Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery
Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery
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DOI：
10.1038/sj.gt.3300664
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发表时间：
1998-07-01
期刊：
影响因子：
5.1
通讯作者：
Brechot, C
中科院分区：
文献类型：
--
作者：
Gerolami, R;Cardoso, J;Brechot, C
腺病毒介导的实验性肝癌基因治疗因体内转导效率低而受到阻碍。我们评估了重组腺病毒 AdCMVlacZ 不同给药途径在二乙基亚硝胺诱导的大鼠肝癌中的基因表达程度。我们首先使用计算机断层扫描方法描述了二乙基亚硝胺诱导的肝癌的血管化。然后通过三种给药途径评估基因转移的功效：门静脉内、通过肝动脉选择性注射和直接注射到肿瘤中。二乙基亚硝胺诱发的肝癌主要有动脉血供，占肝脏总血供的 67%。与门静脉注射相比，动脉注射改善了基因向肿瘤的转移，而向非肿瘤区域的基因转移则减少。此外，这种注射途径可以有效转导发育不良结节。二乙基亚硝胺诱导的大鼠肝癌因其血管化而成为研究人类肝癌的相关模型。动脉输注提高了转导的肿瘤细胞与非肿瘤细胞的比率，并允许将基因转移靶向发育不良结节。这将有助于肝癌基因治疗的设计。
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.