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The Mechanism Research Of ??T Inhibiting The Growth Of Pancreatic Cancer Cell

Posted on:2018-10-20Degree:MasterType:Thesis
Country:ChinaCandidate:X X ZhuFull Text:PDF
GTID:2334330515454553Subject:Surgery
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Objective On the basement of our previous researchs which showed that ??T cell could inhibit pancreatic carcinoma cellsobviously in vitro.This research aimed to investigate the effects of Unique long 16-binding proteins(ULBP)in ??T cell inhibiting the growth of pancreatic carcinoma of mice model.Besides,we also studied the expression of ULBP in PDA and its diagnostic importance for PDA.Methods Gamma delta T cells were separated from peripheral blood of healthy volunteers by antibodies adsorption separation.Pancreatic cancer cell lines PANC-1 was injected on the back of BALB/c nude mice to establish animal model of pancreatic cancer by subcutaneous injection.We divided mice into blank group,the group treated with gemcitabine and gamma delta T cells randomly,each group of eight.Gamma delta T was infused into the nude mouse by tail vein,after amplification in vitro.Measuring weight and tumor twice a week.After,the mice were euthanized with cervical dislocation and tumor tissue were taken out to calculate the relative tumor size and the tumor inhibition rate.The experiment of WB and q-PCR were taken to detect ULBPs expression in pancreatic cancer in three groups respectively.IHC was taken to detect the expression of ULBPs in tumor tissues and adjacent tissues to carcinoma of 30 patients with pancreatic cancer.The content of ULBPs and CA199 in peripheral blood and its diagnosis value for PDA were detected by ELISA and ROC curve.Results Pancreatic cancer growth was inhibited in the group of gamma delta T cells(P = 0.003),whose inhibition rate had no difference with the group of gemcitabine.IHC experiment of human pancreatic cancer tissue and WB experiments of nude mice tumor tissue indicate that ULBP are expressed in pancreatic cancer tissue highly.In addition,the WB experiments show that expression level of ULBP – 1 and ULBP-3 will decline after the treatment of gamma delta T(P = 0.025,P = 0.025).However,q-PCR showed that ULBP1 gene expression will rise after treatment with gamma delta T cells.s-ULBP2 in the peripheral blood of patients with pancreatic cancer in content is higher than that of healthy people.The diagnosis for PDA are better when combing s-ULBP2 and CA199 than CA199 alone[AUC=0.88(95%CI:0.807~0.943);AUC=0.84(95%CI:0.761~0.917)].Conclusion ??T cell can significantly inhibit the growth of pancreatic carcinoma in vivo,which was correlated with the abnormal expressions of ULBP.The diagnosis value of combination of CA199 and s-ULBP2 is higher than CA199 alone.
Keywords/Search Tags:??T cell, PDA, NKG2D, ULBP, Immunotherapy
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