bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2614: Distinguished features of ERG oncoprotein expression among matched cohorts of African-American and Caucasian-American prostate cancer patients
Authors: Dobi Albert L. , Rosen Philip , Pfister David , Young Denise , Chen Yongmei , Petrovics Gyorgy , McLeod David , Srivastava Shiv , Sesterhenn Isabell 
Published: August 2012

Abstract
Introduction and Objective: The ETS-related gene (ERG) proto-oncogene is frequently overexpressed in prostate cancer (CaP) as a result of a genomic rearrangement that places ERG under the control of the androgen-dependent TMPRSS2 promoter. The initial report of quantitative ERG mRNA expression in micro-dissected prostate tumor cells showed significantly higher ERG expression in CaP of Caucasian-Americans (CA) patients vs. African-American (AA) patients (Petrovics et al, Oncogene, 2005). Recent studies (Magi-Galluzzi et al, Prostate, 2011; Elliott et al, USCAP Mtg., 2011) have also shown higher frequency of ERG rearrangement or ERG oncoprotein expression in CaP of CA patients. We evaluate the frequency and pattern of the ERG oncoprotein expression in prostate tumors of matched CA and AA CaP patients to better understand the biological basis for differences in prostate cancer between the two populations. Methods: Ninety one AA and 91 CA CaP patients were matched for age, Gleason score and pathologic stage. All underwent radical prostatectomy between 1993 and 2010. Whole mount prostate specimens were used for the immunohistochemical detection of the ERG oncoprotein by a highly specific ERG monoclonal antibody (clone 9FY). Individual foci of tumors were reported as either positive or negative. ERG staining data was linked to clinico-pathologic data. Biochemical recurrence was defined as two serum PSA measurements of 0.2 ng/mL or higher at least 8 weeks from surgery. Results: A higher percentage of CA (61.8%) than AA (28.2%) CaP patients had ERG positive index tumors and had at least one focus of tumor positive for ERG. A higher percentage of overall tumor foci were also positive for ERG in CA than AA CaP patients. There was high concordance of ERG positive prostatic intra-epitheilal neoplasia (PIN) and ERG positive CaP in both AA and CA patients. Conclusions: ERG expression is more prevalent among CA than AA CaP patients in matched cohorts. Differences in the pattern of ERG expression in CaP and differing trends in biochemical recurrence between CA and AA patients with ERG (+) index tumors suggest a dominant clonal selection of ERG-positive tumors in CA patients. These differences in ERG expression have the potential to delineate biological distinctions of CaP in the two patient populations. Acknowledgement: This study was supported in part by USU-CPDR and NIH grant CA162383 to SS.
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 2614. doi:1538-7445.AM2012-2614
Abstract 2617: Cytokine and cytokine receptors of adaptive immune response are differentially associated with breast cancer risk in women of African ancestry and European ancestry
Authors: Quan Lei , Yao Song , Gong Zhihong , Bandera Elisa V. , Hwang Helena , Roberts Michelle , Zirpoli Gary , Ciupak Gregory , Davis Warren , Sucheston Lara , Pawlish Karen , Bovbjerg Dana , Jandorf Lina , Ambrosone Christine B. , Hong Chi-Chen 
Published: August 2012

