bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 113: Gamma-H2AX level in peripheral blood lymphocytes as a risk predictor for bladder cancer.
Authors: Fernandez Mario I. , Gong Yilei , Ye Yuanqing , Lin Jie , Chang David , Wu Xifeng 
Published: August 2014

Abstract
Introduction: Identification of susceptibility to double-strand breaks (DSB) may provide valuable information about genomic instability and cancer risk. The formation of gamma-H2AX foci is a highly sensitive marker for DNA DSBs induction. We assessed whether levels of gamma-H2AX in peripheral blood lymphocytes (PBL) obtained after stimulation by ionizing radiation (IR) are associated with bladder cancer risk in a bladder cancer case-control study.
Material and Methods: Patients and controls were enrolled from an ongoing bladder cancer case-control study. Epidemiologic data were collected during an in-person interview using a structured questionnaire. Baseline and IR induced H2AX-phosphorylation was assessed in PBL from 174 newly diagnosed, previously untreated bladder cancer patients and from 174 age, sex and ethnicity matched, healthy control subjects by a novel, image-based, high-throughput phenotypic assay. The ratio of gamma-H2AX level of IR-treated cells to that of non-treated cells (baseline) derived from the same blood sample was used as the parameter to assess the sensitivity to the mutagen. Logistic regression analysis was used to estimate odds ratios associated with gamma-H2AX. We also compared the discriminatory ability of a model with only demographic variables and a model including gamma-H2AX ratio.
Results: The mean gamma-H2AX ratios were significantly higher for cases than for controls (1.43±0.14 vs. 1.35±0.12; p=1.44E-08). This trend was irrespective of age, sex or smoking status. The risk estimates of bladder cancer for induced DNA DSBs showed a significant trend for increased risk at the highest tertiles for the whole cohort (OR=3.09; 95%CI 1.76-5.40; p=8.15E-05 for the second tertile and OR=3.78; 95%CI 2.26-6.33; p=4.18E-07 for the third tertile) as well as for each category. Discrimination ability of the epidemiological model was moderate, with an area under curve (AUC) of 0.64. However, the AUC increased significantly to 0.74 when gamma-H2AX ratio was incorporated.
Conclusions: Our findings suggest that a higher susceptibility to induction of DSBs as measured by the gamma-H2AX assay is significantly associated with an increased risk for bladder cancer. This might help to identify individuals at high risk for this cancer, adding new perspectives to established epidemiological and genetic risk factors. Further research of the role of gamma-H2AX in biological processes of bladder cancer is warranted.
Citation Format: Mario I. Fernandez, Yilei Gong, Yuanqing Ye, Jie Lin, David Chang, Xifeng Wu. Gamma-H2AX level in peripheral blood lymphocytes as a risk predictor for bladder 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 113. doi:10.1158/1538-7445.AM2013-113
Abstract 1158: Detection of clonally expanded HBV DNA integration sites as a marker for early detection of HBV related HCC.
Authors: Lin Selena , Jain Surbhi , Block Timothy , Song Frank , Su Ying Hsiu 
Published: August 2014

