Experimental Studies Of Endostatin Infusion Through Hepatic Arteries With Transcatheter Arterial Chemoembolization On The Treatment Of Rat's Transplanted Hepatoma

Part-1:Establishment of Walker-256 transplanted hepatoma model in rat and investigation on tumor angiogenesisObjective:Through the establishment of rat Walker-256 hepatoma model to analyze its features of imageology and pathology, so as to evaluate the feasibility of the application of the animal model in anti-angiogenesis for hepatoma treatment;as well as investigate the formation state of its tumor angiogenesis.Methods:Walker-256 hepatoma models were established by transplantation on 17 Wistar rats, MRI,DSA and histopathologic examinations were carried out on the 8th day,16th day post-transplantation respectively. The capacity of the tumor, imageologic features and histopathological changes were observed.Results:17 rats were confirmed successful transplantation by MRI,the capacity of the tumor was 88.40±7.62mm3 on 8th day, 986.80±114.46mm3 on 16th day,the volume growth was 8-12 folds;on 8th day following transplantation,the tumor tissue was gray in color with fish homogen state without interior necrosis, the tumor cells were nest-distributed by HE staining,large dense staining of nucleus with manifest heteromorphism,tumor microvessel count increased by immunohistochemistry with buffy yellow staining, VEGF high expressed in the tumor cells with buffy yellow granule shape. On 16th day,the tumor tissue was white fish shape with interior necrosis, tumor periphery cells were close-up by HE staining,different degree of necrosis zones were in the centre, the expression levels of MVD and VEGF were all higher than that of the 8th day by immunohistochemistry;Pearson correlation analysis of the expression levels of MVD and VEGF in liver tumor demonstrated:the averge optical of MVD had linear positive correlation with that of VEGF. Conclusions:Walker-256 hepatoma model of rat is applicable for the interventional empirical study of hepatoma, tumor vascularization has close relationship with the expressions of MVD and VEGF, MVD value of tumor tissue and the expression level of VEGF extensively reflect the state of tumor vascularization. Part-II:Endostatin infusion through hepatic arteries with transcatheter arterial chemoembolization on the treatment of rat's transplanted hepatoma.Objective:By endostatin infusion through hepatic arteries with transcatheter arterial chemoembolization on the treatment of rat's transplanted hepatoma,to investigate its therapeutic efficacy and application value. Methods:30 cancer-bearing modeling rats were divided into three groups, with 10 rats in each group.Gastroduodenal artery retrograde catheterization was performed following MRI on 8th day after tumor transplantation. The treatment plan was as the following:A group, 0.2-0.3ml normal saline was slowly infused through hepatic artery;B group,mitomycin+supra-liquation iodipin were slowly infused through hepatic artery;C group, mitomycin+iodipin +endostatin were slowly infused through hepatic artery. MRI was re-performed on the 16th day of tumor transplantation. The growth rate of tumor was calculated by the volume changes of tumor circle interventional therapy;the expressions ofⅧand VEGF in tumor tissue were detected by immunohistochemistry, as well as photo densitometry was performed on VEGF positive tumor cells and microvessel density. Results:A group:the volume before and after operation and the growth rate of tumor treatment were:88.40±7.62,986.80±114.46,1024.50±168.15;B group:85.60±6.48,567.80±87.80,571.60±143.87 ; C group:83.60±6.60,370.50±53.68,345.16±70.23,respectively.Statistics demonstrated both of B,C groups had inhibitive effect on the growth of tumor, C group had more stronger tumor growth inhibitive function vs.that of B,C groups. The average optical values of MVD and VEGF in A,B,C groups were not completely same,in two group comparason, there was significant difference in C group and A,B groups(p<0.01), the average optical values of MVD and VEGF in A,B groups had no signficant difference(p>0.05).Conclusions:Endostatin infusion through hepatic arteries with transcatheter arterial chemoembolization can suppress the growth of transplanted hepatoma manifestly and it has predominant inhibitive function on the microvessel population of tumor tissue and the expression of VEGF.