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OBJECTIVE:To systematically evaluate the relationship of multi-drug resistance gene MDR1 C3435T gene polymor-phism with therapeutic efficacy of proton pump inhibitors (PPIs)-based triple therapy for Helicobacter pylori eradication. METH-ODS:Retrieved from PubMed,EMBbase,CBM,CJFD,Wanfang database and VIP,clinical studies about MDR1 C3435T gene polymorphism and PPIs-based triple therapy for the eradication of H. pylori infection were collected. Meta-analysis was performed by using Rev Man 5.3 statistical software after data extraction and quality evaluation by using STREGA statement. RESULTS:A to-tal of 7 studies were included,involving 1019 patients. The results of MDR1 C3435T genotyping in patients were classified as wild homozygote genotype(CC),mutant heterozygous genotype(CT)and mutant homozygote genotype(TT). The results of Me-ta-analysis showed that there was no statistical significance in the eradication rate of H. pylori among CC,CT and TT groups of MDR1 C3435T gene polymorphism [CC vs. CT:OR=0.99,95%CI(0.69,1.42) ,P=0.95;CC vs.TT:OR=1.44,95%CI(0.66, 3.15),P=0.36;CT vs.TT:OR=1.54,95%CI(0.86,2.73),P=0.14]. Subgroup analysis showed the eradication rate of H. pylori in CT genotype group was higher than that in TT genotype group among Asian population [OR=2.35,95%CI(1.53,3.62),P<0.001]. CONCLUSIONS:MDR1 C3435T gene polymorphism basically do not affect therapeutic efficacy of PPIs-based triple thera-py for H. pylori eradication. For Asian population,gene detection is useful for the treatment.
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Ciclosporin A (CsA). an immunosuppressive macrolide antibiotics, is widely applied to prevent rejections after organ transplants. CsA is mainly transported by P-glycoprotein (P-gp) and metabolized by cytochrome P450 (CYP450) 3A.Genetic polymorphisms of CYP3A and MDRl probably influence the expressions and bioactivity of CYP3A and P-gp.and may affect the pharmacokinetics of CsA.This issue summarizes the correlation between genetic polymorphisms of CYP3A and MDRl and the pharmacokinetics of CsA to guide the rational and individualized medication.
ABSTRACT
Ciclosporin A (CsA), an immunosuppressive macrolide antibiotics, is widely applied to prevent rejections after organ transplants. CsA is mainly transported by P-glycoprotein (P-gp) and metabolized by cytochrome P450 (CYP450) 3A.Genetic polymorphisms of CYP3A and MDR1 probably influence the expressions and bioactivity of CYP3A and P-gp,and may affect the pharmacokinetics of CsA.This issue summarizes the correlation between genetic polymorphisms of CYP3A and MDR1 and the pharmacokinetics of CsA to guide the rational and individualized medication.
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Objective To study the significance of combined detection of lung resistance protein(LRP),P-glycoprotein(P-gp),glutathione S-transferace-?(GST-?) and topoisomeraseⅡ(TopoⅡ) in gastric cancer prognosis judgment.Methods One hundred and thirty-six patients with human gastric carcinomas were studied for the expression of LRP,P-gp,GST-?and TopoⅡ by using immunohistochemistry.Results There were significant relationships in the positive expression rate of LRP,P-gp,GST-?between high-Medium differentiated adenocarcinoma and Poorly differentiated adenocarcinoma,Mucinous carcinoma,and Undifferentiated carcinoma(P
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Objective To study the effects of survivin antisense RNA on SGC7901 cell’s apoptosis and chemosensitivity to taxotere, and to investigate its effect on the expression of multi-drug resistance gene-1 (MDR-1). Methods Survivin antisense eukaryotic vector anti-pcDNA3-svv was transfected into SGC7901 cell lines by lipofectamine and positive clones were screened out then. Survivin protein and MDR-1 mRNA were measured by western blot and RT-PCR, respectively. Apoptosis that was induced by anti-pcDNA3-svv was observed by electronic microscope, and the sensitivity of SGC7901 cell to taxotere was examined by MTT. Results The expressions of survivin protein and MDR-1 mRNA in transfected SGC7901 cells both decreased more significantly than that of non-transfected cells (P
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Objective To establish a method of competitive polymerase chain reaction combined with restrictive endonucleases to measure the methylation quantitatively in MDR1 promoter region.Methods One sense primer and two anti-sense primers were designed to amplify a fragment of MDR1 gene promoter region, which was located between -102 and +186 bp containing a methylation site. The internal reference DNA fragment, witch was less 30bp than target fragment was made by three times of polymerase chain reaction(PCR)using different anti-sense primer and then subcloned into the Pbluescriptsk+ plasmid. The genomic DNA digested by Hpa, a methylation-sensitive restrictive endonuclease and competitive internal reference DNA were competitively amplified for MDR1 promoter in the same tube by PCR. The PCR products were electrophoresed on agarose gel, stained by ethidium bromide and subjected to image analysis scanner. The amount of target fragment was calculated as following, the optical density ratio of target fragment to competitive internal reference fragment multiplied the amount of competitive internal reference DNA. The ratio of PCR products amplified from HpaⅡ digested DNA and undigested DNA was named the methylation rate.Results The genomic DNA serially diluted with optimal amount of competitive internal reference DNA were co-amplified for MDR1 promoter. The significant positive correlation between the ratio of two products and the amount of genomic DNA was demonstrated. The correlation coefficient was 0.992, P