bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2490: Novel application for pseudopodial proteomics using excimer laserablation and two-dimensional difference gel electrophoresis.
Authors: Mimae Takahiro , Ito Akihiko , Hagiyama Man , Kondo Tadashi , Okada Morihito 
Published: August 2014

Abstract
We developed a novel application to conduct pseudopodia proteomics. Pseudopodia are ventral actin-rich protrusions and play functional roles in cell migrations. Identification of pseudopodia proteins leads further understanding of malignant phenotypes of tumor cells and novel therapeutic strategies. In our application, tumor cells were placed on a fibronectin-coated porous membrane to form pseudopodia. According to the motile potentials of the cells, the cells formed pseudopodial microprocesses in the pores. An excimer laser, which was used for ophthalmic refractive surgeries, horizontally ablated cells at the membrane surface to remove the cell body. The microscopic observations and the protein expression studies suggested that the laser treatment caused no apparent damages to pseudopodia. Proteins in whole cells and pseudopodia fractions were individually solubilized, labeled with a highly sensitive fluorescent dye, and separated using two-dimensional difference gel electrophoresis. Among 2508 protein spots observed, 211 had different intensity between whole cells and pseudopodia fractions (more than 4-fold differences and p value less than 0.05). The protein enrichment depended on the pore size. Mass spectrometric protein identification revealed 46 pseudopodia-localizing proteins. The localization of novel pseudopodia-localizing proteins such as RAB1A, HSP90B, TDRD7, and vimentin was confirmed using immunohistochemical examinations. The previous studies demonstrated that these four proteins may function in the cell migration process. In addition, RAB1A was indicated to play an important role in forming and extending pseudopodial microprocesses in human breast cancer cells by overexpression and knockdown experiments. This method will provide insights into the molecular details of pseudopodia and further understanding of malignant phenotypes of tumor cells and novel therapeutic strategies.
Citation Format: Takahiro Mimae, Akihiko Ito, Man Hagiyama, Tadashi Kondo, Morihito Okada. Novel application for pseudopodial proteomics using excimer laserablation and two-dimensional difference gel electrophoresis. [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 2490. doi:10.1158/1538-7445.AM2013-2490
Abstract 2492: Targeted quantitation of candidate metabolic biomarkers for hepatocellular carcinoma.
Authors: Xiao Jun Feng , Zhao Yi , Varghese Rency , Zhou Bin , Poto Cristina Di , Zhang Lihua , Tadesse Mahlet G. , Ziada Dina Hazem , Shetty Kirti , Ressom Habtom W. 
Published: August 2014

Abstract
The aim of this study is to compare metabolite levels in sera of hepatocellular carcinoma (HCC) patients versus cirrhotic controls. This is accomplished through targeted quantitative analysis of candidate metabolic biomarkers of HCC by using an ultra-performance liquid chromatography coupled to an electrospray ionization-quadrupole linear ion trap mass spectrometry (UPLC-ESI-QLIT MS). The targets were selected from our previous untargeted analysis, where we observed association of HCC to dysregulated levels of bile acids, lysophosphocholines (LPCs), lysophosphoethanolamines (LPEs), sphingophoslipid, long chain carnitines and amino acids. In this study, we performed quantitative analysis of three metabolites (glycodeoxycholic acid, 3beta 6beta-dihydroxy-5beta-cholan-24-oic acid, 3 sulfo-glycodeoxycholic acid) in sera of 199 participants from two cohorts (US and Egypt). The participants consist of 110 subjects (55 HCC cases and 55 cirrhotic controls) from the US and 89 subjects (40 HCC cases and 49 cirrhotic controls) from Egypt. Through a logistic regression model, we analyzed the quantitative results obtained by the UPLC-ESI-QLIT MS to evaluate the ability of the three candidate markers as a panel in distinguishing HCC cases from patients with liver cirrhosis. Receiver operating characteristic (ROC) curve obtained through the regression model yielded an area under the curve (AUC) of 0.754 in distinguishing the HCC cases from cirrhotic controls for the US cohort and an AUC of 0.709 for the Egyptian cohort. The model resulted in an AUC of 0.717 for the combined US and Egyptian cohort. We compared the diagnostic capability of these metabolites versus α-fetoprotein (AFP) in the US cohort, for which AFP measurements were available for both the HCC cases and cirrhotic controls. While AFP alone resulted in an AUC of 0.681, the combination of AFP with the three metabolites increased the AUC to 0.806. These results indicate the potential of these candidate biomarkers in combination with AFP for more accurate diagnosis of HCC in high risk population of cirrhotic patients.
Citation Format: Jun Feng Xiao, Yi Zhao, Rency Varghese, Bin Zhou, Cristina Di Poto, Lihua Zhang, Mahlet G. Tadesse, Dina Hazem Ziada, Kirti Shetty, Habtom W. Ressom. Targeted quantitation of candidate metabolic biomarkers for hepatocellular carcinoma. [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 2492. doi:10.1158/1538-7445.AM2013-2492
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2499: Diagnostic serum biomarkers for canine hemangiosarcoma: a potential model of human angiosarcoma.
Authors: Choi Eunju , Chen David , Lê Cao Kim-Anh , Bielefeldt-Ohmann Helle , O'Leary Caroline A. , Hill Michelle M. 
Published: August 2014