Abstract
Disparities in breast cancer biology are evident between women of African ancestry (AA) and women of European ancestry (EA), and may be due, in part, to differences in inflammatory pathway genes. Studies on the relationships between cytokines and breast cancer risk have focused on a small number of genes and have not included AA women. In a large case-control study of 1008 AA (n=547 cases) and 763 EA (n=381 cases) women, we systematically tested the association between risk of breast cancer and single-nucleotide polymorphisms (SNPs) in 22 cytokine and cytokine receptor genes involved in adaptive immune response pathways. Logistic regression was used to estimate odds ratios and 95% confidence intervals in a genotypic (co-dominant) model adjusting for major breast cancer risk factors including age, education, body mass index (BMI), family history of breast cancer and proportion of European ancestry. All analyses were stratified on race. SNPs rs17810546 in IL12A (interleukin 12A), rs1041981 in LTA (lymphotoxin alpha), and rs3135932 in IL10RA, were associated with breast cancer risk in AA but not EA women. When stratifying by menopause and ER status, SNPs rs2070874 in IL4, rs1041981 in LTA and rs2430561 in IFNG (interferon gamma) were associated with breast cancer risk in pre-menopausal AA women, and SNPs rs2243248 in IL4 and rs746868 in LTA were associated with ER-negative breast cancer in EA women. Common variants in inflammatory pathway genes may help to define populations at high risk of breast cancer. Notable differences in distributions of SNPs and associations by ancestry may be related to the differential epidemiology of breast cancer in AA and EA women.
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 2617. doi:1538-7445.AM2012-2617
Abstract 2622: SNP markers in the FGF9 and MAP3K1 region associate with testicular germ cell tumor susceptibility
Authors: Koster Roelof , Kanetsky Peter A. , Mitra Nandita , Vardhanabhuti Saran , Ciosek Stephanie L. , Letrero Richard , D'Andrea Kurt , Doody David R. , Chen Chu , Vaughn David J. , Schwartz Stephen M. , Nathanson Katherine L. 
Published: August 2012

Abstract
Testicular germ cell tumors (TGCT) are the most common cancers in young men, and several lines of evidence point to their substantial genetic component. To date, genome-wide association (GWA) studies have uncovered six TGCT susceptibility loci. Together these loci account for 11-16% of TGCT disease risk to first degree relatives, arguing that additional genetic variation contributing to TGCT susceptibility must exist. Recently we and others indentified variation at DMRT1 associated with TGCT risk. DMRT1 is highly conserved across many species and plays a crucial role in male gonadal development and sex determination. Deletions in DMRT1 lead to male to female (XY) sex reversal. Therefore, we undertook a targeted pathway-based analysis of genes influencing XY sex reversal to identify associations with TGCT risk. Through review of the literature, we identified 27 additional genes in which mutations or deletions are associated with XY sex reversal. Using our existing GWA data in 349 cases and 919 controls, ∼570 risk markers in the 28 candidate loci were evaluated for replication based on a significance threshold of p &lt; 2 x 10−5 for at least two SNP markers. Two markers that mapped near to MAP3K1 and FGF9 meet these criteria. We genotyped the most statistically significant SNP markers in the MAP3K1 (rs252906; p = 1.89 x 10Δ5) and FGF9 (rs628137; p = 1.66 x 10Δ5) region in two independent replication sample sets, consisting of 439 cases of TGCT and 960 controls and of 768 cases and 674 controls respectively. In combined analysis, TGCT cases had elevated odds of carriage of the rs252906 major T allele [per-allele odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16, 1.377; P = 5.87 × 10−5] and the rs628137 major G allele (per allele OR = 1.20, 95% CI 1.08, 1.34, P = 5.28 x 10−4 compared with controls. Similarly to KITLG, the susceptibility locus most strongly associated with TGCT risk, FGF9 is associated with proliferation, migration and survival of primordial germ cells, the progenitor cells for human TGCT. MAP3K1 and FGF9 play a crucial role in normal testes development. These finding strengthen the supposition that variation in genes influencing sex determination, and male germ cell development and differentiation play an important role in inherited TGCT susceptibility.
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 2622. doi:1538-7445.AM2012-2622
Abstract 2623: The role of polymorphisms in DNA repair genes and HPV 16 integration status in cervical dysplasia
Authors: Amirian E. Susan , Marquez-Do Deborah , Adler-Storthz Karen , Follen Michele , Scheurer Michael E. 
Published: August 2012

