Browsing by Author "Chen, Y. T."
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Item Open Access Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C > T polymorphism in non-small cell lung carcinoma(BioMed Central, 2013) Senses, K. M.; Gonen, M.; Barutcu, A. R.; Kalaylioglu, Z.; Isbilen, M.; Konu, O.; Chen, Y. T.; Altorki, N. K.; Gure, A. O.Background: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.Methods: Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP.Results: We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders.Conclusions: Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function. © 2013 Senses et al.; licensee BioMed Central Ltd.Item Open Access Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues(Wiley, 2012) Nissan, A.; Stojadinovic, A.; Rosenbaum, S. M.; Halle, D.; Grinbaum, R.; Roistacher, M.; Bochem, A.; Dayanc, B. E.; Ritter, G.; Gomceli, I.; Bostanci, E. B.; Akoglu, M.; Chen, Y. T.; Old, L. J.; Gure, A. O.Early detection of colorectal cancer (CRC) is currently based on fecal occult blood testing (FOBT) and colonoscopy, both which can significantly reduce CRC-related mortality. However, FOBT has low-sensitivity and specificity, whereas colonoscopy is labor- and cost-intensive. Therefore, the discovery of novel biomarkers that can be used for improved CRC screening, diagnosis, staging and as targets for novel therapies is of utmost importance. To identify novel CRC biomarkers we utilized representational difference analysis (RDA) and characterized a colon cancer associated transcript (CCAT1), demonstrating consistently strong expression in adenocarcinoma of the colon, while being largely undetectable in normal human tissues (p < 000.1). CCAT1 levels in CRC are on average 235-fold higher than those found in normal mucosa. Importantly, CCAT1 is strongly expressed in tissues representing the early phase of tumorigenesis: in adenomatous polyps and in tumor-proximal colonic epithelium, as well as in later stages of the disease (liver metastasis, for example). In CRC-associated lymph nodes, CCAT1 overexpression is detectable in all H&E positive, and 40.0% of H&E and immunohistochemistry negative lymph nodes, suggesting very high sensitivity. CCAT1 is also overexpressed in 40.0% of peripheral blood samples of patients with CRC but not in healthy controls. CCAT1 is therefore a highly specific and readily detectable marker for CRC and tumor-associated tissues. Copyright © 2011 UICC.Item Open Access NY-BR-1 is a differentiation antigen of the mammary gland(Lippincott Williams & Wilkins, 2007-03) Jager, D.; Filonenko, V.; Gout, I.; Frosina, D.; Eastlake-Wade, S.; Castelli, S.; Varga, Z.; Moch, H.; Chen, Y. T.; Busam, K. J.; Seil, I.; Old, L. J.; Nissan, A.; Frei, C.; Gure, A. O.; Knuth, A.; Jungbluth, A. A.NY-BR-1 was recently identified by autologous serological typing of the recombinant expression library in a breast cancer patient. Extensive reverse transcriptase-polymerase chain reaction analysis revealed the presence of NY-BR-1 in normal breast tissue and tumors derived thereof. Except normal testis, no other normal tissue or tumors showed NY-BR-1 expression. However, nothing is known about the expression of its actual antigen. In the present study, we describe the generation of 2 new monoclonal antibodies, NY-BR-1#2 and NY-BR-1#3, to NY-BR-1 for the analysis of its expression on a protein level employing recombinant NY-BR-1 protein for the immunization of BALB/c mice. In normal tissues, immunohistochemical testing demonstrates NY-BR-1 in a mostly focal fashion in the epithelia of ducts and acini of the mammary gland. No other tissue was immunopositive including testis. In tumors, homogenous staining can be seen in almost all ductal carcinomas in situ and/or the intraductal component of invasive carcinomas. Invasive carcinomas show a lower number of NY-BR-1-positive tumors. Initial higher numbers of NY-BR-1 mRNA-positive invasive carcinomas are most likely based on sample error owing to the contamination of tumor tissue with remnants of normal breast epithelium. Sweat gland carcinomas, which are related to breast cancer, are also positive in about one-third of the cases. These data indicate that NY-BR-1 is a differentiation antigen of the mammary gland that could be useful for diagnosis and/or immunotherapy of breast carcinomas.