Abstract
People suffering from uncommon diseases often do not benefit from the advances in medical research due to lack of research. One such disease is angiosarcoma, a highly aggressive cancer originating from blood vessels with risk factors including toxic exposure, radiotherapy and lymphedema. Angiosarcoma in dogs (commonly called hemangiosarcoma) is a very similar disease with much higher prevalence, comprising up to 7% of all canine malignancies. For both species, an accurate diagnostic method is needed for more favorable outcome.
We developed a biomarker discovery pipeline consisting of a high-throughput biomarker discovery platform and a database for data mining and statistical analysis for candidate identification. The platform screens for differential glycosylation of serum glycoproteins as potential biomarkers utilizing 20 individual lectins followed by direct coupling to tandem mass spectrometry. The database facilitates the identification of differential glycosylation and produces a ranked list of potential biomarker candidates. Using this pipeline, sera from 10 dogs with hemangiosarcoma with 10 age and sex-matched control sera were processed and analyzed.
Candidates from the database were ranked based on its ability to classify normal and cancer. The ranked list of candidates for this screen composed of glycoproteins involved in cell migration, tumor immune response, and glycoproteins reported to be altered in human and canine angiosarcoma and other cancer types. Some examples will be shown to illustrate the change in specific glycosylation structures associated with cancer as measured by binding to specific lectin(s) while binding to other lectins are not changed. These glycosylation-specific changes are potentially more specific diagnostic biomarkers than circulating proteins alone.
We are currently validating the identified candidates and pursuing the development of clinical tests to improve diagnosis and clinical outcomes of angiosarcoma for both dogs and humans.
Citation Format: Eunju Choi, David Chen, Kim-Anh Lê Cao, Helle Bielefeldt-Ohmann, Caroline A. O'Leary, Michelle M. Hill. Diagnostic serum biomarkers for canine hemangiosarcoma: a potential model of human angiosarcoma. [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 2499. doi:10.1158/1538-7445.AM2013-2499
Abstract 2506: Histology-directed lipid MALDI MS profiling can distinguish prostate cancer from normal epithelium.
Authors: Choi Seungho , Park Jun Won , Park Weon Seo , Kim Hark Kyun , Lee Kang Hyun 
Published: August 2014

