Treatment of rat experimental brain tumors by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir
Treatment of rat experimental brain tumors by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir
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单纯疱疹病毒胸苷激酶基因转导的同种异体肿瘤细胞与更昔洛韦治疗大鼠实验性脑肿瘤
作者：
H. Namba;M. Tagawa;T. Miyagawa;Y. Iwadate;S. Sakiyama
单纯疱疹病毒胸苷激酶（HSVtk）基因的转移，随后给予更昔洛韦（GCV），产生“旁观者效应”，其中HSVtk阴性野生型细胞被GCV杀死，表达HSVtk的细胞也是如此。我们以前的研究表明，颅内9 L胶质瘤可以有效地治疗，由于这种旁观者效应，通过注射与HSVtk基因转导的9 L胶质瘤细胞在附近的预植入野生型9 L胶质瘤，然后给予GCV。对于旁观者效应介导的细胞杀伤的可能临床应用，我们测试了HSVtk基因转导的同种异体C6胶质瘤细胞（C6 tk），而不是用HSVtk基因转导的同基因9 L胶质瘤细胞。Fisher大鼠颅内植入野生型9 L神经胶质瘤细胞，随后在相同的脑坐标处注射C6 tk细胞，然后用GCV或盐水处理。当用GCV处理大鼠时，通过连续磁共振成像观察到肿瘤生长的显著延迟，尽管这种生长延迟不如用转导有HSVtk基因的9 L胶质瘤细胞观察到的显著;因此，存活时间延长（P <0.01）。接受C6 tk细胞的肿瘤在用GCV治疗后几乎不含HSVtk阳性细胞。同种异体肿瘤细胞的排斥，虽然可能在脑中不完全，也可以有助于这种治疗策略的安全性。
Transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, followed by administration of ganciclovir (GCV), generates the “bystander effect,” in which HSVtk-negative wild-type cells are killed by GCV, as are HSVtk-expressing cells. Our previous study demonstrated that intracranial 9L gliomas could be efficiently treated due to this bystander effect by injecting the 9L glioma cells transduced with the HSVtk gene in the vicinity of the preimplanted wild-type 9L glioma and then administering GCV. For a possible clinical application of the bystander effect-mediated cell killing, we tested HSVtk gene-transduced allogeneic C6 glioma cells (C6tk) instead of syngeneic 9L glioma cells transduced with the HSVtk gene. Fisher rats were implanted intracranially with wild-type 9L glioma cells, subsequently injected with C6tk cells at the same brain coordinate, and thereafter treated with GCV or saline. When the rats were treated with GCV, a significant retardation of tumor growth was observed by serial magnetic resonance imaging, although this growth retardation was less prominent than that observed with 9L glioma cells transduced with the HSVtk gene; consequently, survival was prolonged (P < .01). Tumors that received C6tk cells contained almost no HSVtk-positive cells after treatment with GCV. Rejection of allogeneic tumor cells, although possibly incomplete in the brain, can also contribute to the safety of this therapeutic strategy.
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“旁观者杀戮”会诱导细胞凋亡，并被毛喉素抑制。
DOI：
--
发表时间：
1995
期刊：
Gene therapy.
影响因子：
--
作者：
Samejima,Y;Meruelo,D
通讯作者：
Meruelo,D
影响因子：
2.7
作者：
Miller Ad;Rosman Gj
通讯作者：
Miller Ad;Rosman Gj
实验性脑肿瘤治疗中的旁观者肿瘤杀伤作用。
影响因子：
4.8
作者：
Wu,JK;Cano,WG;Meylaerts,SA;Qi,P;Vrionis,F;Cherington,V
通讯作者：
Cherington,V
DOI：
10.1073/pnas.92.24.11071
发表时间：
1995-11-21
影响因子：
11.1
作者：
FICK, J;BARKER, FG;ISRAEL, MA
通讯作者：
ISRAEL, MA