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A Fundamental Research Of Tumor Immune Gene Therapy's Curative Effect To Metastasis Malignant Tumor

Posted on:2004-09-22Degree:MasterType:Thesis
Country:ChinaCandidate:X D ZhangFull Text:PDF
GTID:2144360095457894Subject:Oncology
Abstract/Summary:PDF Full Text Request
E1B gene-deleted adenovirus injection is put into clinical apply from several years ago as a gene therapy method. It can selectively copy in tumor cells and indues rumor cells'death in different mechanisms. However, the special character for the difficult of malignant tumor curation is its metastasis consequently. It is very important to research wether rumor gene therapy working in coordinate with HSP (heat shock protein) can improve local tumor special antigen offering and induce body's tumor immunological kill mechanism to produce positive kill effect for small metastasis tumors.Objective: E1B gene-deleted adenovirus antigen can induce the expression of MHCI in infected tumor cells'surface and make body produce cytoxic reaction for virus and distroy them therefore.which is one of its kill mechanisms.Heat therapy can produce HSP through heat stress ?HSP act important effect in rumor immunology as molecular partner. After antigen peptides in cells being broken down into short peptides by enzyme and combined with HSP, they are transported to endoplasmic recticulum to connect with MHCI and come into being HSP antigen complex (HAC) expressing in the surface of tumor cells. Then,T lymphocytes distinguish it and attack tumor cells , HAC in tumor tissue maybe combine different tumor antigen peptides and can active different CTL colons to kill all rumor cells in one tumor after immuning body. In this test, heat therapy can produce HSP through heat stress and improve effects for tumor special antigen offering and induce tumor special immunology to kill metastasis tumor cells.Method: there are 40 mice that are randomized into 4 groups evenly .Half male mice and half female mice are in every group.The 4 groups are divided as followed: E1B gene-deleted adenovirus group (E1B gene-deleted adenovirus injection),heat therapy group(heat therapy+sodium chloride injection), E1B gene-deleted adenovirus +heat therapy group (E1B gene-deleted adenovirus injection+heat therapy),control group(sodium chloride injection).The test periode is 21 days.2X106 tumor cells are injected in two flanks.Waiting tumors grow up to about 5mm, I start the test.Heat therapy group and E1B gene-deleted adenovirus+heat therapy group were heated for 15 minutes (10W) by microwave heat therapy machine. After heated,two mice were taken out from every group for immunological histochemistry to observe HSP.Then E1B gene-deleted adenovirus group and E1B gene-deleted adenovirus+heat therapy group were injected E1B gene-deleted adenovirus injection (1X109granules/one) in right tumor,heat group and control group were injected same volume sodium chloride injection in right tumor continuing for 3 days,one time every day. After administrating,the largest left tumor diameter and its vertical diameter were measured one time every three days for 6 times for counting tumor volume and tumor suppressive rate.At 21 day ,0.5 ml blood was taken from every mouse for observing cell immunology (flow cytometer , FCM) and kill the mice to take out left tumor for weighing tumor weight after that.At the same time,the right lymph nodes were taken.Right lymph nodes was dyed to observe lymph metastasis.Result: HSP immunological histochemistry's result is shown in picture 1.The HSP production in heat group and unheat group is significantly different. Left tumor volume measures are as figure 1. E1B gene-deleted adenovirus group, heat therapy group and E1B gene-deleted adenovirus+heat therapy group P quantity are 0.072,0.093,0.01 compare to control group, E1B gene-deleted adenovirus+heat therapy group has more significant difference (P<0. 05) . Left tumor weight measures'results are as figure2. E1B gene-deleted adenovirus group, heat therapy group and E1B gene-deleted adenovirus+heat therapy group's P quantity are 0.026,0.035,0.005,which all have significant difference (P<0. 01). CD4,CD8's percentage and CD4/CD8 rate's result are as figure 4.From the figure,we can see CD8(CTL)of E1B gene-deleted adenovirus group, heat therapy group and E1B gene-deleted adenovirus+heat therapy g...
Keywords/Search Tags:E1B gene-deleted adenovirus, heat therapy, cell immune, malignant tumor, metastasis
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