Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.
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.
Gérolami
R
R
INSERM U 370, Faculté Necker, Paris, France.
Cardoso
J
J
Bralet
M P
MP
Cuenod
C A
CA
Clément
O
O
Tran
P L
PL
Bréchot
C
C
D000256:Adenoviridae; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000628:therapy*; D004052:Diethylnitrosamine; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed; D001616:beta-Galactosidase / Q000235:genetics
D004052:Diethylnitrosamine; D001616:beta-Galactosidase