Quillien V, Heresbach Le Berre N, Dufour T, Denais A, Guegan Y, Ferry N, Bloin V
Laboratoire de transfert de gènes Inserm U. 49, Centre Eugène-Marquis, Rennes, France.
Bull Cancer. 1997 Nov;84(11):1047-52.
Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal model of brain tumor which was obtained by injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV beta gal resulted in the expression of the marker gene in 61% of the animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in 50% of the rats treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6, the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.
我们的目的是在脑肿瘤动物模型中测试腺病毒介导的基因治疗效果，该模型通过将9L胶质肉瘤细胞注射到大鼠脑尾状核获得。肿瘤细胞植入7天后，将携带大肠杆菌β-半乳糖苷酶基因（ADVβ-gal）或单纯疱疹病毒胸苷激酶基因（ADVtk）的腺病毒载体立体定向注射到肿瘤中。注射ADVβ-gal导致61%的动物中标记基因表达。3天后，在注射ADVtk后，腹腔注射更昔洛韦（GCV）10天。对照组用生理盐水代替GCV治疗。与对照动物相比，我们观察到在接受ADVtk和GCV治疗的大鼠中，50%的肿瘤出现显著消退。在6例中的4例中，治疗后肿瘤完全消失。这些结果证明了腺病毒介导的HSVtk基因转移继以GCV给药治疗胶质母细胞瘤的潜在疗效。
