bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 821: Human mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasis
Authors: Holland James F. , Melana Stella , Jaffer Shabnam , Etkind Polly , Nartey Teiko , Lee Tina , Pogo Beatriz G.T. 
Published: August 2015

Abstract
Human Mammary Tumor Virus (HMTV), a betaretrovirus 90-95% homologous to Mouse Mammary Tumor Virus (MMTV), present in 40% of American women's breast cancers, but not in the normal tissue from the same breast indicates an infection (Cancer Res 1995, 55:5173-79). Absence of murine intracisternal particles and murine cyclo-oxygenase 2 by PCR and nanoString excludes contemporaneous mouse DNA, and thus MMTV contamination (Proc AACR 2014 #1595). We have detected the entire 9.9 kb proviral sequence. Proviral DNA is visible in nuclei by FISH, and budding virus was observed by EM. HMTV in cells is present in the milk of 8% of unselected American women, but in 21% if they had had a prior biopsy based upon clinical or radiologic suspicion of a mass. (Infectious Agents and Cancer 2014, 9:20).
HMTV has been found in cells of 30 of 32 (94%) metastatic breast cancer effusions (MSSM cells). HMTV protein and virion RNA were detected in MSSM cells but not in normal human mammary epithelium. (J Virol Methods 2010,163:157-61). HMTV isolated from MSSM cells is infectious for B and T lymphocytes, MCF10A andF and human mammary epithelial cells (HMEC). Infection led to proviral insertion sites with different flanking sequences. Epithelial-mesenchymal transition was observed with upregulation of vimentin and downregulation of E-cadherin. Restriction factors including the cytidine deaminase APOBEC G and F, TRIM 5, 21 and 25 and Tetherin were also increased after in vitro HMTV infection.
Epidemiologically, breast cancer is less frequent in 5 countries of Central and East and Asia (28-43/100,000/y. World Cancer Report 2014) where HMTV positivity in breast cancers ranges from 0 to 20%, compared to 7 countries of Western Europe and its former colonies in North and South America and Australia (47-92/100,000/y op.cit.) where 30 to 60% are positive. This correlates with indigenous mouse species, Mus musclus and M.castaneus in the East, and M. domesticus with much more HMTV in its genome in the West.
HMTV positive lymphomas have been reported in patients with HMTV positive breast cancers (Clin Cancer Res 2004 10:56565-64). The parallel with MMTV behavior in the mouse with respect to breast cancer and lymphomas is striking. These composite data support a significant role of HMTV in human breast cancer and its metastatic process.
Citation Format: James F. Holland, Stella Melana, Shabnam Jaffer, Polly Etkind, Teiko Nartey, Tina Lee, Beatriz G.T. Pogo. Human mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 821. doi:10.1158/1538-7445.AM2015-821
Abstract 822: Genetically engineered mouse models of catastrophic pancreatic ductal adenocarcinoma
Authors: Yamaguchi Takashi , Ikehara Sanae K. , Nakanishi Hayao , Ikehara Yuzuru 
Published: August 2015

Abstract
Carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has been well studied using genetically engineered mouse (GEM) models with abnormalities in activation of both RAS and E2 factor (E2F)-which is associated with the Rb-E2F pathway, and dysfunction of p53-which is associated with the transformed 3T3 cell double minute 2 (MDM2)-p53 pathway. Catastrophic progression of the malignancy is one of unique manifestation, which has not been recapitulated in the GEMs to study underlined mechanisms, while we have recently reported a new GEM developing PDAC to die in 3 weeks after birth due to the catastrophic progression [Yamaguchi T. et al, J Pathol. 2014; 234(2):228-138]. The GEM had the specific expression of SV40 tsA58 large T antigen (tsTAg) to inhibit p53 and Rb family molecules (Rb1, Rbl1 and Rbl2) on pancreas with the expression of oncogenic Kras (KrasG12D) by Pdx1 promoter-mediated Cre-loxP recombination.
