Incidence of fibroblast growth factor receptor 3 gene (FGFR3) A248C, S249C, G372C, and T375C mutations in bladder cancer

Bladder cancer is the most frequent cancer of the urinary system. Fibroblast growth factor receptors (FGFR) belong to the tyrosine kinase family and have important roles in cell differentiation and proliferation and embryogenesis. FGFR3 is located on chromosome 4p16.3, and missense mutations of FGFR3 are associated with autosomal dominant human skeletal disorders and have some oncogenic effects. We examined the incidence of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, and their correlation with clinical-pathological parameters in bladder carcinoma patients. Fifty-six paraffin-embedded specimens of transitional cell carcinoma of the urinary bladder were included in this study. Analysis of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, was performed by PCR- restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, were detected in 33 of the 56 patients (heterozygous mutant). Among the 56 transitional cell carcinomas, missense point mutations were detected in seven of them at codon A248C, 28 of them at codon S249C, and three of them at codon T375C, similar to data from previous reports. When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade. © FUNPEC-RP

The sulfite molecule enhances homocysteine toxicity in SH-SY5Y cells

Homocysteine (hcy) is an amino acid that contains sulfur species. In healthy individuals, plasma hcy levels are low. The aim of this study was to investigate the potential neurotoxic effects of hcy and sulfite (sft) molecules alone and in their combination, and also to identify the relationship of these substances on oxidative stress. SH-SY5Y cells were used as an invitro neurodegenerative disease model. The SH-SY5Y cells were treated with various concentrations of hcy alone, sft alone (final concentrations in the well were 10–250 µM and 0.1–5 mM, respectively) and a combination of both (hcy + sft). Their cytotoxicity and genotoxic effects were investigated using the XTT test and Comet assay and, their impact on oxidative stress was examined using total antioxidant–oxidant status (TAS-TOS) kits. The highest toxic doses of hcy and sft were found to be 250 μM and 5 mM, respectively, but the maximum toxic effect was observed for hcy + sft (p < 0.001). In addition, an increase in DNA damage was evident in all groups, but maximal damage was inflicted using in hcy + sft (p < 0.001). The oxidative stress index was significantly increased in hcy + sft (p < 0.05). Determining the increase in sft and hcy levels may contribute to delaying the occurrence of diseases before symptoms of neurodegenerative disease appear. © 2019, Springer Nature B.V

A novel oncogene URG4/URGCP and its role in cancer

Oncogenes are mutated form of normal cellular genes called as proto-oncogenes and conduce to the cancer development process. Despite the fact that so many genes have been described, new genes with oncogenic characteristic and potential or tumor supressoring activity are still being defined. Recently, Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP), a novel gene, induced by hepatitis-Bvirus-encoded X antigen (HBxAg), has been identified. URG4/URGCP gene was registered to the National Center for Biotechnology Information-GenBank (NCBI-GenBank, Entrez Genelp: 55665 and Entrez Nucleotide ID NM_017920). URG4/URGCP is located on the short arm of chromosome 7 (7p13) and synthesizes a protein containing 922 amino acids in the cytoplas. Relationship between URG4/URGCP expression and clinicopathologic characteristics were evaluated and significant results were in various cancer types such as hepatocellular carcinoma, osteosarcoma, nasopharyngeal carcinoma, bladder cancer, gastric cancer and glioma. Although, biological activity of URG4/URGCP and its effect mechanism in malignant cells is not fully understood, all interesting and promising results shows that URG4/URGCP may be a putative oncogene that contributes to multistep carcinogenesis, cell cycle regulation and other important biological process in the cell

efficiencies in patients with schizophrenia and schizoaffective disorder

Schizophrenia and schizoaffective disorder are chronic and debilitating psychiatric disorders. The present study was designed to determine DNA damage in patients with schizophrenia and schizoaffective disorder to assess the roles of oxidative metabolism and DNA repair mechanisms in this process, to assess the contribution of drugs, and thus to demonstrate the differences between schizophrenia and schizoaffective disorder. Thirty schizophrenia and 30 schizoaffective disorder patients, each having at least five years of disease history, aged between 18 and 60 years with no physical or neurological diseases, and 30 healthy volunteers participated in the study. Psychometric scales were applied, and 5 ml of blood was taken from all participants. The DNA damage was measured in lymphocytes by the comet assay method; the total oxidative parameters by ELISA; OGG1 and NEIL1 gene expressions by real-time PCR: and the role of drugs by in vitro assays. The most important finding in this study was that patients with schizophrenia had significantly greater DNA damage than schizoaffective disorder patients and the controls. This study also provides evidence of high oxidative stress statuses and inadequate DNA repair capacities in patients with schizophrenia. Moreover, psychotropic drugs did not induce any DNA damage to the lymphocytes according to in vitro analyses. The use of clozapine and adequate repair processes of the patients were the decisive factors in the prevention of DNA damage. The results of this study provide a reexamination of schizoaffective disorder within the schizophrenia spectrum and indicate that schizoaffective disorder may be considered a different diagnostic category. (C) 2018 Elsevier B.V. All rights reserved