Vincent A J, Vogels R, Someren G V, Esandi M C, Noteboom J L, Avezaat C J, Vecht C, Bekkum D W, Valerio D, Bout A, Hoogerbrugge P M
Department of Neurosurgery, University Hospital Rotterdam, Netherlands.
Hum Gene Ther. 1996 Jan 20;7(2):197-205. doi: 10.1089/hum.1996.7.2-197.
Transfer of a herpes simplex virus-derived thymidine kinase (HSV-tk) gene into brain tumor cells and subsequent ganciclovir (GCV) treatment has been shown by others to be an effective treatment in rats with intracerebrally inoculated 9L gliosarcomas. Mechanism of action and reproducibility are, however, still a matter of debate. We have used the same model to test the therapeutic effects of both retrovirus- and adenovirus-mediated transfer of the HSV-tk gene followed by GCV treatment. Survival time of rats with intracerebral 9L tumors was significantly prolonged after a single administration of adenovirus carrying a HSV-tk gene as compared to controls. Retrovirus-mediated gene transfer also resulted in significantly prolonged survival time when recombinant retrovirus-producing cells were transplanted. Direct injection of the recombinant retrovirus, HSV-tk-expressing cells, virus-producing cells without GCV administration and recombinant retrovirus-lacZ or interleukin-2 (IL-2)-producing cells did not result in tumor cell kill. In the present study, no significant difference in survival of 9L brain tumor carrying rats was found after treatment with adenovirus as compared to retrovirus-mediated HSV-tk-mediated gene transfer and subsequent GCV treatment.
其他人已证明，将单纯疱疹病毒来源的胸苷激酶（HSV-tk）基因导入脑肿瘤细胞并随后进行更昔洛韦（GCV）治疗，对于脑内接种9L胶质肉瘤的大鼠是一种有效的治疗方法。然而，其作用机制和可重复性仍是一个有争议的问题。我们使用相同的模型来测试逆转录病毒和腺病毒介导的HSV-tk基因转移并随后进行GCV治疗的疗效。与对照组相比，单次给予携带HSV-tk基因的腺病毒后，脑内有9L肿瘤的大鼠存活时间显著延长。当移植产生重组逆转录病毒的细胞时，逆转录病毒介导的基因转移也导致存活时间显著延长。直接注射重组逆转录病毒、表达HSV-tk的细胞、不给予GCV的病毒产生细胞以及产生重组逆转录病毒-乳糖酶或白细胞介素-2（IL-2）的细胞均未导致肿瘤细胞死亡。在本研究中，与逆转录病毒介导的HSV-tk介导的基因转移并随后进行GCV治疗相比，用腺病毒治疗后，携带9L脑肿瘤的大鼠的存活率没有显著差异。