In this study, we sought to determine if the induced tsTAg on pancreatic epithelial cells with constitutive KrasG12D expression are enough to develop PDAC and catastrophic manifestation, by the generation of a new GEM based on Cre-loxP recombination and Tet-On system. In the GEM, KrasG12D constitutively expresses on pancreatic epithelial cells after the Cre-loxP recombination under the control Pdx1 promoter, while tsTAg expression can be regulated by Tet-On system after the recombination by Pdx1 promoter. Any of the mice did not developed PDAC within 6 month, but all of the mice developed PDAC by Dox administration in within 1 week and died by the progression of PDAC within 3 weeks after the start.The rapid progression and development of PDAC appeared to be associated with the stronger tsTAg expression depending on reverse tetracycline trans-activator.
These results demonstrated that KrasG12D driven PDAC carcinogenesis was promoted by the presence of tsTAg expression, resulting in production of PDAC cells with aggressive growth. In conclusion, our established new mouse model can contribute to increase knowledge about catastrophic PDAC.
Citation Format: Takashi Yamaguchi, Sanae K. Ikehara, Hayao Nakanishi, Yuzuru Ikehara. Genetically engineered mouse models of catastrophic pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 822. doi:10.1158/1538-7445.AM2015-822
Abstract 823: Gene expression profiling for oncogenic Kras mutation in mice and human colorectal cancer
Authors: Niitsu Hiroaki , Hinoi Takao , Kawaguchi Yasuo , Sentani Kazuhiro , Oue Naohide , Sotomaru Yusuke , Adachi Tomohiro , Saito Yasufumi , Miguchi Masashi , Kochi Masatoshi , Shimomura Manabu , Yasui Wataru , Ohdan Hideki 
Published: August 2015

Abstract
Purpose: Oncogenic KRAS mutations are found in 40-50% of human colorectal cancers. However, specific therapeutics has not been yet available. We aimed to search new therapeutic molecular targets or biomarkers in KRAS mutated colorectal cancers.
Experimental design: We generated Apcflox/flox; CDX2P9.5-G22Cre and LSL-KrasG12D; Apcflox/flox; CDX2P9.5-G22Cre mice, that had been considered as sporadic colon cancer mouse model with Kras wild and mutant, respectively. We observed the carcinogenesis at the age of 3-4 weeks by necropsy, and harvested the tumors for gene expression profiling. We compared the gene expression by Microarray (GeneChip, Affymetrix) between each 3 tumors from these mice strains. Genes with &gt;5 fold changes between the two groups were selected as candidate genes, and subsequently narrow these down by bibliographic search for further analyses in human colorectal cancers.
Result: In macroscopic findings, extensive polyps were generated in cecum and proximal colon, but not in other site of gastrointestinal tract. Tumors occurred in the both strains were considered as well differentiated adenocarcinomas in hematoxylin-eosin staining. It was confirmed that tumors generated in Apcflox/flox; CDX2P9.5-G22Cre mice had Cre-targeted Apc 580D alleles and wild-type Kras, and that tumors generated in LSL-KrasG12D; Apcflox/flox; CDX2P9.5-G22Cre mice had both Cre-targeted Apc 580D alleles and activated oncogenic KrasG12D. In the subsequent gene expression profiling, we identified 31 genes with &gt;5 fold change in Microarray analyses. Of these, we focused on some genes that showed lower expression in Kras mutant tumor than in Kras wild type tumor. We confirmed the lower expressions of these genes in murine tumors by quantitative RT-PCR, and the lower expression in early-staged human colorectal cancers with oncogenic KRAS mutant by immunohistochemistry staining. To analyze the functions, the retroviral vectors that lead overexpression of these genes were constructed and infected to SW480 and RKO CRC cell lines. Proliferation and migration is being analyzed using these cell lines.
Conclusion: We identified novel genes associated with oncogenic KRAS mutation, using the analyses of gene expression in colon cancer mouse model.
