Mouse anti-Human XRCC3 monoclonal antibody, clone 21G27

Background/Aims: We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. Methodology: A total of 150 cases and 158 controls were selected from May 2008 to May 2010. XRCC1-Arg399Gln and XRCC3-Thr241Met polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. All analysis was performed by using the STATA statistical package. Results: A significant increased risk of HCC was associated with XRCC1 399Arg/Gln, and a heavy risk of HCC was also found in individuals with XRCC3 241Met/Met genotypes. A significant association was found between positive HBsAg and Arg/Gln. XRCC3 Thr/Met genotypes had a significant positive association with HBsAg (+) and a heavy risk of HCC was found in HBsAg (+) individuals with XRCC3 Met/Met genotype. Individuals carrying XRCC1 Gln/Gln genotypes showed significantly lower median survival than XRCC1 Arg/Arg genotypes and significant hazard ratio (HR=1.38, 95% CI=1.04-1.84) was found. Meanwhile, we found a moderate HR for XRCC3 Thr/Met (HR=1.96, 95% CI=1.23-3.15) and a heavy HR for XRCC3 Met/Met (HR=2.98, 95% CI=1.77-7.54). Conclusions: In conclusion, we observed that XRCC1-Arg399Gln and XRCC3-Thr241Met polymorphism is associated with susceptibility to HCC and XRCC1 Gln allele and XRCC3 Met allele genotype showed significant poor prognosis of HCC.

Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (>= 24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage. Using gamma-H2AX as a measurement of DNA damage in MCF-7 breast cancer cells, we demonstrate that 10 or 80 nM dFdCyd alone produced significantly more late DNA damage compared to that observed within 4 h after treatment. The combination of dFdCyd treatment followed by irradiation did not produce a consistent increase in DNA damage in the first 4 h after treatment, however, there was a synergistic increase 24-48 h later relative to treatment with dFdCyd or radiation alone. RNAi suppression of the essential HRR protein, XRCC3, significantly decreased both radiosensitization and late DNA damage. Furthermore, inhibition of HRR with the Rad51 inhibitor B02 prevented radiosensitization when added after, but not during, treatment with dFdCyd and radiation. To our knowledge, this is the first published study to show that radiosensitization with dFdCyd results from a synergistic increase in DNA damage at 24-48 h after drug and radiation treatment, and that this damage and radiosensitization require HRR. These results suggest that tumors that overexpress HRR will be more vulnerable to chemoradiotherapy, and treatments that increase HRR and/or mismatches in DNA will enhance dFdCyd radiosensitization. (C) 2016 by Radiation Research Society