Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma

2010 
Objective To investigate the therapeutic effect and biological changes of hepatic arterial perfusion of p53 gene via port catheter system (PCS) on advanced hepatocellular carcinoma.Methods A total of 48 cases of advanced hepatocellular carcinoma were divided into the experimental group(30)and the control group(18).Transiliaca external artery PCS implantation was performed in all cases.p53 gene was perffused into target artery confirmed by angiography.In the experimental group,1012 VP of p53 gene and 20 mg OPT were employed everyweek as a course for 21 days.In the control group,only 20 mg OPT was used.KPS,AFP and the survival period,RECIST ( response evaluation criteria in solid ) tumor were analyzed.Flow cytometry (FCM) and micronucleus (MN) assay in vivo were used to detect p53 gene mutation and spontaneous micronucleus formation in peripheral blood of the experimental group.Results The experimental group were performed 1 to 8 courses.There was a significant difference with AFP level and KPS in the experimental group( P 0.05 ) in the control group.After one month,survival rate of the the experimental group and the control group was 96.6% and 94.4%,there was a significant difference between the two groups in objective tumor relieve (P<0.05).After three months,survival rate of the the experimental group and the control group was 83.3% and 55.6%,there was a significant difference between the two groups in objective tumor relieve (P<0.05).After six months,survival rate of the the experimental group and the control group was 50.0% and 11.1%,there was a significant difference between the two groups in objective tumor relieve ( P<0.05 ).After nine months,survival rate of the the experimental group and the control group was 23.3% and 0%,there was a significant difference between the two groups in objective tumor relieve (P< 0.05 ).After twelve months,survival rate of the the experimental group and the control group was 6.67% and 0%,there was a significant difference between the two groups in objective tumor relieve ( P<0.05 ).The depression of p53 expression was observed in the HCC patients who were employed four times of intervention operations.The difference of p53 expression between before and after interventional rAd-p53 therapy were statistically significant (P <0.01 ).The frequency of MN depressed by the rAd-p53 was seen in the patients,and the differences of the frequency of MN between before and after interventional rAd-p53 therapy were statistically significant ( P <0.05).Conclusion p53 gene sequential infusion via hepatic artery is effective for advanced hepatocellular carcinoma.The biological study will play a important role in selecting the therapeutic dose and judging therapeutic efficacy by means of guiding and monitoring. Key words: Radiology,interventional; Liver neoplasms; Genes,p53
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