Abstract
BACKGROUND: Cervical cancer is the second leading cause of death in women worldwide, and yet, little is understood about why some HPV-infected women develop cancerous lesions while others are able to clear the infection with no sequelae. Previous evidence has indicated that HPV integration status may be associated with cervical cancer development and progression. However, host genetic variation within genes that may play important roles in the viral integration process has been understudied. The purpose of this study was to examine the association between both HPV 16 viral integration status and single nucleotide polymorphisms (SNPs) in non-homologous end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia, comparing women with no dysplasia to those with low-grade or high-grade squamous intraepithelial lesions. METHODS: A total of 765 women were selected from two large trials designed to evaluate optical technologies for cervical cancer, being conducted at MD Anderson Cancer Center, Lyndon B Johnson General Hospital, and the British Columbia Cancer Agency. Genotyping was conducted using the Illumina Golden Gate platform; individuals with call rates &lt;85% were excluded from the analyses. HPV integration status was determined using an assay described in the literature. Chi-square and Fisher's exact tests were conducted to determine which SNPs were significantly associated with normal cytology, low-grade, or high-grade lesions. Among participants with cervical dysplasia, chi-square tests and polytomous logistic regression models were used to evaluate the effect of each polymorphism on viral integration status. We used an additive genetic model for all tests. P-values were adjusted using the false discovery rate method and FDR-adjusted q values are reported. RESULTS: Women with high-grade lesions were significantly younger than women with low-grade or no lesions. Tag-SNPs in 13 DNA repair genes, including RAD50, WRN, and XRCC5, were significantly associated with cervical dysplasia. HPV16 integration status was differential across cervical cytology, but overall, most participants had a mix of both episomal and integrated HPV 16. Four tag-SNPs in the XRCC4 gene were found to be significantly associated with HPV 16 integration status. CONCLUSION: Our findings indicate that host genetic variation in NHEJ DNA repair pathway genes, specifically XRCC4, are significantly associated with HPV integration, and that these genes may play an important role in determining cervical cancer development and progression. This is the first time that host genetic variation has been linked to the viral integration event.
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 2623. doi:1538-7445.AM2012-2623
Abstract 2624: Evaluation of the association of the ABO blood group SNP rs505922 with breast cancer phenotypes
Authors: Rummel Seth K. , Ellsworth Rachel E. , Shriver Craig D. 
Published: August 2012

Abstract
Purpose: To date, evaluation of the association of the ABO blood group and breast cancer has yielded mixed results. SNP rs505922, located within the first intron of the ABO gene, has been associated with the adenocarcinoma subtype of pancreatic cancer. To determine whether the ABO blood group is associated with risk of breast cancer, rs505922 was genotyped in 629 Caucasian women with invasive breast cancer, representing a variety of clinical and pathological tumor types. Methods: Genomic DNA was isolated from blood clots. TaqMan SNP assay C_2253769_10 was used to determine the genotypes for rs505922. Statistical analysis was performed using chi-square analysis using a P-value &lt;0.05 to define significance. Results: Genotypes were generated for 100% of the 629 patients in this study. Allele and genotype frequencies did not vary significantly for age at diagnosis, tumor stage, size or grade, hormone, HER2 or lymph node status, intrinsic subtype, tumor type or patient outcome. Conclusions: Allele frequencies for rs505922 did not differ between women with breast cancer and published HapMap frequencies. Further stratification into different tumor phenotypes also failed to reveal an association between rs505922 and any tumor characteristics. Together, these data suggest that the minor allele of rs505922 and the resulting non-O blood types, are not associated with increased risk or less favorable tumor characteristics or prognosis in breast cancer.
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 2624. doi:1538-7445.AM2012-2624
Abstract 2627: Polymorphisms of retinol transporter genes and risk of head and neck cancer
Authors: Chang Jeffrey S. , Hsiao Jenn-Ren , Wong Tung-Yiu , Tsai Sen-Tien , Ou Chun-Yen , Lo Hung-I , Huang Cheng-Chih , Lee Wei-Ting , Chen Ken-Chung , Huang Jehn-Shyun , Wang Yi-Hui , Weng Ya-Ling , Yang Han-Chien 
Published: August 2012