Citation Format: Hiroaki Niitsu, Takao Hinoi, Yasuo Kawaguchi, Kazuhiro Sentani, Naohide Oue, Yusuke Sotomaru, Tomohiro Adachi, Yasufumi Saito, Masashi Miguchi, Masatoshi Kochi, Manabu Shimomura, Wataru Yasui, Hideki Ohdan. Gene expression profiling for oncogenic Kras mutation in mice and human colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 823. doi:10.1158/1538-7445.AM2015-823
Abstract 828: Methylation status of HPV16 E2-binding sites identifies subtypes of HPV-associated oropharyngeal squamous cell carcinomas
Authors: Speel Ernst-Jan M. , Reuschenbach Miriam , Huebbers Christian U. , Prigge Elena-Sophie , Bermejo Justo L. , Kalteis Simon , Preuss Simon , Kolligs Jutta , Olthof Nadine C. , Kremer Bernd , Wagner Steffen , Klussmann Jens P. , Vinokurova Svetlana , von Knebel Doeberitz Magnus 
Published: August 2015

Abstract
Background: The viral E2 protein is a transcriptional repressor of the HPV oncogenes E6/E7 and loss of E2 function is considered a key step in carcinogenesis. Integration of HPV into the host genome may disrupt the E2 gene. Furthermore, methylation of CpG dinucleotides in E2 binding sites (E2BSs) in the HPV upstream regulatory region (URR) may interfere with transcriptional repression of E6 and E7 by the E2 protein. We hypothesized that CpG methylation of the E2BS is found in a proportion of HPV16-associated oropharyngeal squamous cell cancers (OPSCC) in association with E2 gene integrity and viral integration.
Methods: Methylation of 10 CpGs within the URR, encompassing E2BSs 1, 2, 3 and 4, was quantitatively analyzed by bisulfite pyrosequencing in 57 HPV16-associated OPSCC. E2 status was analyzed by gene amplification and quantitative real-time RT-PCR. Viral integration was determined by integration-specific PCR methods.
Results: Three subgroups with differential E2BSs3 and 4 methylation were identified: a) complete methylation (&gt;80%) associated with presence of integrated HPV genomes with intact E2 gene, b) intermediate methylation levels (20-80%) with predominantly episomal HPV genomes with intact E2, and c) no methylation (&lt;20%) with integrated HPV with disrupted E2. Patients with complete and without methylation had poor 5-year overall survival compared to patients with intermediate methylation (stage-adjusted hazard ratio 3.8 (95%CI 1.3-11.2) and 3.1 (95%CI 1.14-8.28); p = 0.03).
Conclusions: E2BSs3 and 4 methylation in oropharyngeal cancers with episomal HPV and integrated HPV with intact E2 gene might explain deregulated viral oncogene expression in the presence of E2. The methylation level appears to be of prognostic significance for patients with HPV-associated OPSCC.
Citation Format: Ernst-Jan M. Speel, Miriam Reuschenbach, Christian U. Huebbers, Elena-Sophie Prigge, Justo L. Bermejo, Simon Kalteis, Simon Preuss, Jutta Kolligs, Nadine C. Olthof, Bernd Kremer, Steffen Wagner, Jens P. Klussmann, Svetlana Vinokurova, Magnus von Knebel Doeberitz. Methylation status of HPV16 E2-binding sites identifies subtypes of HPV-associated oropharyngeal squamous cell carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 828. doi:10.1158/1538-7445.AM2015-828
Abstract 833: Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers
Authors: Weng Daniel Y. , Chen Jinguo , Taslim Cenny , Hsu Ping-Ching , Marian Catalin , David Sean P. , Loffredo Christopher A. , Shields Peter G. 
Published: August 2015

Abstract
The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacco products. We assessed the effects of smoking on the gene expression in vitro and in vivo using human cell cultures and blood from a cross-sectional study. We profiled global transcriptional changes in cultured smokers’ peripheral blood mononuclear cells (PBMCs) treated with cigarette smoke condensate (CSC) in vitro and from well-characterized smokers’ blood (n = 36). ANOVA and linear regression with adjustment for covariates were used for statistical analysis. CSC in vitro altered the expression of 1178 genes (177 genes with &gt; 1.5 fold-change) at P &lt; 0.05. Phase I and II metabolizing enzyme genes were up-regulated, cytokines and chemokines were down-regulated. Nine putative oncogenes and 5 tumor suppressor genes were dysregulated. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29 with &gt; 1.5 fold-change) at P &lt; 0.05 (309 remaining significant after adjustment for age, race and gender). Seventy eight genes had a significant linear correlation (P &lt; 0.01) with cigarettes per day and 28 genes were linearly correlated with cumulative pack-year smoking. Forty-one genes were persistently altered both in vitro and in vivo, 22 having the same expression pattern reported for non-small cell lung cancer. Our data provides evidence that persistent alterations of gene expression in vitro and in vivo may relate to carcinogenic effects of cigarette smoke, and the identified genes may serve as potential biomarkers for cancer. The use of an in vitro model to corroborate results from human studies provides direct evidence for a cause and effect.
