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CYP3A4Gene Polymorphisms Of Gastric Cancer Patients With Paclitaxel Sensitivity And TCM Syndrome Type Association Studies

Posted on:2014-02-28Degree:MasterType:Thesis
Country:ChinaCandidate:S Z ZhangFull Text:PDF
GTID:2234330395993082Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
Objective:Observe cytochrome P450metabolic enzymes CYP3A4gene polymorphism in patients with gastric cancer and paclitaxel sensitivity correlation; explore the TCM syndromes of the patients with gastric cancer and CYP3A4gene polymorphism correlation,provide preliminary reference for TCM Syndromes and paclitaxel sensitivity correlation.Methods:Collect94cases of advanced gastric cancer patients meet,determine the TCM syndrome type (disharmony of liver and stomach,spleen deficiency,sputum food stasis, blood deficiency).The number of disharmony of liver and stomach type is only4cases, it is to be removed.90patients meet inclusion criteria, peripheral venous blood collected before chemotherapy, extracted leukocyte DNA, determine the sequence and structure of the target gene CYP3A4from the database,design primers for PCR amplification, Applicate DHPLC technology to detect gene polymorphism, observe the efficacy of paclitaxel-based combination chemotherapy regimens,record CYP3A4polymorphisms, paclitaxel sensitivity; use statistical methods analyze the correlation between the CYP3A4polymorphisms with paclitaxel sensitivity and TCM syndromes.Results:DHPLC screening PCR product, doublet is defined as the mutant-type, single peak is defined as the wild-type.DHPLC detection is bimodal and unimodal specimens sequencing, G→A substitution mutation occurs on exon10of the CYP3A4gene198bp.Paclitaxel sensitivity between wild-type and mutant-type are statistically significant different (P<0.05). Enroll a total of90patients with advanced gastric cancer,37cases of spleen deficiency type (41.11%),40cases of sputum food stasis type(44.45%),13cases of blood deficiency type (14.44%).The spleen deficiency type or sputum food stasis type is more than the blood deficiency type.There are difference between different TCM syndromes in patients with advanced gastric cancer CYP3A4gene polymorphism.Compare the spleen deficiency type and blood deficiency type,P=0.035<0.05,statistically different;compare the sputum food stasis type and blood deficiency type,P=0.04<0.05,statistically different;compare the spleen deficiency type and sputum food stasis type,P=0.92>0.05,have no difference.CYP3A4gene polymorphisms in advanced gastric cancer patients with different TCM syndromes is related to the paclitaxel efficacy. The spleen deficiency type and sputum food stasis type are statistically significant(P<0.05), the blood deficiency type isn’t statistically significant (P>0.05).Conclusions:Analyzed:1.On the exon10of the CYP3A4gene in patients with gastric cancer detected198bp G→A substitution mutation;2.paclitaxel sensitivity is related to the CYP3A4gene polymorphism in patients with gastric cancer;3.different TCM syndromes in patients with advanced gastric cancer CYP3A4gene polymorphism have differences, the CYP3A4gene mutation in the spleen deficiency and sputum food stasis types are easier than the blood deficiency type, there is no significant difference between the spleen deficiency and sputum food stasis types;4.different TCM syndromes in patients with advanced gastric cancer patients with different CYP3A4genotype exist differences in ensitivity to paclitaxel, the pleen deficiency and sputum food stasis types of the CYP3A4gene polymorphism in patients with advanced gastric cancer is related to paclitaxel sensitivity, the blood deficiency of the CYP3A4gene polymorphism in patients with advanced gastric cancer isn’t related to paclitaxel sensitivity.
Keywords/Search Tags:Gastric cancer, CYP3A4, Paclitaxel, TCM syndrome type
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