Abstract
Background: Retinoic acid is important for cell growth, differentiation, and apoptosis, which when dysregulated may predispose the development of cancer. Retinoic acid metabolism can be influenced by ethanol, cigarette smoking, and areca nut, the three major risk factors of head and neck cancer (HNC). A previous genome-wide association study reported an association between serum retinol level and two single nucleotide polymorphisms (SNPs) in two retinol transporter genes (TTR rs1667255 and RBP4 rs10882272) (1). The current study assesses the association between these two SNPs and HNC risk. Methods: 133 incident cases of HNC and 128 sex- and age- matched controls were recruited from the department of otolaryngology and department of stomatology. Data on the use of alcohol, cigarette, and areca nut were ascertained through in-person interview. Genotyping of TTR rs1667255 and RBP4 rs10882272 was performed using the Taqman-based real-time PCR method. Unconditional logistic regression was performed to estimate HNC risk associated with the two SNPs. Results: No association between HNC risk and TTR rs1667255 or RBP4 rs10882272 was observed. However, the two SNPs appeared to modify the relationship between alcohol consumption and HNC risk. There was an increased risk of HNC associated with daily alcohol drinking only among subjects with the “high serum retinol genotypes” (CC for TTR rs1667255: odds ratio (OR) = 4.6, 95 confidence interval (CI): 1.3-16.3; TT for RBP4 rs10882272: OR = 2.3, 95% CI: 1.2-4.4). While daily alcohol drinking was not associated with an increased risk of HNC among subjects with the “low serum retinol genotypes” (AA or AC for TTR rs1667255: OR = 1.4, 95% CI: 0.7-2.9; TC or CC for RBP4: OR = 0.7, 95% CI: 0.1-3.6). Conclusion: The association between alcohol consumption and HNC risk is modified by the polymorphisms of retinol transporter genes. Reference: 1. Mondul AM, Yu K, Wheeler W, et al. Genome-wide association study of circulating retinol levels. Human molecular genetics 2011;20:4724-31.
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 2627. doi:1538-7445.AM2012-2627
Abstract 2716: Development of tanapox virus for oncolytic therapy
Authors: Seibert Krystal N. , Essani Karim , Bejcek Bruce E. 
Published: August 2012

Abstract
Vaccinia virus has been included in the many viruses that have been used to target cancer cells. However, vaccinia virus has some drawbacks in that it infects both tumor and non-tumor cells (Guo, Z. S. etal. 2005 Cancer Research 65: 9991-9998), and hosts often have a pre-existing immunity to it (Hu, Y. etal. 2001 J. Virol. 75, 10300-10308). Due to these drawbacks with vaccinia virus we are developing a poxvirus family member, tanapox virus (TPV), for use as an oncolytic therapy. TPV does not cross-react with vaccinia virus antibodies, replicates in human cells, and results in a relatively mild infection under normal conditions making it safer to work with (Paulose, M. etal. 1998 Microbial Pathogenesis 25, 33-41). Tumor suppressor protein p53 is mutated in over half of all cancers making it a promising target for virotherapy. In this study we characterized the 142R protein of TPV, demonstrating its potential as a conditionally replicating oncolytic virus. By analyzing the sequence of 142R it was determined that the protein has a serine-threonine kinase domain that is homologous to the vaccinia virus B1R gene that has been shown to phosphorylate p53. Viral tropism towards cancer can be enhanced by engineering the virus to be conditionally replicating (Vähä-Koskela, M. J. V. etal. 2007 Cancer Letters 254, 178-216), such as the adenovirus ONYX-015 in which the E1B gene has been deleted, restricting its replication to cells not containing a wild-type p53. When comparing the sequence of 142R to B1R we showed that 142R had 50% identity to B1R. 142R also has the same nucleotide binding, phosphotransfer and proton transfer, ATP binding and catalytic domain indicator regions as B1R. We then created a plasmid with 142R that was transfected into COS-7 cells, harvested and the protein eluted from a cobalt column. This protein was then used in a protein kinase assay against p53. This indicates that the 142R protein of TPV is capable of interacting with p53 so is a good candidate for creating a conditionally replicating virus.
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 2716. doi:1538-7445.AM2012-2716
Abstract 2719: MM-141, a novel bispecific antibody co-targeting IGF-1R and ErbB3, blocks ligand-induced signaling and demonstrates antitumor activity
Authors: Baum Jason , Johnson Bryan , Adams Sharlene , Tang Jian , Kohli Neeraj , Rennard Rachel , Sundararajan Pragalath , Xu Lihui , Jiao Yang , Schoeberl Birgit , Nielsen Ulrik , Fitzgerald Jonathan , Lugovskoy Alexey 
Published: August 2012