Abstract
Hepatocellular carcinoma (HCC), the 5th most frequent cancer worldwide, has a 5-year survival rate of 14% because it is difficult to diagnose at its curative stages. The goal of this project is to determine if the detection of clonally expanded HBV DNA integration sites can be used as a marker for early detection of HBV related HCC (HBV-HCC) in order to improve its prognosis
Hepatitis B virus (HBV) infections are associated with over 80% of HCC cases worldwide. Upon infection, the HBV genome integrates into the host chromosome at a random site, thus creating a unique genetic signature for each HBV infected cell. Certain HBV infected cells undergo progressive “uncontrolled clonal expansion” leading to the development of tumors, resulting in an over expansion of the unique HBV integration sites making them the predominant or “major HBV integration sites” (MIS).
Cell-free circulating DNA from cancer patients reflects the characteristics of the tumor DNA. We and others have shown that urine contains DNA from the circulation and can be used as a source for cell-free circulating DNA. Successful detection of HBV integration sites in the circulation of HBV-HCC patients has not been demonstrated. In order to detect cell free circulating HBV DNA integration sites, a targeted enriched Next Generation Sequencing (NGS) assay was developed. Targeted enrichment was performed using an in-solution hybridization platform with biotinylated HBV RNA baits surrounding the HBV DNA nucleotide positions 1571 to 1960, the most frequent HBV breakpoint region. The assay was tested using library constructed DNA controls: Hep3B, which contains integrated DNA, and HepG2, which contains no HBV DNA. To determine the amount of captured DNA containing HBV DNA, the captured DNA was quantified for HBV containing DNA and total captured DNA. Almost all captured DNA contained HBV DNA. To confirm targeted capture of integrated HBV DNA, the captured DNA was cloned followed by sequencing. 3 out of 3 clones that were sequenced contain integrated HBV DNA. This assay demonstrated targeted capture and enrichment of HBV integration sites. This assay will be tested for sensitivity in detecting HBV integration sites and used to establish the criteria for the appearance of MIS as a biomarker for HBV-HCC. Overall, if successful, this cancer related HBV DNA marker would offer a high specificity and sensitivity in screening for HBV-HCC.
Citation Format: Selena Lin, Surbhi Jain, Timothy Block, Frank Song, Ying Hsiu Su. Detection of clonally expanded HBV DNA integration sites as a marker for early detection of HBV related HCC. [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 1158. doi:10.1158/1538-7445.AM2013-1158
Abstract 1200: Molecular subtypes of gastric cancer show systematic differences in response to PI3K inhibitors and fluorouracil.
Authors: Lei Zengdeng , Deng Nian Tao , Zouridis Hermioni , Tan Iain Beehaut , Ooi Chia Huey , Ivanova Tatiana , Zhang Shenli , Lee Minghui , Wu Jeanie , Ngo Anna , Manesh Sravanthy , Boussioutas Alex , Teh Bin Tean , Goh Liang Kee , Flotow Horst , Tan Patrick , Rozen Steven G. 
Published: August 2014

Abstract
Background & Aims: Gastric cancer is the second leading cause of cancer death worldwide, killing &gt;730,000 people every year. Almost all gastric cancers are adenocarcinomas, which exhibit considerable heterogeneity between patients. We sought to identify subtypes of gastric adenocarcinomas that have particular biological properties and responses to cytotoxic drugs. Methods: Robust unsupervised clustering of 248 gastric tumors based on global gene expression revealed three major subtypes. We developed a classifier, GC-Class ("Gastric Cancer Classifier") for the three subtypes and validated it in a second set of 70 tumors. We then determined the distinct genomic and epigenomic properties and drug sensitivities of the subtypes. We determined drug sensitivities of primary tumors by multivariate Cox proportional hazard modeling using clinical survival data. We determined drug sensitivities in cell lines using previously reported data and high-throughput screening of 158 compounds in 23 gastric cancer cell lines. Results: There are three major subtypes of gastric adenocarcinoma: “invasive," “proliferative," and “metabolic”. The subtypes show systematic differences in genomic and epigenetic characteristics and in drug response. Proliferative-subtype tumors show high genomic instability and DNA hypomethylation. Metabolic-subtype cancer cell lines are preferentially sensitive to fluorouracil, and, in two independent groups, patients with the metabolic-subtype tumors benefited significantly from fluorouracil treatment. Invasive-subtype tumors have characteristics in common with cancer stem cells, and cell lines in this subtype are particularly sensitive to PI3K/AKT/mTOR inhibitors. Conclusions: The molecular classification of gastric cancers reported here is reproducible and biologically and therapeutically meaningful, and it holds promise as a basis for selecting and developing therapies tailored to particular subtypes.
Citation Format: Zengdeng Lei, Nian Tao Deng, Hermioni Zouridis, Iain Beehaut Tan, Chia Huey Ooi, Tatiana Ivanova, Shenli Zhang, Minghui Lee, Jeanie Wu, Anna Ngo, Sravanthy Manesh, Alex Boussioutas, Bin Tean Teh, Liang Kee Goh, Horst Flotow, Patrick Tan, Steven G. Rozen. Molecular subtypes of gastric cancer show systematic differences in response to PI3K inhibitors and fluorouracil. [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 1200. doi:10.1158/1538-7445.AM2013-1200
Abstract 1277: Utilizing uterine cancer models to study malignant transformation driven by Lkb1 loss.
Authors: Peña Christopher G. , Nakada Yuji , Castrillon Diego 
Published: August 2014