Abstract
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is demonstrated to be useful for profiling of common solid tumors. In this approach, mass spectra are obtained from discrete locations on 10 μm-thick cryosection tissue, guided by H&E-stained top slide. To determine if a lipid signature obtained from tissue samples could be found to assist with diagnosis, frozen surgical samples collected from 7 prostate cancer patients and 9 adjacent normal tissue samples were analyzed using matrix (DHB/CHCA)-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). When leave-one-out cross validation was performed using support vector machine, permutation p value for the cross-validated misclassification rate was statistically significant (p=0.04), suggesting that lipid profiles are clearly different between prostate cancer and adjacent normal tissue samples. One of the most striking difference between prostate cancer and normal tissue is the phosphatidylcholine (PC) 32:1 (m/z 798.6) overexpression (p=0.007, tumor/normal=2.4). In order to identify molecular mechanisms of PC 32:1 overexpression in prostate cancers, we performed immunohistochemical analyses for metabolic enzymes responsible for phosphatidylcholine biosynthesis. Prostate cancers overexpress choline kinases and phosphate cytidylyltransferases, known oncogenes which generate phosphatidylcholines, compared with adjacent normal tissue samples. Thus, lipid MALDI MS analysis captures a global alteration in lipid profile of prostate cancer tissue, potentially distinguishing cancerous epithelium from normal epithelium. To our knowledge, this study is the first comprehensive lipid profiling study in prostate cancer. This histology-directed MALDI MS approach enables rapid and sensitive identification of discriminatory lipids in cancerous epithelium of prostate cancers, even those with infiltrative growth.
We are in the process of a large sample set (Supported by Korean Ministry of Education, Science, and Technology Grant 2012K001506).
Citation Format: Seungho Choi, Jun Won Park, Weon Seo Park, Hark Kyun Kim, Kang Hyun Lee. Histology-directed lipid MALDI MS profiling can distinguish prostate cancer from normal epithelium. [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 2506. doi:10.1158/1538-7445.AM2013-2506
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2542: Evidence for large somatic structural events detected as autosomal genetic mosaicism in GWAS data.
Authors: Machiela Mitchell J. , Zhou Weiyin , Yeager Meredith , Jacobs Kevin , Berndt Sonja , Lan Qing , Rothman Nathaniel , Savage Sharon , Taylor Phil R. , deVivo Immaculata ,   National Cancer Institute Detectable Clonal Mosaicism Consortium, Hoover Robert N. , Tucker Margaret A. , Chanock Stephen J. 
Published: August 2014

Abstract
Recent evidence indicates human mosaic abnormalities may be more common than previously expected. We performed an analysis on blood and buccal DNA of 30,918 individuals from a collection of 54 cancer-related studies using a modified mosaic alteration detection algorithm on renormalized B-allele frequencies and log2 relative probe intensity ratios from commercially available Illumina SNP microarray chips. 391 autosomal abnormalities &gt;2Mb in size were detected in 232 (0.75%) individuals. The distribution includes copy-neutral loss of heterozygosity constituting 192 (49%) events, copy gains 85 (22%) events, and copy losses 102 (26%) events. There was no difference between blood and buccal sources of DNA. An overall analysis by age confirmed our earlier finding (p=8.93e-07), which was also observed in controls (p=0.0086). Similarly, an overall analysis by sex confirmed mosaic abnormalities are more frequent in males than females (p=0.0016); and this association was also observed in a control-only analysis (p=0.0019). Two or more distinct autosomal events were observed in 43 individuals. Comparable to earlier studies, the most common events were 4q copy neutral loss of heterozygosity, 9q copy neutral loss of heterozygosity, 13q14 deletion and 20q deletion. 13q14 deletion was observed in cancer-free controls and individuals with epithelial cancers. Cancer specific analyses for bladder, endometrium, stomach, lung (in nonsmoking women from Asia), osteosarcoma, and prostate cancer revealed no significant association with risk for cancer. These results replicate the prevalence and age/sex relationships from our previous findings in an analysis of 57,853 individuals and further suggest the importance of studying mosaic abnormalities in the general human population. The findings underscore the importance of thorough characterization of germline DNA in parallel with somatic characterization. Our results provide further support for age-related genomic senescence and could represent the tip of the iceberg for smaller somatic events.
Citation Format: Mitchell J. Machiela, Weiyin Zhou, Meredith Yeager, Kevin Jacobs, Sonja Berndt, Qing Lan, Nathaniel Rothman, Sharon Savage, Phil R. Taylor, Immaculata deVivo, National Cancer Institute Detectable Clonal Mosaicism Consortium, Robert N. Hoover, Margaret A. Tucker, Stephen J. Chanock. Evidence for large somatic structural events detected as autosomal genetic mosaicism in GWAS data. [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 2542. doi:10.1158/1538-7445.AM2013-2542
Abstract 2546: Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression.
Authors: Kote-Jarai Zsofia , Saunders Edward , Leongamornlert Daniel , Tymrakiewicz Malgorzata , Dadaev Tokhir , Jugurnauth Sarah , Benlloch Sara , Amin Al Olama Ali , Ross-Adams Helen , Neal David ,   The UKGPCS Collaborators and The PRACTICAL Consortium, Douglas Easton, Eeles Rosalind 
Published: August 2014

