the contribution of these factors to the copy number profile. I will also discuss the classification of our sequenced cancer genomes into various chromotypes based on their unique copy number signatures. I will show how different chromotypes are enriched in specific types of structural variations, which may underlay alternative mechanisms of genomic instability promoting cancer evolution.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4947. doi:1538-7445.AM2012-4947
Abstract 4954: The expression of X-linked inhibitor of apoptosis in human oral squamous cell carcinoma and its relationship with clinical factors
Authors: Tamatani Tetsuya , Takamaru Natsumi , Uchida Daisuke , Nagai Hirokazu , Fujisawa Kenji , Miyamoto Youji 
Published: August 2012

Abstract
[Background] X-linked inhibitor of apoptosis (XIAP) is a member of the inhibitor of apoptosis protein family, which is associated with cell survival by blocking caspase-mediated apoptosis. XIAP is expressed in various malignant tumors. The overexpression of XIAP has been reported to be a poorer prognostic factor in various malignancies. However, the prognostic value of XIAP expression in patients with oral cancer is not still cleared. [Purpose] The aims of present study were to evaluate the expression of XIAP protein in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the XIAP expression, clinical stages, histological differentiation and classification of invasion mode. [Materials and Methods] Four human OSCC cell lines, B88, CAL27, HNt, and HSC3 cells were used in this study. Normal gingival epithelial cells served as control. XIAP expression of cultured cells was detected by western blot. Tissue specimens were obtains from 85 patients with OSCC after surgery or biopsy. XIAP expression was detected by an immunohistochemical method. [Results] The expression of XIAP was detected in all cancer cells, but not in normal cells. Immunohistochemical analysis of 85 cases of OSCC showed that 73 (86%) cases expressed XIAP. There was no relationship between XIAP expression and clinical stages, or classification of invasion mode. There were significant differences between XIAP expression and histological differentiation. Most of non-staining and weakly staining of cancer was well differentiated. In contrast, intense and extensive staining was frequently found in poorly differentiated cancer. [Conclusions] These findings suggested that the expression of XIAP in OSCC could be related to histological differentiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4954. doi:1538-7445.AM2012-4954
Abstract 4964: Mutations of cysteine residues in Bcl-2 suppress hydrogen peroxide-induced apoptosis of human lung cancer cells through ERK1/2 interaction
Authors: Luanpitpong Sudjit , Wang Liying , Rojanasakul Yon 
Published: August 2012

Abstract
Bcl-2 is an essential antiapoptotic protein of the mitochondrial death pathway whose expression is highly associated with apoptosis resistance in cancer cells. Hydrogen peroxide is a signaling molecule mediating apoptosis to various stimuli, e.g. cisplatin and lipoic acid, in lung cancer cells. Direct treatment of the cells with hydrogen peroxide induced oxidative stress and a concomitant increase in apoptosis of human lung cancer H460 cells. Cysteine residues are likely targets of oxidative modifications of proteins; however, their effects on apoptosis and mechanisms of regulation are not known. To determine the role of cysteine residues, we constructed Bcl-2 mutant plasmids replacing the two cysteine residues Cys158 and Cys229 with alanines (Bcl-2-DM). Overexpression of Bcl-2-DM strongly suppressed the apoptosis induced by hydrogen peroxide in H460 cells as compared to that in control cells overexpressing wild-type Bcl-2. We further found that Bcl-2 directly interacts with MAP kinase ERK1/2 and that hydrogen peroxide disrupts such interaction. However, hydrogen peroxide treatment had a minimal effect on Bcl-2 and ERK1/2 interaction in Bcl-2-DM overexpressing cells, suggesting that Cys158 and Cys229 are required for the oxidative signaling. These findings identified a novel mechanism of oxidative regulation of apoptosis via cysteine modifications of Bcl-2.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4964. doi:1538-7445.AM2012-4964
Abstract 4966: The anti-apoptotic activity of caspase-2 short isoform is regulated by XPC protein
Authors: Wang Qi-En , Han Chunhua , Wani Altaf A. 
Published: August 2012