Abstract
The serine-threonine kinase LKB1 is an upstream component of the AMPK-mTOR pathway and regulates cell survival and growth. Inherited germline mutations in LKB1 predispose women to endocervical malignancies whereas somatic mutations in LKB1 promote cervical cancer progression. Our lab has shown that tissue specific knockout of Lkb1 in the endometrial epithelium of mice facilitates growth of highly invasive, lethal tumors that are well differentiated and retain structural polarity. Additionally, stable shRNA mediated knockdown of LKB1 in human immortalized endocervical cells drives anchorage-independent growth. To investigate potential pathways involved in LKB1 mediated oncogenic transformation, we have employed a microarray based approach comparing hits from human immortalized endocervical cell lines and mouse tissue to identify specific genes that are differentially regulated when LKB1 function is absent. Preliminary data suggests that pro-angiogenic and inflammatory mediators are upregulated in LKB1 deficient cells. We are currently assessing the overall contribution of these factors to growth and invasiveness in our model systems and the mechanisms by which Lkb1 loss facilitates their activation. These pathways can be potential therapeutic targets in other cancers characterized by Lkb1 loss of function mutations.
Citation Format: Christopher G. Peña, Yuji Nakada, Diego Castrillon. Utilizing uterine cancer models to study malignant transformation driven by Lkb1 loss. [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 1277. doi:10.1158/1538-7445.AM2013-1277
Abstract 1292: β-catenin is activated in arsenic-transformed human bronchialepithelial cells and promotes angiogenesis .
Authors: Wang Zhishan , Humphries Brock , Yang Chengfeng 
Published: August 2014

Abstract
Arsenic exposure represents a major health concern causing human cancers, yet the mechanism of arsenic carcinogenesis has not been elucidated. We and others recently reported that cell malignant transformation by arsenic is accompanied by epithelial to mesenchymal transition (EMT). However, the role of EMT in arsenic carcinogenesis is not well understood. Although previous studies showed that acute short term arsenic treatment stimulates angiogenesis, it remains to be determined whether cells that were malignantly transformed by long term arsenic exposure have a pro-angiogenic effect. The objective of this study was to investigate the effect of arsenic-transformed human bronchial epithelial cells that underwent EMT on angiogenesis and the underlying mechanism. It was found that the conditioned medium from arsenic-transformed cells strongly stimulated tube formation by human umbilical vein endothelial cells (HUVECs). Moreover, enhanced angiogenesis was detected in mouse xenograft tumor tissues resulting from inoculation of arsenic-transformed cells. Mechanistic studies revealed that β-catenin was activated in arsenic-transformed cells up-regulating its target gene expression including angiogenic-stimulating vascular endothelial growth factor (VEGF). Stably expressing microRNA-200b in arsenic-transformed cells that reversed EMT inhibited β-catenin activation, decreased VEGF expression and reduced tube formation by HUVECs. SiRNA knocking down β-catenin decreased VEGF expression. Adding a VEGF neutralizing antibody into the conditioned medium from arsenic-transformed cells impaired tube formation by HUVECs. It was further determined that the canonical Wnt signaling was not increased in arsenic-transformed cells. These findings suggest that EMT in arsenic-transformed cells promotes angiogenesis through activating β-catenin-VEGF pathway in the absence of elevated-canonical Wnt signaling.
Citation Format: Zhishan Wang, Brock Humphries, Chengfeng Yang. β-catenin is activated in arsenic-transformed human bronchialepithelial cells and promotes angiogenesis . [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 1292. doi:10.1158/1538-7445.AM2013-1292
Abstract 1295: Inhibition of clonogenicity and xenograft tumor growth by activation and/or over-expression of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ).
Authors: Yao Pei-Li , Borland Michael G. , Krishnan Prasad , Zhu Bokai , Gonzalez Frank J. , Peters Jeffrey M. 
Published: August 2014