Abstract
Monoclonal antibodies have significantly advanced our ability to treat cancer, but most patients do not show durable responses to therapy. This, in part, can be explained by the tumor cells responding to two or more growth factors in a redundant fashion. We show that cancer cell lines frequently rely on Insulin-like growth factor 1 (IGF-1) and Heregulin (HRG) signaling to support their survival and proliferation. Using a Network Biology approach, we have designed, constructed and optimized a novel bispecific antibody, MM-141, for co-targeting of ErbB3 and IGF-1R. MM-141 blocks IGF-1, IGF-2, and HRG binding to IGF1R and ErbB3, and causes downregulation of these receptors. MM-141 inhibits phosphorylation of IGF1R and ErbB3 as well as downstream activation of the PI3K/Akt pathway. In our in vitro and in vivo testing, MM-141 displays potency in the presence of single or multiple ligands, over a broad range of receptor profiles. Inhibition of growth by MM-141 has been observed in vitro as well as in vivo in multiple xenograft models including human pancreatic cancer (BxPC-3) and human prostate cancer (DU145). MM-141 does not bind the insulin receptor, thus reducing the risk of metabolic side effects. Our in vivo and in vitro studies reveal that MM-141 has favorable pharmaceutical properties and pharmacokinetic profiles. We are advancing MM-141 into preclinical development. Taken together, these results suggest that MM-141 has the potential to be an effective therapeutic for treatment of patients with solid tumors.
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 2719. doi:1538-7445.AM2012-2719
Abstract 2801: Dual Targeting Glioblastoma Multiforme (GBM) with a Phosphatidylinositol 3-kinase inhibitor (ZSTK474) and a Proteasome Inhibitor (Velcade)
Authors: Yin Dong , Gaut Daria , Ho Quoc H. , Koeffler H. Phillip 
Published: August 2012

Abstract
Proteasome inhibitor has been proven to be an effective anticancer compound in many tumor models, including Glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) activated the PI3K/Akt pathway although causing GBM cells death. Therefore, we sought to investigate if the PI3K inhibitor, ZSTK474, would enhance the effectiveness of PS-341 in anticancer therapy. Three GBM cells lines (U87, U251, U138) were exposed to Velcade (10-7 M, 24 hr). We found that phosphorylation of Akt, 4E binding protein-1 (4EBP1), and mammalian target of rapamycin (mTOR) was induced by Valcade in these GBM cells compared to the controls. To study the role of the PI3K/Akt signal pathway in the Velcade induced growth arrest in GBM cells, this pathway was blocked using the PI3K inhibitor ZSTK474. These three cell lines were treated with serial dilutions of either Velcade or ZSTK474 or both drugs together, and MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide] assay results showed that combination of ZSTK474 and Velcade synergistically inhibited proliferation of GBM cell lines. In the presence of ZSTK474, the phosphorylation of Akt, 4EBP1, and mTOR was markedly decreased in all cell lines. Cells apoptosis was increased when exposed to Velcade and ZSTK474 in combination as shown by Annexin V analysis. To confirm the decrease of p-4EBP1 in the presence of both drugs, the unphosphorylated binding protein 4EBP1 was also detected. In all cell lines in the presence of Velcade and ZSTK474, 4EBP1 becoming unphosphorylated. Cyclin D1, another protein promoting proliferation in the PI3K/Akt pathway, was up-regulated in the presence of Velcade alone, but down-regulated in the presence of both Valcade and ZSTK474 together. In summary, the anticancer ability of Valcade is increased by combination with PI3K pathway inhibitor ZSTK474 in glioblastoma multiforme.
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 2801. doi:1538-7445.AM2012-2801