ABSTRACT
To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.
Subject(s)
Animals , Male , Rats , Cytochrome P-450 Enzyme System , Metabolism , Drugs, Chinese Herbal , Pharmacology , Injections , Isoenzymes , Metabolism , Microsomes, Liver , Rats, Sprague-DawleyABSTRACT
<p><b>BACKGROUND</b>Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/ MDR1 C3435T single-nucleotide polymorphism (SNP).</p><p><b>METHODS</b>Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment.</p><p><b>RESULTS</b>A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 C118T, test for heterogeneity was done (χ(2) = 13.41, P = 0.1), and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09 - 2.06, P = 0.01). In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done (χ(2) = 3.22, P = 0.36), and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44 - 3.68, P = 0.0005).</p><p><b>CONCLUSIONS</b>The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , DNA-Binding Proteins , Genetics , Endonucleases , Genetics , Lung Neoplasms , Drug Therapy , Genetics , Platinum , Therapeutic Uses , Polymorphism, Genetic , GeneticsABSTRACT
Objective To discuss human papilloma virus(HPV)prevalence and HPV genotypes distribution and the infection factors,to provide scientific guidance for the prevention and treatment of cervical cancer.Methods From March to November in 2009,605 women received cervical HPV testing in the Tumor Hospital of Harbin Medical University,to obtain specimens of cervical cytology,rapid flow-through hybridization technique (namely Hybribio flow-through hybridization)was used to detect HPV genotypes simultaneously.Single-factor and multivariate factors non-conditional Logistic regression analytic method was used to discuss the relationship between HPV infection of females and age,marital condition,level of education,level of income,occupation,initial age for sex,contraception,number of pregnancies,delivery approach and smoking.Results HPV infection rate was 21.49%(130/605),the positive rate of HPV infection in high-risk subtypes was 15.70%(95/605),the most common type was 5.29%(32/605)in the samples.Single factor non-conditional logistic regression model analysis showed that initial age for sex was the risk factor(X2=4.4618,P<0.05),HPV prevalence increased with a lower initial age for.sex reduced.But there was no significant difference in age,marital condition,education,income,occupation,contraception,number of pregnancy,delivery approach and smoking teams(X2=0.0525,1.8510,1.0348,0.2592,1.1176,1.5664,2.8835,1.4597,2.6161,all P>0.05).The analysis of multivariate factors nonconditional Logistic regression showed that the age of initially having sex,marital status and number of pregnancies were the risk factors(X2=21.6637,8.0574,15.7573,all P<0.05).Conclusions The risk factors for HPV infection are mainly about having sex too young,marital status and number of pregnancies,attention should be paid to screening for HPV.