Abstract
The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) regulates a variety of biological processes but the function of PPARβ/δ in carcinogenesis remains controversial. Stable human cancer cell lines (A431, MDA-MB-231 and MCF7) that constitutively over-express PPARβ/δ were produced to effectively examine the role of this receptor in human cancer models. Ligand activation of PPARβ/δ both in MDA-MB-231 (ER-negative) and MCF7 (ER-positive) cells over-expressing PPARβ/δ cells caused significantly decreased clonogenicity compared to controls. Over-expression of PPARβ/δ reduced tumor volumes and tumor weights of ectopic xenografts from both MDA-MB-231 and MCF7cells compared to controls. Ligand activation of PPARβ/δ caused an even greater reduction of tumor volumes and tumor weights compared to controls. Interestingly, similar results were observed in the human epidermoid carcinoma cell line A431 and other human cancer cell lines. Ligand activation of PPARβ/δ strongly inhibited clonogenicity in A431 cells over-expressing PPARβ/δ. Xenografts from A431 control cells rapidly developed tumors while tumors were barely detectable in A431 cells over-expressing PPARβ/δ. These observations demonstrate the inhibitory effect of activating or over-expressing PPARβ/δ on tumorigenesis in human cancer cell lines. This suggests that PPARβ/δ suppression of tumorigenicity may be mediated through common mechanisms.
Citation Format: Pei-Li Yao, Michael G. Borland, Prasad Krishnan, Bokai Zhu, Frank J. Gonzalez, Jeffrey M. Peters. Inhibition of clonogenicity and xenograft tumor growth by activation and/or over-expression of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ). [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 1295. doi:10.1158/1538-7445.AM2013-1295
Abstract 1339: Mitochondrial DNA copy number is prospectively associated with breast cancer risk.
Authors: Thyagarajan Bharat , Wang Renwei , Barcelo Helene , Nelson Heather , Koh Woon Puay , Yuan Jian Min 
Published: August 2014

Abstract
A previous case-control study reported a positive association between mitochondrial DNA (mtDNA) copy number in peripheral blood and breast cancer risk. However, data on mtDNA copy number and breast cancer risk in prospective cohorts is lacking. We evaluated the prospective association between mtDNA copy number and breast cancer risk in the Singapore Chinese Health Study. We conducted a nested case-control study of 183 incident breast cancer cases with pre-diagnostic blood samples and 529 individually matched control women who were free of breast cancer. The mtDNA copy number was measured using real time PCR. Conditional logistic regression methods were employed to examine the association between mtDNA copy number and breast cancer risk. Overall, there was no association between mtDNA copy number and breast cancer after adjustment for potential confounders (p=0.37). Among participants who donated a blood sample within 3 years of breast cancer diagnosis women in the second and third tertile of mtDNA copy number had a significantly increased breast cancer risk as compared to those in the lowest mtDNA copy number tertile (odds ratio (95% confidence interval): 1.84 (0.93-3.64) and 2.13 (1.09-4.17) respectively; p for trend = 0.03). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥ 3 years before breast cancer diagnosis (p for trend = 0.73). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis.
Citation Format: Bharat Thyagarajan, Renwei Wang, Helene Barcelo, Heather Nelson, Woon Puay Koh, Jian Min Yuan. Mitochondrial DNA copy number is prospectively associated with breast cancer risk. [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 1339. doi:10.1158/1538-7445.AM2013-1339
Abstract 1341: Identification of significant linkage evidence for lethal prostate cancer on chromosome arm 11p15.
Authors: Cannon-Albright Lisa A. , Teerlink Craig C. , Agarwal Neeraj 
Published: August 2014

