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In vivo antitumor effect of herpes simplex virus thymidine kinase gene therapy in rat hepatocellular carcinoma: feasibility of adenovirus-mediated intra-arterial gene delivery.
- Source :
-
Molecules and cells [Mol Cells] 2001 Apr 30; Vol. 11 (2), pp. 170-8. - Publication Year :
- 2001
-
Abstract
- Transfer of the herpes simplex virus-thymidine kinase gene, followed by the administration of ganciclovir (HSV-tk/GCV), has been a major approach for cancer gene therapy. We investigated the antitumor effect of the HSV-tk/GCV strategy with the rat orthotopic hepatocellular carcinoma (HCC) model and the tumor-selective gene delivery by an adenovirus-mediated gene transfer through the hepatic artery. The complete antitumor effect was demonstrated, after the treatment with GCV in rat HCC established by the implantation of HSV-tk transferred rat HCC cells. The in vivo bystander effect was also observed. The marked infiltration of CD4+ and CD8+ T lymphocytes, macrophages and NK cells were found in the tumor area. After the injection of adenovirus carrying the LacZ gene into the hepatic artery, the selective expression of transgene in the tumor cell was achieved. These findings indicate that the HSV-tk/GCV strategy, using an adenoviral vector, could be a promising avenue for the treatment of hepatocellular carcinoma.
- Subjects :
- Adenoviridae genetics
Adenoviridae metabolism
Animals
Antiviral Agents therapeutic use
Combined Modality Therapy
Ganciclovir therapeutic use
Genetic Vectors
Humans
Killer Cells, Natural cytology
Liver pathology
Liver physiopathology
Liver Neoplasms, Experimental pathology
Liver Neoplasms, Experimental physiopathology
Macrophages cytology
Male
Rats
Simplexvirus genetics
Thymidine Kinase metabolism
Tumor Cells, Cultured
Gene Transfer Techniques
Genetic Therapy methods
Liver Neoplasms, Experimental therapy
Simplexvirus enzymology
Thymidine Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1016-8478
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecules and cells
- Publication Type :
- Academic Journal
- Accession number :
- 11355697