Citation Format: Daniel Y. Weng, Jinguo Chen, Cenny Taslim, Ping-Ching Hsu, Catalin Marian, Sean P. David, Christopher A. Loffredo, Peter G. Shields. Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 833. doi:10.1158/1538-7445.AM2015-833
Abstract 839: Effects of occupational exposure to carbon black on peripheral white blood cell counts
Authors: Dai Yufei , Zhang Rong , Niu Yong , Duan Huawei , Meng Tao , Ye Meng , Shen Meili , Bin Ping , Yu Shanfa , Vermeulen Roel , Rothman Nathaniel , Lan Qing , Zheng Yuxin 
Published: August 2015

Abstract
Carbon black (CB) is a material produced by the combustion of hydrocarbon gases or liquids and widely used in various industrial settings. The International Agency for Research on Cancer has classified CB as possibly carcinogenic to humans. Previous studies suggest that CB might induce lung inflammation and injury and it is well known that inflammation can play an important role in tumor development. However, the relationship between CB exposure and peripheral white blood cell counts is still not clear. To address this issue, we conducted a cross-sectional molecular epidemiology study of 106 CB-exposed male workers responsible for packing CB in a CB manufacturing facility that produced very high purity CB and 112 unexposed male control workers from the same geographic region who were frequency-matched to the exposed workers by age. The average number of years worked in the factory for the exposed workers was 12.5 years. Peripheral blood samples were collected and a complete blood cell count (CBC) and lymphocyte subset analysis were conducted. There was a borderline significant increase in eosinophil count, and a significant decrease in total lymphocyte and NK cell counts, among the exposed vs. control workers. Among non-smokers (35 exposed and 29 controls), CB exposure was associated with a borderline significant increase in total white blood cell and neutrophil counts, a significant increase in eosinophil counts, and a significant decrease in total lymphocyte, CD3+ T cell, CD8+ T cell and NK cell counts. There were no significant differences between exposed and control workers for any white blood cell measure among smokers. Also, there was some evidence of an interaction between carbon black exposure and smoking status for neutrophil, total lymphocyte, CD3+ T cell, and CD8+ T cell counts. Our results suggest that CB exposure may be associated with altered levels of cells that play an important role in the inflammatory process among non-smokers. Also, there was evidence for an interaction between CB exposure and tobacco use. These findings may provide new insights into particulate-associated disease.
Citation Format: Yufei Dai, Rong Zhang, Yong Niu, Huawei Duan, Tao Meng, Meng Ye, Meili Shen, Ping Bin, Shanfa Yu, Roel Vermeulen, Nathaniel Rothman, Qing Lan, Yuxin Zheng. Effects of occupational exposure to carbon black on peripheral white blood cell counts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 839. doi:10.1158/1538-7445.AM2015-839
Abstract 840: Occupational exposure to trichloroethylene and LINE-1 methylation
Authors: Hu Wei , Zhang Luoping , Kim Christopher , Tang Xiaojiang , Kim4 Sungkyoon , Bassig Bryan , Seow Wei-Jie , Shen Min , Qiu Chuangyi , Ge Yechen , Reiss Boris , Purdue Mark , Moore Lee , Li Laiyu , Yue Fei , Huang Hanlin , Smith Martyn T. , Vermeulen Roel , Rothman Nathaniel , Lan Qing 
Published: August 2015

Abstract
Trichloroethylene (TCE) is a volatile chlorinated organic compound that is commonly used in industrial settings as a degreaser. Epidemiologic studies suggest that TCE exposure is associated with an increased risk of kidney cancer and may also be associated with non-Hodgkin lymphoma. However, the mechanisms for these associations are still not clear. To evaluate the relationship between occupational exposure to trichloroethylene (TCE) and LINE-1 methylation, a measure of global methylation, we conducted a cross-sectional molecular epidemiology study of 79 workers exposed to TCE and 81 comparable unexposed controls in Guangdong, China. Personal air exposure measurements and urine samples were collected prior to phlebotomy. The urine TCE metabolite, trichloroacetic acid (TCA), was measured by liquid chromatography electrospray ionization tandem mass spectrometry in urine samples and LINE-1 methylation was assessed by pyrosequencing DNA isolated from peripheral blood. LINE-1 methylation levels [median (range) in percent] were 78.40 (75.80-81.20) in controls, 77.80 (76.10-81.00) in lower exposed, and 77.50 (74.20-80.20) in higher exposed workers based on median urine TCA level (p trend = 0.012). These results suggest that TCE may be associated with a decrease in global methylation measured by the LINE-1 assay. Gene-specific methylation is currently being conducted to follow up these findings.