Abstract
Caspase-2 (casp-2) is the most conserved caspase across species. The casp-2 gene produces several alternative splicing isoforms. The inclusion of exon 9 leads to the inclusion of an in-frame stop codon in casp-2 short isoform (casp-2S) mRNA, thus producing a truncated protein that inhibits cell death, whereas the exclusion of exon 9 results in casp-2 long isoform (casp-2L) mRNA, whose protein product induces cell death. Earlier it has been reported that casp-2 is required for stress-induced apoptosis. However, that study could not have separated the roles of casp-2L and casp-2S, since the siRNA used in their experiments actually targeted both casp-2 isoforms. We have reported that targeted RNAi-mediated down-regulation of casp-2S enhanced the UV-induced apoptosis in XPC-deficient but not in XPC-proficient cells. However, by using the siRNA targeting both casp-2L and casp-2S, we failed to find any influence of casp-2 down-regulation on UV-induced apoptosis in these fibroblasts. Similarly, casp-2 specific inhibitor z-VDVAD was unable to reduce UV-induced apoptosis. In addition, the expression of casp-2S, but not casp-2L is regulated by XPC protein. To gain insight into the mechanism by which XPC down-regulates casp-2S, we examined the casp-2S promoter activity and the enrichment of XPC protein on casp-2S promoter. Our data clearly demonstrated that XPC protein can inhibit casp-2S promoter through binding to the promoter region. Furthermore, our cellular fractionation study demonstrated that casp-2L exclusively resides in cytoplasm, while casp-2S can be detected in both cytoplasm and nucleus. UV irradiation reduced the amount of nuclear casp-2S in XPC-proficient cells, while this reduction is not prominent in XPC-deficient cells, indicating that XPC protein facilitates the depletion of nuclear casp-2S upon UV irradiation. This finding provides an additional mechanism by which XPC facilitates DNA damage-induced apoptosis. (Supported by NIH grants CA151248 to QEW and ES12991 to AAW.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4966. doi:1538-7445.AM2012-4966
Abstract 4967: Altholactone induces caspase dependent and independent apoptosis of human colorectal cancer cells
Authors: Mhaidat Nizar M. 
Published: August 2012

Abstract
Resistance of colorectal cancer (CRC) to the available chemotherapy reveals the demand for identification of new anticancer agents. We evaluated the antitumor potential of altholactone, a naturally occurring bioactive compound isolated from Goniothalamus spp. (Annonaceae) hooks, against CRC cells. Antitumor activity of altholactone was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the propidium iodide method. Apoptosis mediators involved were assessed using biochemical inhibitors and Western blotting analysis. Results revealed that altholactone induced varying degrees of apoptosis in CRC cells but not in normal fibroblasts. Dissection of the altholactone-induced apoptotic signalling pathway revealed that altholactone activated caspase-dependent and -independent apoptotic pathways. Activation of caspase-4 appeared to be the initiating event in the caspase-dependent apoptotic pathway. Pre-treatment of CRC cells with the antioxidant N-acetylcysteine (NAC) significantly inhibited activation of caspase-4 and altholactone-induced apoptosis. These results indicate that altholactone induces selective cytotoxicity against colon carcinoma cells and warrants further clinical evaluation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4967. doi:1538-7445.AM2012-4967
Abstract 5042: A-AS1, a long non-protein coding RNA overexpressed in esophageal adenocarcinoma, influences cancer cell proliferation and apoptosis
Authors: Wu Wenjing , Song Jee Hoon , Cheng Yulan , Meltzer Stephen J. 
Published: August 2012

