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The Study On The Expression Of CD73、dll4 In RCC And The Research Of Recombinant PEAs-pVAX1-DLL4 In The Subcutaneously Transplanted Tumor In Rat

Posted on:2016-02-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y YuFull Text:PDF
GTID:1224330503450061Subject:Surgery
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Renal cell carcinoma(takes cell carcinoma, RCC) is common malignant tumor, originated in the renal parenchyma and urinary tubular epithelium in the elderly. RCC lack of rehabilitation treatment except for surgical treatment. In turn, the study evrify the surface molecules of RCC to initiate a new treatment. All statistical data analysised by SPSS19.0 software. The correlation with clinical data analysised with rank and multivariate linear regression.The relationship between the clinical pathological parameters using the Mann- Whitney U and Kruskal Wallis H test. In this study, we selected the specimens of 159 cases of renal cancer(clear cell carcinoma and cell carcinoma) and 30 cases of normal kidney tissues adjacent to carcinoma in kidney cancer patients from 2004.5 to 2012.5 in the Second hospital of Lanzhou university and tested the expression proteins of CD73, DLL4 and P- gp in renal clear cell carcinoma and urothelial carcinoma determination by immunohistochemical technique(two-step method) and correlated the surface molecular positive expression with the clinical stage and prognosis. Using SPSS19.0 software for statistical analysis.Counting data was described by the number and percentage under Fisher’s exact probability method. In comparison with the normal tissue, CD73 75 cases in 159 cases of renal cell carcinoma(p = 0.000),there is no statistical significance(p = 0.074)on CD73 expression of vascular wall. And strong expression of P- gp are 42 cases of 85 cases of kidney tissue within the blood vessels and there is statistical significance, unlike the expression of P- gp is no obvious difference between normal renal tissues and renal cancer cells. 58.43%DLL4 expression(52/89 cases) comparing 5.89% normal tissue adjacent to carcinoma(1/17cases) was statistically significant(p = 0.000), the expression of DLL4 on the blood vessels was no statistical difference between them. CD73 expression level in kidney cells and tumor type(p = 0.000), tumor TNM staging(p = 0.002)and grading(p = 0.002)exist significant correlation.P- gp is only related to renal cell carcinoma TNM staging(p = 0.015)and grading(p = 0.026). DLL4 expression level in kidney cells and gender(p = 0.975),tumor type(p = 0.197), and grading(p = 0.786)(p = 0.002)exist no significant correlation except tumor TNM staging(p = 0.009).COX multivariate linear regression analysis, only the expression of CD73(p = 0.037) and tumor grade(p = 0.035) associated with patient survival in RCC. The strong expression of P- gp(P = 0.065) and DLL4(P = 0.536) has no danger to do with the disease.In the kidney cancer cells, the median survival time of the CD73 patients with strong expression(62.06 + /- 5.35 months)was significantly shorter than the lack expression of CD73(103.72 + /- 103.72 months). So it is concluded that CD73 expression level is closely related to renal cell carcinoma, likely as the diagnosis and prognosis of renal cell carcinoma related factors, also can be used for the treatment of renal cell targets.Development of molecular produces a wonderful effect on targeted therapy vaccine for clinical including tumor. Kunming mice used H22 cell lines established in subcutaneous transplantation tumor were injected recombinant plasmids PEAs – pVAX1- DLL4 in vivo and vitro,and exploried the level of molecular biology and effect. DLL4 plasmid group of kunming mice survival time is 33.14±6.06 days, and survival days of 27.67±6.02 days, the empty plasmid group survival days for 27.67±9.54 days. The weight of Dll4 plasmid group tumor was 4.12±2.52 g compared the weight of empty plasmid group tumor(5.90±3.97g)and the control group(6.26±3.01g)has no statistically significant. Tumors volume of control group(17.11±9.30 cm3)has statistical significance(P=0.035) comparing with plasmid group(5.08±2.75cm3).Plasmid tumor growth inhibition rate was 70.31%,wheareas tumor inhibition rate was 34.19%.CD4 positive expression increased significantly on plasmid group(32.41±4.19 pg/ml)compared with the control group15.67±7.02 pg/ml(P =0.001), the empty plasmid group 17.99±6.71 pg/ml(P =0.005). The expression of IL2, IL4, r- IFN is highest in plasmid groups, significancly. So, DLL4 CDNA may transfect in vitro and in vivo and slowed tumor growth through activition of helper T cell, but little influence on other cell biology. DLL4 CDNA a promising genes may relapse prevention and treatment on tumor.
Keywords/Search Tags:CD73, P-Glycoprotein, Delta-like ligand 4(DLL4), Vaccine, Recombinant Plasmid PEAs-pVAX1-DLL4
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