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An Clinical Study Of The Recombinant Human P53 Adenovirus Combined With Hepatic Arterial Chemoembolization On HCC And The Changes Of T Cell Subsets After The Treatment

Posted on:2016-07-29Degree:MasterType:Thesis
Country:ChinaCandidate:C Q ZhuFull Text:PDF
GTID:2284330461462204Subject:Surgery
Abstract/Summary:PDF Full Text Request
Hepatocellular carcinoma is one of the most common malignant tumorworldwide.China is one of the high-prevalence area.HCC is the second cancer-related deaths tumor behind the pulmonarycancer in China,which has been a serious threat to the health of the people,and Most of the patients have been in end-stage cancer patients in hospita.Surgical operation has been the main method for the treatment of HCC.Unfortunately,most patients have lost the chance of operation when see doctor,and HCC is not sensitive to radiation treatment and chemotherapy.Transcatheter arterial chemoembolization is the Main methodof the treatment for patients who have lost the chance of operation.Although its clinical effect is very obvious,its also has several disadvantages,Such as the necrosis of the tumor and the incomplete eliminating,In addition residual child of the tumor may exist,and the immune function could be damaged after the operation.TACE is used routinely in the middle-late stage of hepatocellular carcinoma,However,for the effects on the body’s immunefunction,the results are inconsistent.The T-cell subgroup of hepatocellular carcinoma patients were detectded both pre-TACE and post-TACE.Compared the testing results of the T-cell subgroup of combination with p53 both pre-TACE and post-TACE,we have obtained a preliminary understanding of the effects.It may provide a certain basis for the comprehensive treatment of hepatocellular carcinoma.Restructuring of p53 adenovirus injection(Gendicine),genetically engineered activity virus granules has An infection ability(r Ad-p53).It consists of the defective copied human adenovirus type 5 carrier and normal p53 tumor suppressor genes.It is a product of cancer gene therapy.It has been approved by the China’s state food and drug administration(approval number:S20040004) and is the first listed tumor gene therapy in the world.It has been reported that it is safe and effective to use the r Ad-p53 products within the tumor injection,intraperitoneal perfusion,bladder perfusion, endobronchial drip,hepatic artery injection and peripheral vein dosing to treat a variety of malignant both in part of the body or the whole body.The tumor tissue or blood sample of petients with a trentment showed that recombinant adenovirus p53 gene particles can effectively infect tumor cells,And can transcript and express,Besides it can directly or indirectly regulate the expression of related genes inhibiting tumor cell growth and induce cell apoptosis.Because of its clinical effect is remarkable, the gene therapy gradually become an important auxiliary method of tumor treatment.Objective: To understand the recombinant adenovirus p53 gene combination with the transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma in the clinical curative effect,life quality,imaging changes and T cell subgroup changes before and after treatment.Method:1 The 40 patients with terminal-stage of HCC were collected from March 2013 to December 2014 in liver and gallbladder surgery,workers hospital,tangshan,hebei.2 The 40 patients with moderate or terminal HCC were divided into the experimental group and control group according to whether the combined with the recombinant adenovirus p53 gene,and all treated with TACE,20 patients with advanced HCC treated only with TACE served as control group. Another 20 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as experimental group.3 All the patients were treated with TACE under DSA,the experimental group patients were given the recombinant p53 adenovirus injection 2-3(2x1012vp-3x1012vp).All the patients were taken peripheral blood to using flow cytometry to detect T cell subgroup at 1 day of the preoperative, postoperative 1 week,2 weeks after operation,postoperative 4 weeks.4 After the treatment,all of the patients,all of them were followed up.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,immune function,leukocyte count,imaging changes,AFP,Karnofsky and RECIST criteria.Result: Based on RECIST criteria,the experimental Group has CR 0 cases,13 cases of PR,SD in 5 cases,PD in 2 cases,the control group has CR 0 cases,9 cases of PR,SD 7 cases,PD 4 cases.The effective rate of experimental group and control group were 65.0%,45.0% respectively.The experimental group of T cell subgroup level quality significantly improved than the control group after treatment(P<0.05). The tumor body was reduced more significantly(P<0.05) and Karnofsky score was higher(P<0.05) in experimental group.The AFP was declined more significantly(P<0.05) in experimental group.There was no was no significant difference for the other adverse effects of the postoperativebetween two groups(P>0.05). Compared with control group,the number of tumor progress after treatment in the experimental group was less(P<0.05).Conclusion: The treatment of recombinant adenovirus-p53 injection in combination with TACE for patients with advanced hepatocellular carcinoma can strenghthen the anti-cancer effect and improve the life quality of patients.The r Ad-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC,and the body of T cell subgroup level obviously higher than the TACE without r Ad-p53.T cell levels were significantly higher than those preoperative.Suggesting an dramatical improvement after the operation.
Keywords/Search Tags:Hepatocellular carcinoma, transcatheter hepaticarterial chemoembolization, recombinant adenovirus-p53, gene therapy, T cell subgroup
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