Abstract
We have previously reported an association between prostate cancer (PrCa) risk and rs2242652 on 5p15. rs2242652 lies in intron 4 of TERT, which encodes telomerase reverse transcriptase, the catalytic subunit of the telomerase ribonucleoprotein complex. Telomerase catalyzes the de novo addition of telomere repeat sequences on to chromosome ends and thereby counterbalances telomere-dependent replicative senescence. Associations between SNPs in the TERT region and multiple cancer types have been reported; however no correlation has been observed thus far between the cancer-associated SNPs in TERT and gene expression or telomere length. To comprehensively evaluate the association between genetic variation across this region and PrCa we performed a fine-mapping analysis by direct genotyping using either a custom Illumina iSelect array (114 SNPs on iCOGS) or Sequenom MassArray iPlex (25 SNPs) followed by imputation of 1,094 SNPs in 22,301 PrCa cases and 22,320 controls in the PRACTICAL consortium. To determine independently associated variants in this region, we performed multiple stepwise logistic regression analysis; SNPs were included in the model if they were significant at P&lt;10−4 after adjustment for other SNPs. Regression models identified multiple independent associations, reflecting the complexity of this region. These SNPs fall into four regions consisting of clusters of highly or moderately correlated variants, and there is only weak LD between SNPs in different regions. To investigate whether SNPs in any of these regions were associated with TERT gene expression, we performed qPCR assays on RNA from benign prostate tissue samples using the Fluidigm Biomark™ HD system. We found evidence that the risk reducing alleles of several variants in region one associated with elevated TERT expression, providing a plausible mechanism for the differential effect of SNPs on PrCa risk. Deep re-sequencing of these loci may help to further refine this region and facilitate selection of prospective causal variants for functional validation studies.
Citation Format: Zsofia Kote-Jarai, Edward Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Tokhir Dadaev, Sarah Jugurnauth, Sara Benlloch, Ali Amin Al Olama, Helen Ross-Adams, David Neal, The UKGPCS Collaborators and The PRACTICAL Consortium, Douglas Easton, Rosalind Eeles. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. [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 2546. doi:10.1158/1538-7445.AM2013-2546
Abstract 2548: Targeted sequencing to identify rare variants in colorectal cancer.
Authors: DeRycke Melissa S. , Gunawardena Shanaka R. , Middha Sumit , McDonnell Shannon K. , Riska Shaun M. , Fogarty Zachary C. , Eckloff Bruce W. , Schaid Daniel J. , Goode Ellen L. , Thibodeau Stephen N. 
Published: August 2014