Abstract
Esophageal adenocarcinoma (EAC) is one of the fastest-growing cancers in the Western world. 95% of EACs occur without any antecedent diagnosis of Barrett's esophagus (BE). In these 95% of EAC patients, 5-year survival is only 15%. The rising incidence and poor prognosis of EAC have intensified research efforts into earlier methods to detect this disease. The majority of the human genome is transcribed and generates mostly non-coding (nc)RNAs that do not encode protein information. Long non-coding RNAs (lncRNAs) are emerging as a novel class of ncRNAs, but knowledge about these ncRNAs is limited. Recently, dysregulation of lncRNAs has been shown in various types of cancer, suggesting that lncRNAs may be involved in tumorigenesis or tumor progression. In the present study, we report that a number of lncRNAs are differentially expressed in EAC tissues and cell lines relative to normal esophageal tissues and cell lines. One of these lncRNAs, A-AS1 is derived from the antisense strand of the A gene locus and is overexpressed in EACs relative to matched normal esophagus (NE). Cell proliferation and colony formation assays revealed that A-AS1 siRNA-mediated knockdown reduces cell proliferation and colony-forming ability. In vitro scratch assays, migration and invasion assays in vitro also demonstrated decreased migration and invasion induced by A-AS1 siRNA knockdown. Moreover, we found that inhibition of A-AS1 expression results in increased apoptosis in EAC cell lines. Taken together, these results suggest that the elevated expression of A-AS1 observed in EACs may have contributed to their development or progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5042. doi:1538-7445.AM2012-5042
Abstract 5052: MicroRNA alterations following radiation in melanoma
Authors: Walston Steve A. , Gordon Nicolaus , Chakravarti Arnab , Palanichamy Kamalakannan 
Published: August 2012

Abstract
Purpose: Melanoma only accounts for 4% of skin cancer while causing 75% of cancer related deaths. Also, the incidence is increasing with the annual percent change in the United States reported as 2.4% for the period 1986-2006 and currently increasing faster than any other cancer worldwide. Moreover, patients who develop locally advanced or metastatic melanoma have limited treatment options with 5-year survival rates of 65% and 16%, for regional disease and metastatic disease, respectively. Historically, melanoma was regarded as resistant to radiation therapy (RT), however, recently the utility of RT has been re-explored in the adjuvant setting with fractionated radiotherapy (FRT) and also in the oligometastatic setting with stereotactic radiotherapy (SBRT), and does show increase in local control in appropriately selected patients. The importance of microRNA (miRNA) in cancer continues to be elucidated and in melanoma they are extensively reported as having significant roles in melanoma transformation, progression, invasiveness, metastasis, and outcome/prognosis. However, there are no reports of melanoma miRNA profiling and RT. miRNA expression profiles change as a consequence of RT in several tumor types. Experiments show delivery of miRNA in vivo appears both feasible and tolerable in murine models. Additionally, correcting miRNA deregulation has been shown to mitigate the tumorigenic phenotype and also induce radiosensitivity in vitro and in vivo. Materials/Methods: We cultured more than a dozen melanoma cell lines and sequenced for mutations in key genes such as B-RAF, N-RAS, etc. to group them. Next we isolated their miRNA of untreated and treated with 6 Gray dose of radiation isolated at 5 days. The miRNA expression was quantified using RT-qPCR of TaqMan Low Density Arrays (TLDA) cards. The data is reported using hierarchical clustering and those miRNAs significantly deregulated have been delineated. Results/Discussion: We have characterized the miRNA expression profiles of melanoma cell lines when comparing untreated and those treated with radiation. Our data indicate that miRNA profiles done pre and post RT are significantly different. To this end we have identified clusters of miRNA associated with RT sensitivity/resistance. Thus, these miRNAs could be important factors in response to RT and their differential expression may be linked to resistance to RT. Consequently, it is conceivable that these miRNA and/or their mRNA targets could be used in the future as targets for drug development to radiosensitize melanoma and thus further improve outcomes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5052. doi:1538-7445.AM2012-5052