Chen S H, Shine H D, Goodman J C, Grossman R G, Woo S L
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3054-7. doi: 10.1073/pnas.91.8.3054.
The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6 glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6 glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 10(4) C6 cells in nude mice. After 8 days of tumor growth, 3 x 10(8) ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by > 500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.
在裸鼠脑内生成的肿瘤中，研究了腺病毒介导的单纯疱疹病毒胸苷激酶（HSV-tk）基因转导大鼠C6胶质瘤细胞并随后给予更昔洛韦（GCV）后的治疗效果。携带HSV-tk基因的复制缺陷型重组腺病毒（ADV/RSV-tk）在体外能有效地转导C6胶质瘤细胞，使其对GCV呈剂量依赖性敏感。通过在裸鼠脑内立体定向注射1×10⁴个C6细胞生成肿瘤。肿瘤生长8天后，向肿瘤内注射3×10⁸个ADV/RSV-tk病毒颗粒，随后对小鼠给予GCV治疗6天。在肿瘤植入20天后比较未治疗和治疗动物的肿瘤大小。治疗动物的肿瘤平均横截面积比对照动物小23倍，肿瘤体积减少了>500倍。这些结果表明，重组腺病毒载体可作为一种有效的基因传递载体，通过体内基因治疗用于治疗胶质瘤。
