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Association Study Between Sensitivity To Chemotherapy Druy And Multidrug Resistance Genes In Colorectal Cancer

Posted on:2016-07-30Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2284330461469969Subject:Surgery
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Background and Objective:Malignant tumor has become the main diseases of harm to people’s health and life, including colorectal cancer in spectrum occupies the important position of malignancy, The incidence of these disease is increasing year every year.Surgery is the main treatment for colorectal cancer, but the effect of only operation is quite limited.Therefore, chemotherapy in the treatment of colorectal cancer has a more and more important position, but at the moment chemotherapy curative effect is still not ideal.Some research suggests that this may be related to the characteristics of the tumor, it is a polymorphism, heterogeneity and uneven cells group, these factors affect the effect of chemotherapy.With the deepening of the research of tumor, found the main reason is multidrug-resistant(multidrug hold, MDR), which mainly include GST-PI, P- gp, Topo-, TS and MRP.Improper chemotherapy not only can alleviate, could induce multi-drug resistance.Therefore, the realization of individualized chemotherapy, prevent the happening of the multi-resistant, by predicting the sensitivity of chemotherapy drugs to guide the clinical treatment, in order to improve the curative effect, has become a concern both at home and abroad.This study aims to by bioluminescence tumor in vitro susceptibility testing technology analysis of colorectal cancer cells to chemotherapy drugs commonly used 5- Fu, and oxaliplatin,Irinotecan for three single medicine and 5-Fu+ oxaliplatin,5-Fu+Irinotecan for the sensitivity of the two kinds of combination.By immunohistochemistry technique to detect colorectal cancer patients with multi-drug resistant gene expression product of GST- PI, TS and Topo II expression level, and to explore its correlation with the results of fungi susceptibility test in vitro.Methods:We selecte randomly from 2013 to 2014, luzhou medical college affiliated hospital surgical preoperative diagnosis of gastric cancer tissue in patients with colorectal cancer and peripheral venous blood,and use bioluminescence tumor in vitro susceptibility testing technology 5- Fu, and oxaliplatin,Irinotecan for three single medicine and 5-Fu+ oxaliplatin,5-Fu+Irinotecan for the sensitivity of the two kinds of combination of cancerous tissue, analyze the cancer tissue and peripheral blood lymphatic organization for more than the correlation of chemotherapeutic drugs sensitivity.Using immunohisto- chemistry technique to detect colorectal cancer tissues multi-resistant gene product GST- PI, the expression of TS and Topo II situation. Further analysis of tumor drug sensitivity and multi-resistant genes expression of correlation.Result:Colorectal cancer cells of 5- Fu, and oxaliplatin,Irinotecan for three single medicine and 5-Fu+ oxaliplatin,5-Fu+Irinotecan for the sensitivity of the two kinds of combination into vertical combination for kang 2 group were present a higher sensitivity, its no statistically significant difference(P > 0.05).Colorectal carcinoma patients peripheral blood lymphocyte of 5- Fu, and oxaliplatin,Irinotecan for three single medicine and 5-Fu+ oxaliplatin,5-Fu+Irinotecan for the sensitivity of the two kinds of combination,stand for two groups combination sensitive, its no statistically significant difference(P > 0.05).Colorectal cancer cells and peripheral blood lymphocytes of drugs between the inhibition rate, there exists a positive correlation, the relationship between the correlation coefficient at most is 0.92, the minimum is 0.61, and the correlation coefficient by significance test, there were statistically significant(P < 0.05).GST PI, Topo Ⅱand TS in the tissue of colorectal cancer expression rate is respectively: 80.0%, 56.6%, 46.6%.Each factor expression and the drug to the relationship between the inhibition rate in cancer cells, GST- PI expression in positive group OXA, 5- fu + OXA inhibition rate of cancer was lower than that in group negative expression(t=2.22、2.06,p=0.030、0.040);Topo II positive expression in the group, CPT- 11, 5- Fu + CPT- 11 inhibition rate of cancer was higher than that in group negative expression(t=2.53、-2.27,p=0.013、0.036);TS positive expression way, 5- Fu, 5- Fu + OXA, 5- Fu + CPT- 11 inhibition rate of cancer cells significantly reduced in the negative expression group(t=-2.24、2.23、2.54,p=0.023、0.037、0.023), but with CPT- 11 、OXA inhibition of cancer cell difference is not obvious(t=1.22、0.07,should try to choose combination, improve the sensitivity, reduce the resistance and the inhibition of lymphocyte foreign weeks. p=0.222、0.962).Conclusion:1.It may has some correlation between Drug sensitivity of the colorectal cancer tissue and peripheral blood lymphocytes.In the screening of chemotherapeutic drugs, should to the tumor tissue and peripheral blood lymphocytes for drug susceptibility testing at the same time, that make the screen of chemotherapy drugs on tumor cell has strong killing effect, and weak of peripheral blood lymphocyte inhibitory effect, avoid to choose strong killing effect on peripheral blood lymphocytes and tumor cells of weak inhibitory effect of chemotherapy drugs.At the same time, the drug sensitive test for difficult to get tumor tissue samples of patients, can be medicine sensitive experiment of peripheral blood lymphocytes to guide clinical drug use, and after a lot of chemotherapy in the treatment of patients develop resistance, drug sensitive test of peripheral blood lymphocytes may help clinical medication replacement drugs, reduce the patients’ resistance.2.High expression of GST- π to a certain extent, may associated with colorectal cancer tissue of OXA resistance;Colorectal cancer tissue resistance of CPT- 11 and Topo- II expression in cancerous tissue;TS may be 5- FU of drug targets;For clinical chemotherapy regimens in patients with colorectal, try to choose combination.3.In clinic, we choose to chemotherapy for colorectal cancer patients,...
Keywords/Search Tags:Colorectal cancer, chemotherapy, Chemosensitivity in vitro, Multidrug resistance
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