Abstract
We performed genome wide linkage analysis in a set of high-risk prostate cancer pedigrees, each with 3 or more sampled cases whose death certificate indicated a contribution of prostate cancer to death (lethal prostate cancer). All prostate cancer cases were present in the Utah SEER Cancer Registry (pathology confirmed); all “lethal” prostate cancer cases were also required to have a Utah death certificate indicating prostate cancer as a contributing cause of death.
A set of markers with no linkage disequilibrium was selected for linkage analysis. We took the intersection of SNP markers from five Illumina genotyping platforms used (550K, 610K, 1M,Omni_express (720k), and Omni_1M), resulting in selection of 301,646 markers. We began with the first marker on each chromosome and then skipped markers until one satisfied all criteria (min 0.1 cM distance, heterozygosity 0.35, R-squared &lt; 0.16 -using HapMap's LD files based on CEPH). This resulted in selection of a set of 25,436 SNP LD-free genome wide markers for linkage.
We have performed genome-wide linkage analysis for 21 of the genotyped high-risk lethal prostate cancer pedigrees with the 25,436 selected SNP markers. Genome wide hetLODs showed one significant linkage peak for the recessive model on chromosome 14 (LOD = 4.20). The pedigree with the highest LOD in this region has a +2.69; we are attempting to expand sampling for other pedigrees with linkage evidence in this region.
A single pedigree with 16 prostate cancer cases, at least 4 of whom have already died from prostate cancer and were sampled, provided a LOD score = +3.56 on chromosome arm 11p15. An 11p15 haplotype inherited in common from the founder to 6 generations of descendants is shared in at least 9 of the prostate cancer cases, 3 of whom died from prostate cancer.
The 1-LOD drop defined support interval for the pedigree linked to chromosome 11 occurs at approximately 34-46 cM and contains 13 currently documented genomic features, several of which may be reasonable candidates for lethal prostate cancer including the gene PRMT3 (arginine methyltransferase 3), DAL-1, NELL1, FANCF (Fanconi anemia, complementation group F), and GAS2 (growth arrest-specific 2).
Sequencing of multiple haplotype sharing cases in the pedigree is underway.
Citation Format: Lisa A. Cannon-Albright, Craig C. Teerlink, Neeraj Agarwal. Identification of significant linkage evidence for lethal prostate cancer on chromosome arm 11p15. [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 1341. doi:10.1158/1538-7445.AM2013-1341
Abstract 1345: Evidence for genetic mediation of lung cancer through hay fever.
Authors: D'Amelio Anthony , Nguyen Chi H. , El-Zein Randa , Spitz Margaret R. , Wu Xifeng , Etzel Carol J. 
Published: August 2014

Abstract
Introduction: In the past decade, advances in genetics have led to the discovery of numerous lung cancer susceptibility variants. The majority of these variants have been found to influence lung cancer susceptibility via tobacco exposure or nicotine addiction; however, recently, researchers have observed lung cancer susceptibility variants that mediate through Chronic Obstructive Pulmonary Disease (COPD). Studies involving potential genetic factors related to other lung-related conditions, such as pneumonia and/or hay fever have been limited. The genetic variants related to underlying mechanism of hay fever on the development of lung cancer are interesting to pursue as hay fever has been showed to be protective against lung cancer.
Methods: Cases included 1154 histological-confirmed Caucasian lung cases from MD Anderson Cancer Center in Houston, Texas, and controls included 1137 individuals recruited through the Kelsey-Seybold Clinics in Houston, Texas. These cases and controls were a subset of participants from a lung cancer case-control study conducted that has available Genome-wide association study (GWAS) data (317,498 SNPs). We first conducted an association analysis in PLINK to determine the association of each SNP with both lung cancer and hay fever and find SNPs that showed a joint significance for both hay fever and lung cancer in opposite directions (p-value &lt; 0.05 for both). We then performed mediation analyses with the SNPs that showed significance for both hay fever and lung cancer. Finally, we inferred SNPs in regions that contained a collection of tag SNPs that mediate lung cancer risk through hay fever.
Results: Two hundred and forty six SNPs were found to be statistically significant (p-value &lt; 0.05) for both hay fever (protection) and lung cancer (risk), and 76 of these SNPs maintained their significance level after mediation analysis. SNP rs7159751 on chromosome 14 had the highest mediation effect of 19.83%. A collection of SNPs on the Neuregulin 3 gene (NRG3) that mediate lung cancer risk through hay fever was found on Chromosome 10 which has been shown to activate the JAK-STAT signal transduction pathway and stimulate lung epithelial cell proliferation.
Conclusion: This is the first study to have investigated the mediation effects of hay fever on lung cancer risk. Our data supports the mediation role of certain SNPs in lung cancer through hay fever and points to specific transduction pathway. Future studies are needed to validate these results in external populations.
Citation Format: Anthony D'Amelio, Chi H. Nguyen, Randa El-Zein, Margaret R. Spitz, Xifeng Wu, Carol J. Etzel. Evidence for genetic mediation of lung cancer through hay fever. [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 1345. doi:10.1158/1538-7445.AM2013-1345