Citation Format: Wei Hu, Luoping Zhang, Christopher Kim, Xiaojiang Tang, Sungkyoon Kim4, Bryan Bassig, Wei-Jie Seow, Min Shen, Chuangyi Qiu, Yechen Ge, Boris Reiss, Mark Purdue, Lee Moore, Laiyu Li, Fei Yue, Hanlin Huang, Martyn T. Smith, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Occupational exposure to trichloroethylene and LINE-1 methylation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 840. doi:10.1158/1538-7445.AM2015-840
Abstract 841: SNP-FEMS: a method to identify DNA binding proteins interacting with enhancer elements
Authors: Mendoza-Fandino Gustavo A. , Woods Nicholas , Baskin Rebekah , Gjyshi Anxhela , Monteiro Alvaro N. 
Published: August 2015

Abstract
An important goal of human genetics is to understand the etiology of genetic traits. In the past few years, genome-wide association studies (GWAS) have identified thousands of chromosomal loci associated with hundreds of traits. GWAS provide a list of variants (single nucleotide polymorphisms, SNP) that are statistically associated with a phenotype, but do not offer any direct evidence about the biological mechanism. Most GWAS cancer susceptibility loci are located in non-coding regions suggesting that they function by modifying tracsriptional regulatory elements, such as enhancers and promoters of target genes. Thus, methods to help identify transcription factors that interact with regulatory regions containing risk associated variants can reveal biological mechanisms. We developed a method, SNP-FEMS (FPLC, EMSA, Mass Spec) that combines liquid chromatography (FPLC), electrophoretic mobility shift assays (EMSAs), and mass spectrometry to identify transcription factors interacting with putative regulatory regions at the 8q24 ovarian cancer risk locus. Human embryonic kidney 293FT nuclear extract was subjected to Sepharose 6 10/300 GL size fractionation and all the fractions were screened for allele-specific binding proteins by EMSA using a probe containing a genome-wide significant SNP. Fractions with positive signal were combined, concentrated and further fractionated with an ion exchange column MonoQ 5/10 GL to further reduce the complexity of the fractions. Fractions were screened by EMSA with the same probe, and the positive fractions were combined, concentrated, subjected to PAGE, in-gel trypsin digestion, and analyzed by Mass Spectrometry to identify proteins in the fractions. Bioinformatics analysis predicted different transcription factors binding to the putative regulatory region and the only transcription factor that was also present in our experimental dataset was the Cyclin AMP-dependent transcription factor ATF-1. This data suggests that ATF1 is implicated in ovarian cancer susceptibility and demonstrate the utility of the SNP-FEMS method to identify regulatory factors involved in ovarian cancer risk. This technique is applicable to any predisposition loci mediated by changes in regulatory elements.
Citation Format: Gustavo A. Mendoza-Fandino, Nicholas Woods, Rebekah Baskin, Anxhela Gjyshi, Alvaro N. Monteiro. SNP-FEMS: a method to identify DNA binding proteins interacting with enhancer elements. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 841. doi:10.1158/1538-7445.AM2015-841