The role of XRCC6/Ku70 in nasopharyngeal carcinoma.

The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively. With regard to the XRCC6 promoter T-991C, the TC and CC genotypes were associated with a significantly increased risk of NPC compared with wild-type TT genotype (adjusted odds ratio 2.02 and 3.42, 95% confidence interval 1.21-3.32 and 1.28-8.94, P=0.0072 and 0.0165, respectively). The mRNA and protein expression levels for NPC tissues revealed significantly lower XRCC6 mRNA and protein expression in the NPC samples with TC/CC genotypes compared to those with the TT genotype (P=0.0210 and 0.0164, respectively). These findings suggest that XRCC6 may play an important role in the carcinogenesis of NPC and could serve as a chemotherapeutic target for personalized medicine and therapy.

Electroacupuncture and Acupuncture Promote the Rat's Transected Median Nerve Regeneration.

Background. Acupuncture and electroacupuncture treatments of damaged nerves may aid nerve regeneration related to hindlimb function, but the effects on the forelimb-related median nerve were not known. Methods. A gap was made in the median nerve of each rat by suturing the stumps into silicone rubber tubes. The influences of acupuncture and electroacupuncture treatments on transected median nerve regeneration were evaluated from morphological, electrophysiological, and functional angles. Results. Morphologically, the group receiving acupuncture and electroacupuncture treatments had larger total nerve area and blood vessel number compared with the controls. Electrophysiologically, the group receiving electroacupuncture had significantly larger amplitude and larger area of the evoked muscle action potentials compared with the controls. Functionally, the acupuncture and electroacupuncture treatments enhanced the injured paw's ability to regain its grasping power and resulted in a faster efficiency to a new bilateral balance. Conclusion. Our findings provide multiapproach evidence of the efficacy of acupuncture and electroacupuncture treatments to the regeneration of median nerve. Indeed, acupuncture and electroacupuncture appear to have positive effects on the regeneration processes. This platform is beneficial to further study the clinical application of acupuncture and electroacupuncture alternative treatments on nerve-injured patients.

Impact of neck dissection in early tongue and buccal cancer without neck extension.

PROBLEM: The role of elective neck dissection in early stage tongue and buccal squamous cell carcinoma with negative neck lymph nodes is still controversial. METHODS: We retrospectively reviewed patients with T1-2N0M0 buccal and tongue cancer who underwent primary tumour excision with or without elective neck dissection between January 1997 and December 2006. RESULTS: Elective neck dissection specifically improved disease-free survival of T2N0M0 buccal cancer and overall survival of T2N0M0 tongue cancer. CONCLUSION: Elective neck dissection seems to improve the disease-free survival rate of T2N0M0 buccal cancer and the overall survival rate of T2N0M0 tongue cancer but has no beneficial effect on the survival rate of T1N0M0 buccal and tongue cancer.

The involvement of insulin receptor genotypes in pre- and co-obese acanthosis Nigricans children and adolescent.

Acanthosis nigricans (AN) is most commonly related to obesity as a manifestation of cutaneous insulin resistance in children and adolescents, while the interaction and time course between AN and obesity and detailed mechanism for the pre- and co-obese appearance of AN (PCOAN) in child are unclear. In this study, the involvement of insulin receptor in child PCOAN was investigated via studying the association of polymorphisms of INSR gene with PCOAN. In total, 99 children with PCOAN and 100 healthy controls recruited were genotyped and analyzed by PCR-RFLP method. Significantly different distributions were found in the frequency of the INSR His1085His genotypes, but not in other INSR genotypes, between the two groups. Our results provide not only the evidence that the T allele of INSR His1085His is correlated with the appearance of PCOAN but revealed that the insulin receptor pathway may play an important role in this PCOAN.

Evaluation of transforming growth factor and vascular endothelial growth factor polymorphisms in Taiwan Chinese patients with pterygium.

PURPOSE: Pterygium is an invasive and highly vascularized growth, thought to arise from activated and proliferating limbal epithelial stem cells. Epidemiologic studies have found the increase of active angiogenic and epithelial growth factors in pterygia, and implicated that these molecules could be involved directly or indirectly in the pathogenesis of pterygia as causative factors. The aim of this study was to investigate the association of polymorphisms of transforming growth factor (TGF) and vascular endothelial growth factor (VEGF) with pterygium. METHODS: A total of 133 pterygium patients and 105 volunteers without pterygium were enrolled in this study. Polymerase chain reaction based restriction fragment length polymorphism analysis was used to resolve the TGF-Beta1-509 and VEGF-460 genotypes. RESULTS: There was no significant difference in the allele frequency or genotype of TGF-Beta1-509 or VEGF-460 between total pterygium and the control group. No interaction between TGF-Beta1-509 and VEGF-460 was found either. CONCLUSIONS: These results indicate that TGF-Beta1-509 and VEGF-460 polymorphisms were not highly associated with the pathology of pterygium. However, it may still be worthwhile to continue to search for angiogenic gene polymorphisms in order to predict the development of pterygium.

Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells.

Arsenic is generally recognized as a nonmutagenic carcinogen because sodium arsenite induces DNA damage only at very high concentrations. In this study we demonstrate that arsenite concentrations above 0.25 microM induce DNA strand breaks in both human leukemia cells and Chinese hamster ovary cells. Therefore, DNA damage may be involved in arsenic-induced carcinogenesis. Formamidopyrimidine-DNA glycosylase and proteinase K greatly increased DNA strand breaks in arsenite-treated cells, providing evidence that a large portion of arsenite-induced DNA strand breaks come from excision of oxidative DNA adducts and DNA-protein cross-links. Because DNA strand breaks appear only temporarily during excision repair, the level of detectable DNA strand breaks will be low at any given time point. For this reason many previous studies have only detected low levels of DNA strand breaks. We also show that catalase, and inhibitors of calcium, nitric oxide synthase, superoxide dismutase, and myeloperoxidase, could modulate arsenite-induced DNA damage. We conclude that arsenite induces DNA adducts through calcium-mediated production of peroxynitrite, hypochlorous acid, and hydroxyl radicals.

Nitric oxide is involved in arsenite inhibition of pyrimidine dimer excision.

Arsenite is a human carcinogen reported to inhibit DNA repair. The binding of arsenite to functional thiol groups of DNA repair enzymes has in the past been suggested as a possible mechanism for the effect of arsenite on DNA repair. However, recent studies indicate that reactive oxygen species and nitric oxide are involved in arsenite toxicity. This research aims to elucidate the role of these possible mechanisms in the inhibition of UV-induced DNA repair by arsenite. As arsenite inhibits UV-DNA repair in Chinese hamster ovary cells, and this is a commonly used cell line for UV repair experiments, we used these cells to examine the effect of arsenite on the expression of UV-irradiated reporter genes. The T4 UV endonuclease V-incorporated comet assay was used to examine specifically the effect of arsenite on pyrimidine dimer excision. We showed that inhibition of UV-DNA repair by arsenite was suppressed by nitric oxide synthase inhibitors. Arsenite increased nitric oxide production and nitric oxide generators inhibited UV-DNA repair. The involvement of nitric oxide in the inhibition of pyrimidine dimer excision by arsenite was also confirmed in human fibroblasts. Investigation into the effect of oxidant modulators did not give a clear indication that reactive oxygen species are involved in arsenite inhibition of UV-DNA repair. Phenylarsine oxide, a strong thiol-reacting agent, did not inhibit pyrimidine dimer excision and also did not increase nitric oxide production. Our results show conclusively that nitric oxide is involved in the inhibition of pyrimidine dimer excision by arsenite. Reactive oxygen species and the binding of arsenite to functional thiol groups of DNA repair enzymes do not appear to be involved.

Dithiothreitol enhances arsenic trioxide-induced apoptosis in NB4 cells.

Recently, arsenic trioxide (As2O3) was reported to induce clinical remission in patients with acute promyelocytic leukemia. Modulation of protein phosphorylation by binding to the vicinal thiols has been suggested as a possible mechanism. We found that phenylarsine oxide, a strong vicinal thiol-binding agent, neither induced nuclear fragmentation or DNA laddering nor increased caspase activity in NB4 cells; however, As2O3 and a weak thiol-binding agent, dimethylarsinic acid, did increase activity. Dithiothreitol (DTT) effectively suppressed the phenylarsine oxide-inhibited cellular reductive capacity, but unexpectedly, enhanced As2O3-induced apoptosis in NB4 cells. As2O3-induced and As2O3-plus-DTT-induced apoptosis in NB4 cells was modulated by oxidant modifiers, but not by nitric oxide synthase inhibitors. These results demonstrate that DTT, a dithiol agent and known antidote for trivalent inorganic arsenic, enhances the toxicity of As2O3, thereby opening a new research direction for the mechanisms of arsenic toxicity and perhaps also helping in the development of new therapeutic strategies for treating leukemias.