Gene Therapy For Hepatoma Cells Using A Retrovirus Vector Carrying Cytosine Deaminase Gene Under The Control Of Human Alpha-Fetoprotein Gene Regulatory Sequences

Hepatocellular carcinoma (HCC) is one of the most common human malignancies. It causes an estimated 1,250,000 deaths per year worldwide. The incidence of this cancer is high in Southeast Asia, especially in China, where it is associated with hepatitis B and C infection and exposure to aflatoxin. As HCC does not respond well to current treatment, gene therapy sounds attractive in the management of this disease.Selective expression of chemosensitivity gene (suicide gene) products in tumor cells is one of the goals in gene therapy of cancer. In order to achieve selective killing of retrovirally transduced HCC cells, we developed a strategy for the treatment of HCC by linking the E. coli. cytosine deaminase (CD) gene to HCC-associated transcriptional regulatory elementsFirstly, using gene recombinant technique, we constructed six eukaryotic expression plasmids of luciferase reporter gene which had different AFP transcriptional regulatory (?)equences. They were pGL-0.2p(only 0.2kb AFP promoter), pGL -0.4p (0.2kb AFP promoter and 0.2kb AFP silencer), pGL-1.8p (0.2kb AFP promoter and 1.6kb region containing proximal silencer and distal silencer), pGL-2.2p (0.2kb AFP promoter...