Anti-XRCC1 monoclonal antibody, clone 34-3-6

Introduction: Increasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (15861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methods: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusion: Polymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14-8.40 and OR 3.29 95% CI 1.23-8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population. (C) 2018 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.

Peptidyl arginine deiminase, type II (PADI2) expression has been shown to potentiate multiple different carcinogenesis pathway including breast carcinoma and spontaneous skin neoplasia. The objective of this study was to examine the role of PADI2 in urothelial bladder cancer which has not been evaluated previously. Analysis of mutation and genome amplification of bladder cancer within The Cancer Genome Atlas (TCGA) showed that PADI2 is both mutated and amplified in a cohort of bladder cancer patients, with the largest number of mutations detected in urothelial bladder cancer. Even though PADI2 expression was not significantly correlated to survival in bladder cancer patients, it was significantly overexpressed at the mRNA and protein levels, as revealed by TCGA data and immunohistochemistry analysis, respectively. PADI2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. RNAi mediated silencing of PADI2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of PADI2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, PADI2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of PADI2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where PADI2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. PADI2 silencing did not affect proliferation rates and hence this would suggest that PADI2 knockdown is perhaps causing increased apoptosis as well as transition through the cell cycle, which needs to be confirmed in future studies. Our results reveal a yet undefined role of PADI2 as an oncogene in urothelial bladder cancer.