Abstract
Colorectal cancer (CRC) is estimated to be the third most common cancer in both men and women in the US in 2012, accounting for over 50,000 deaths. Familial CRC accounts for approximately 30% of all CRC, yet only 5% of familial CRCs can be attributed to mutations in known hereditary colon cancer (HCC) genes. Many families with a strong family history of CRC do not have mutations in known CRC genes. Finding the genes underpinning CRC in these families may improve screening for disease and allow the development of more targeted therapeutics.
We completed targeted sequencing of over 2,000 genes and miRNAs in 1,500 cases of CRC from the Colon Cancer Family Registry (CCFR) in an effort to identify rare variants associated with CRC risk and to identify mutations in known CRC genes missed by conventional sequencing. Several categories of genes were included: 18 known HCC genes; 18 candidate HCC genes; 185 genes in previously reported CRC linkage peaks; 1,423 miRNAs; and 363 genes identified through whole exome sequencing of 40 affected cases in 16 families with hereditary CRC (n=2,007 total genes sequenced). Genomic DNA samples were indexed, then libraries were made using Agilent's SureSelect Targeted Enrichment kit. Samples were pooled (96 samples/pool), then each pool of samples was run on five lanes on an Illumina HiSeq2000 (average of 19.2 samples/lane). GenomeGPS, an in-house developed workflow, was used for read alignment, variant calling, and annotation.
In early analyses of the first 161 cases, the mean number of mapped reads exceeded 20 million per sample and over 90% of the target region exceeded 40x coverage. A total of 26,484 SNPs were identified and passed quality filtering. Sequencing identified known mutations in MMR genes in positive control cases as well as mutations in HCC genes in previously untested cases. Analysis is currently on-going on the remaining samples and we will report results on the full set of 1500 cases at the meeting.
Citation Format: Melissa S. DeRycke, Shanaka R. Gunawardena, Sumit Middha, Shannon K. McDonnell, Shaun M. Riska, Zachary C. Fogarty, Bruce W. Eckloff, Daniel J. Schaid, Ellen L. Goode, Stephen N. Thibodeau. Targeted sequencing to identify rare variants in colorectal cancer. [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 2548. doi:10.1158/1538-7445.AM2013-2548
Abstract 2549: A genome-wide association study identifies PSCA as a susceptibility locus for gastric cancer and duodenal ulcer in the Japanese population.
Authors: Tanikawa Chizu , Matsuda Koichi , Nakamura Yusuke 
Published: August 2014

Abstract
Through a genome-wide association analysis using a total of 7,035 duodenal ulcer cases and 25,323 controls of Japanese populations, we identified two susceptibility loci at the Prostate stem cell antigen (PSCA) on 8q24 and at the ABO blood group (ABO) on 9q34. A C-allele of rs2294008 at PSCA increased the risk of duodenal ulcer (odds ratio (OR) of 1.84 with P value of 3.92 x 10-33) in a recessive model, while it decreased the risk of gastric cancer (OR of 0.79 with P value of 6.79 x 10-12) as reported previously. A T-allele of SNP rs2294008 created the upstream translational initiation codon and affects the protein localization from cytoplasm to cell surface. SNP rs505922 on ABO also associated with duodenal ulcer in a recessive model (OR of 1.32 with P value of 1.15 x 10-10). Our finding implies the crucial roles of genetic variations on the pathogenesis of duodenal ulcer.
Citation Format: Chizu Tanikawa, Koichi Matsuda, Yusuke Nakamura. A genome-wide association study identifies PSCA as a susceptibility locus for gastric cancer and duodenal ulcer in the Japanese population. [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 2549. doi:10.1158/1538-7445.AM2013-2549
Abstract 2551: A genome-wide association study of HCV induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at MHC region.
Authors: Koichi Matsuda , Tanikawa Chizu , Nakamura Yusuke 
Published: August 2014

Abstract
To identify a prognostic factor(s) for patients with chronic hepatitis C (CHC), we conducted a genome-wide association study (GWAS) using 682 hepatitis C virus (HCV)-induced liver cirrhosis (LC) cases and 1,045 CHC patients in Japan. Eight SNPs which showed possible associations (P &lt; 1.0 x 10-5) in the GWAS stage were further genotyped using 936 LC cases and 3,809 CHC patients. We found that two SNPs within the major histocompatibility complex (MHC) region on chromosome 6p21, rs910049 and rs3135363, were significantly associated with the progression from CHC to LC (Pcombined = 9.15 x 10-11 and 1.45 x 10-10, odds ratio (OR) = 1.46 and 1.37, respectively). We also found that HLA-DQA1*0601 and HLA-DRB1*0405 were associated with progression from CHC to LC (P = 4.53 x 10-4 and 1.54 x 10-4 with OR = 2.80 and 1.45, respectively). Multiple logistic regression analysis revealed that rs3135363, rs910049, and HLA-DQA1*0601 were independently associated with the risk of HCV-induced LC. In addition, individuals with four or more risk alleles for these three loci have a 2.83-fold higher risk for LC than those with no risk allele, indicating the cumulative effects of these variations. Our findings elucidated the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients.
Citation Format: Matsuda Koichi, Chizu Tanikawa, Yusuke Nakamura. A genome-wide association study of HCV induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at MHC region. [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 2551. doi:10.1158/1538-7445.AM2013-2551