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    Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression
    (C M B ASSOC, 34 BOULEVARD SOLFERINO, 86000 POITIERS, FRANCE, 2019) Küçük, Nazlı Ezgi Özkan; Horozoğlu, Cem; Timirci Kahraman, Özlem; Arıkan, Soykan; Farooqi, Ammad Ahmad; Sürmen, Saime; Korkmaz, Gurbet; Kelten Talu, Esra Canan; Sabitaliyevich, Uteuliyev Yerzhan; Yaylım, İlhan
    Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with beta-catenin to fuel colorectal cancer development and progression. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p-0.031). 'MT haplotype was found to be statistically higher in CRC compared to the control group (p-0.007). Mere was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.
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    LGALS3 and AXIN1 gene variants playing role in the Wnt/?-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer
    (Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2016) Korkmaz, Gurbet; Horozoglu, Cem; Arikan, Soykan; Gural, Zeynep; Saglam, Esra Kaytan; Turan, Saime; Ozkan, Nazli Ezgi
    The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/beta-catenin pathway by binding to beta-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the beta-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS(3) gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9 +/- 0.69 ng/ml vs. 0.79 +/- 0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/beta-catenin pathway in the pathogenesis of colorectal cancer.