Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery
| Autor: | Phuong Lan Tran, René Gerolami, Clément O, Cuenod Ca, Jorge Cardoso, Marie-Pierre Bralet, Christian Bréchot |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Pathology medicine.medical_specialty Carcinoma Hepatocellular Genetic enhancement Genetic Vectors Gene Expression medicine.disease_cause Adenoviridae Transduction (genetics) Hepatic Artery Liver Neoplasms Experimental In vivo Gene expression Genetics medicine Animals Diethylnitrosamine Rats Wistar Molecular Biology business.industry Genetic transfer Gene Transfer Techniques beta-Galactosidase medicine.disease digestive system diseases Rats medicine.anatomical_structure Injections Intra-Arterial Hepatocellular carcinoma Molecular Medicine Tomography X-Ray Computed business Artery |
| Zdroj: | Gene Therapy. 5:896-904 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vascularization of diethylnitrosamine-induced hepatocarcinomas using a computerized tomography scanner approach. The efficacy of gene transfer was then evaluated by three routes of administration: intraportal, selective injection through the hepatic artery and direct injection into the tumor. Diethylnitrosamine-induced hepatocarcinomas had predominantly an arterial blood supply, 67% of the total liver blood supply. Compared with intraportal administration, arterial injection improved gene transfer into tumors whereas that to the non-tumor areas was diminished. In addition, this route of injection allowed the efficient transduction of dysplastic nodules. Diethylnitrosamine-induced hepatocarcinoma in rats is a relevant model for the study of human hepatocarcinoma due to its vascularization. Arterial infusion improved the ratio of transduced tumorous to nontumorous cells and allowed targeting of gene transfer to dysplastic nodules. This will be useful in the design of gene therapy for hepatocarcinoma. |
| Databáze: | OpenAIRE |
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