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Relation Between The Expression Of TP And OPRT In Colorectal Cancer And The Sensitivity Of S-1

Posted on:2012-08-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y SiFull Text:PDF
GTID:2154330332496318Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Objective:1 To provide theory guidance for designing and optinicing clinical chemotherapy scheme and practice individualization chemotherapy, we established stable colorectal carcinoma vitro primary culture model and carried out vitro chemosensitive experiment by the MTT assay.2 To observe the expression of thymidine phosphorylase(TP) and orotate phosphoribosyl transferase (OPRT) in colorectal carcinoma,normal tissues and corresponding lymph node metastases, and explore the clinical pathological significance of TP and OPRT.3 We explored the expression of TP and OPRT in colorectal carcinoma and corresponding lymph node metastases and their relations with sensitivity of S-1 chemotherapy, analyzed the relationship between the two genes expression and tumor drug sensitivity test in vitro, and assessed the feasibility of TP and OPRT as S-1 sensitivity indicators of chemotherapy.Methods:We proceeded the S-1 drug sensitibility test in vitro culture with MTT method in 42cases of fresh specimens of colorectal cancer, and measured the drug sensitivity and resistance to S-1 in different individuals.We also observed the expression of TP and OPRT in 42 cases of colorectal cancer,normal tissues and 9 cases of metastatic lymph node tissues by immunohistochemical method,and analyzed the statistical correlation between their expression and the corresponding resistance to chemotherapy, and evaluated thei relevance betwween the expression of the two genes and S-1 sensitivity.Results:1 MTT assay results show that in 42 cases of cancer tissues, the sensitivity of S-1 was 33.3% (14/42), the sensitivity of poorly differentiated adenocarcinoma group (58.3%) was higher than high and moderately differentiated adenocarcinoma group (23.3%) (P<0.05), the sensitivity in lymph node metastasis group (66.7%)was higher than in without lymph node metastasis(24.2%) (P<0.05), There was no significant differences between with age, sex, histological grade in sensitivity(P>0.05).2 The expression of TP in 42 cases of colorectal cancer(24.7%) was significantly higher than normal colorectal mucosa tissue (0%) (P<0.05). The rate of TP expression in poorly differentiated adenocarcinoma group (58.3%) significantly higher than high and moderately differentiated adenocarcinoma group (10%) (P<0.05). The rate of TP expression (66.7%) in lymph node metastasis group was significantly higher than that without lymph node metastasis group (12.1%) (P<0.05). T.The strong positive expression of TP in group of late Duck's stage was high (P<0.05).There were no significant differences between TP expression in colorectal cancer with age, sex, and histological grade (P> 0.05).3 The expression of OPRT in 42 cases of colorectal cancer(52.3%) was significantly higher than normal colorectal mucosa tissue (4.5%) (P<0.05).The rate of OPRT expression (77.8%) in lymph node metastasis group was significantly higher than that without lymph node metastasis group (45.4%) (P<0.05).The positive rate of OPRT in group of late Duck's was high (P <0.05).There were no significant differences between OPRT expression in colorectal cancer with age, sex, differentiation degree and histological grade(P> 0.05).4 The TP and OPRT expression in the 9 cases of colorectal cancer with metastatic lymph nodes were significantly higher than that in the primary tumor, but no statistically significant(P>0.05).5 The sensitivity to S-1 in TP high expression group(90%)of colorectal cancer cells in vitro was significantly higher than that in low expression group(9.38%)(P<0.05).The sensitivity to S-1 of OPRT high expression group(59.1%)of colorectal cancer cells in vitro was significantly higher than that in low OPRT expression group(5%) (P<0.05).6 The evaluated specificity of TP High expression was 90%, sensitivity 65%.The evaluated specificity of TP low expression was 84%, sensitivity 97%; The evaluated specificity of OPRT high expression was 59%, sensitivity of 97%. The evaluated specificity of low expression of OPRT could be 90%, sensitivity 68%; The evaluated specificity of dUTPase high expression was 60%, sensitivity was 75%. The evaluated specificity of the high expression of TP and the high expression of OPRT was 80%, sensitivity was 75%.Conclusion:1 Chemosensitivity assay could avoid using the resistant drugs and provide guidance to improve the clinical chemotherapy effect.MTT colorimetric assay is objective method with good repeatability.2 The expression of TP and OPRT were correlated with differentiation degree, lymph node metastasis, and Duck's stage. The expression of OPRT were correlated with lymph node metastasis and Duck's stage.3 TP and OPRT could serve as a prognostic factor and as a S-1 based chemotherapeutic efficiency index in patients with colorectal carcinoma. With high specificity and sensitivity of the evaluation.Before chemotherapy with S-1 in colorectal cancer.4 We applied MTT method in vitro drug sensitivity test and understood TP and OPRT by immunohistochemical method,which could improve the accuracy of the evaluation,could identify possible drug-resistant individuals, and would be possible to avoid ineffective chemotherapy.
Keywords/Search Tags:colorectal carcinoma, in vitro chemosensitivity assay, thymidine phosphorylase(TP), S-1(Tegafur,Gimeracil and Oteracil Potassium Capsules), orotate phosphoribosyl transferase(OPRT)
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