The Empirical Study Of Gene Therapy To Hepatoma With Ad-p53 By Intervention Targeting

Objective:Evaluating various methods to make rabbit model of VX₂ tumor and studying the imaging manifestation. To investigate the effect of interventional treatments on the expression of p53 gene matrix metalloprotein-2 (MMP-2) and vascular endothelial growth factor (VEGF).Materials and methods:1. 60 New Zealand rabbits were implanted VX2 tumor by three methods: laparotomic bury, laparotomic puncture and percutaneous puncture, 20 rabbits per group, 10 injected with carcinoma masses and 10 with carcinoma fluids in every group. CT, MRI and liver angiography were procedured after two weeks of inoculation.2. VX2 carcinoma cells were surgically implanted into the left liver lober of 48 New Zealand white rabbits, which were divided into 4 groups at random, with 12 rabbits for each group .Before the treatments, the diameters of the tumors were acquired by MRI. Physiological saline (compared group), Lipiodol(group 1) , Ad-p53(group 2) and Lipiodol + Ad-p53 (group 3)were infused in different groups via common hepatic artery . After two weeks the rabbits were killed and the livers were resected, some tumor tissues were sampled make paraffin section (H E staining) and observe the necrosis of tumor tissue with microscope. P53 MMP-2 and VEGF of tumor were examined by immunohistochemistry .3. Statistical analysis: The data was analyzed by using the SPSS12.0. A P value of less than 0.05 was considered to indicate statistical difference.Results:1. Implantation rate was significantly high in two laparotomic route compared with percutaneous methods. The VX₂ liver tumors demonstrated as hypodensity on plain CT scan and enhanced on early artery phase and Hypodensity on portal phase images. On MR scans the VX₂ liver tumors were seen as hypointensity on T1WI and slightly hyperintensity on T2WI. Hepatic angiography showed the tumors were hypervascular and hepatic artery is the main blood feeding vessels. Necrosis and bleeding were often found in the area of VX₂ liver tumors after two weeks of implantation.2. The positive rates of p53, MMP-2 and VEGF were slightly higher in single lipiodol embolization group, but has no significant vs physiological saline group (P>0.05). The positive rates of p53, MMP-2 and VEGF in groups 2 and 3 were significantly lower than those of compared group (P<0.05). In the rabbits with metastasis, the positive rates of p53, MMP-2 and VEGF were markedly higher than those of no-metastasis rabbits (P<0.05).Conclusion:1. Making VX2 liver tumor model by laparotomic route were simple and short circled. The rabbit model with VX₂ liver tumor is similar to hepatic primary carcinoma of human beings.2. The growth , metastasis and vasiformation of rabbit liver tumors could be partially inhibited by Ad-p53 .The high positive rates of p53 ,MMP-2 and VEGF indicated high metastasis , proliferation potentiality and vasiformation potentiality,,...