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Gene Therapy On The Nude Mice Models Of Human Colocarcinoma With Wild Type P53 Gene And The System Of TK/GCV And CD/5-FC

Posted on:2006-06-24Degree:MasterType:Thesis
Country:ChinaCandidate:D WeiFull Text:PDF
GTID:2144360155966891Subject:Surgery
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Background Nowadays the incidence rate of human colocarcinoma becomes higher and higher. Surgery is always used as the main treatment of colocarcinoma, with some other ways, such as chemotherapy, radiotherapy and so on. In vitro test we have approved that WTp53 gene, TK/GCV and CD/5-Fc obviously inhibited the growth of SW480 cells, both TK/GCV and CD/5-Fc had bystander effect, and the combined genes had a greater antitumoral effect. So as to explore the probability of the gene therapy on human colocarcinoma with WTp53 gene and the System of TK/GCV and CD/5-Fc,we established the animal model of human colocarcinoma, treated them with genes above, and explored how they work. We have been expecting to supply the combined gene therapy on human colocarcinoma with new findings and credible experiment evidence.Objective To investigate the effect of the gene therapy on human colocarcinoma with WTp53 gene and the system of TK/GCV and CD/5-Fc, and to explore how the genes work.Methods The transplantation of cultivated cells was adopted. Nude mice were injected subcutaneously on the back with human colocarcinoma cells which belong to line SW480, so as to establish the animal model of human colocarcinoma. 48 nude mice were divided into 6 groups at random, which were comparison group,the group of WTp53,the group ofTK/GCV, the group of CD/5-Fc, the group of the system of TK/GCV and CD/5-Fc, the group of WTp53 and the System of TK/GCV and CD/5-Fc, and each group had 8 nude mice. WTp53 genes were mediated by Lipofectamine and TK> CD genes were mediated by the reverse transcription virus, and they all were injected directly into the tumor. Nude mice common status, tumor's bulk, tumor's weight, inhibition rate of tumor's growth, pathology, survival period, et al,were investigated.Results Each treated group especially the combined gene therapy group obviously inhibited the tumors' growth and prolonged the survival period significantly. The difference was significant between comparison and treated groups, and the combined gene therapy group worked more markedly. There was mutual effect between WTp53 gene and the system of TK/GCV and CD/5-Fc.Conclusions WTp53^ TK/GCV> CD/5-Fc obviously inhibited the growth of human colocarcinoma cell line SW480, and the combined genes had a greater antitumoral effect. They will have been probably used as the gene therapy of human colocarcinoma in the future.Significance We have succeded in establishing the animal model of human colocarcinoma in this experiment. In vivo test, the treatment of the gene therapy on human colocarcinoma with WTp53 gene and the system of TK/GCV and CD/5-Fc was significant. At the same time we have explored how they work, and supplied the combined gene therapy on human colocarcinoma with new findings and credible experiment evidence. Now we can forecast that WTp53^K/GCV>CD/5-Fc will have been probably used as the gene therapy of human colocarcinoma in the future, and the combined genes may have a greater antitumoral effect.
Keywords/Search Tags:Colorectal neoplasms, Mice, Gene, wild type p53, Thymidine kinase, Ganciclovir, Cytosine deaminase, 5-Fluorocytosine, Gene therapy
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