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Wang T.,Tuberculosis Research Institute | Yu H.T.,Tuberculosis Research Institute | Wang W.,Tuberculosis Research Institute | Pan Y.Y.,Fuzhou Peoples Liberation Army General Hospital | And 2 more authors.
Journal of International Medical Research | Year: 2010

This study was designed to investigate the association of genetic polymorphisms of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1 (GSTM1) with susceptibility to antituberculosis drug-induced hepato-toxicity (ADIH) in Chinese tuberculosis patients. All patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Genomic DNA from 104 patients with ADIH and 111 without ADIH was analysed for the frequency of CYP2E1 RsaI and GSTM1 RsaI genotypes by polymerase chain reaction and restriction fragment length polymorphism. The association of polymorphisms with susceptibility to ADIH was calculated using the χ2-test and logistic regression analysis. The CYP2E1 RsaI polymorphisms were significantly associated with ADIH and the c1/c1 genotype was an independent risk factor for ADIH. Compared with the GSTM1 RsaI present genotype, the GSTM1 RsaI null genotype tended to increase susceptibility to ADIH, but the association with ADIH was not significant. The results indicate that CYP2E1 RsaI genotype c1/c1 is a potential risk factor for ADIH in the Chinese population. The tendency of the GSTM1 RsaI null genotype to increase susceptibility to ADIH needs further study. © 2010 Field House Publishing LLP. Source

Wu L.,Tuberculosis Research Institute | Wang J.,Tuberculosis Research Institute | Wang Q.,Tuberculosis Research Institute | Jia D.,Tuberculosis Research Institute | Liang J.,Tuberculosis Research Institute
Chinese Journal of Lung Cancer | Year: 2011

Background and objective Survivin is a member of the inhibitor of apoptosis family of proteins. The Survivin protein is highly expressed in most human tumors, but it is completely absent in terminally differentiated cells. Consequently, Survivin is an ideal target for cancer therapy because cancer cells are targeted and normal cells are left alone. The aim of this study is to construct a lentivirus-shRNA vector, and to disrupt the expression of Survivin in A549 cells. The effect of sh-RNA Survivin on A549 cells was analyzed. Methods Target DNA sequences of Survivin shRNA were designed to obtain recombinant plasmids. After the plasmids were transfected into 293T cells, the virus was collected. Hela cells were used to detect the virus titer. Survivin mRNA and protein expression in the infected A549 cells were detected via reverse transcription polymerase chain reaction and Western blot analysis. The proliferation of A549 cells were detected via 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide and flow cytometry assays. Results The recombinants were successfully constructed, and Survivin expression was inhibited. The cells were blocked at the G 2/M phase. Conclusion Recombinant lentivirus with shRNA targeting Survivin was successfully constructed. The lentivirus can down-regulate Survivin expression in A549 cells as well as inhibit proliferation, and is hence a potential gene therapy for lung cancer. Source

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