GENE-THERAPY FOR BRAIN-TUMORS - REGRESSION OF EXPERIMENTAL GLIOMAS BY ADENOVIRUS-MEDIATED GENE-TRANSFER IN-VIVO
GENE-THERAPY FOR BRAIN-TUMORS - REGRESSION OF EXPERIMENTAL GLIOMAS BY ADENOVIRUS-MEDIATED GENE-TRANSFER IN-VIVO
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DOI：
10.1073/pnas.91.8.3054
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
WOO, SLC
中科院分区：
文献类型：
--
作者：
CHEN, SH;SHINE, HD;WOO, SLC
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胶质瘤细胞后给予更昔洛韦（GCV）对裸鼠脑肿瘤的治疗效果。用携带HSV-tk基因的复制缺陷型重组腺病毒（ADV/RSV-tk）在体外有效地转导C6胶质瘤细胞，使其对GCV敏感，并呈剂量依赖性。通过在裸鼠脑内立体定位注射1 × 10（4）个C6细胞产生肿瘤。肿瘤生长8天后，将3 × 108 ADV/RSV-tk病毒颗粒注射到肿瘤中，随后用GCV处理小鼠6天。在肿瘤植入后20天比较未处理和处理的动物中的肿瘤大小。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>500倍。这些结果表明，重组腺病毒载体可以作为一个有效的基因载体的治疗胶质瘤的体内基因治疗。
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.