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使用 HSVtk 基因转导间充质干细胞进行脑胶质瘤基因治疗时的药物作用时间。

Timing of ganciclovir administration in glioma gene therapy using HSVtk gene-transduced mesenchymal stem cells.

机构信息

Department of Neurosurgery, Hamamatsu University School of Medicine, Handayama, Higashi-ku, Hamamatsu, Japan.

出版信息

Cancer Genomics Proteomics. 2011 Sep-Oct;8(5):245-50.

PMID:21980039
Abstract

BACKGROUND

An established C6 glioma was successfully treated with intratumoral injection of mesenchymal stem cells transduced with HSVtk gene (MSCtk) and systemic administration of ganciclovir (GCV). The best timing of GCV administration after the MSCtk implantation was studied.

MATERIALS AND METHODS

GCV administration was started from 2 days before and 1, 3 and 7 days after the MSCtk administration under both in vitro and in vivo conditions.

RESULTS

The C6 cells were completely eradicated in vitro when GCV administration was started from day -2, 1, and 3. Animals with intracranial tumor survived longer when GCV was administered earlier after MSCtk administration. This may, mainly, reflect the difference in the MSCtk/C6 ratio at the time of GCV administration because this ratio drastically decreases during the delay of GCV administration.

CONCLUSION

When using a slowly growing vector cell as MSCtk, GCV should be administered soon after MSCtk implantation.

摘要

背景

已建立的 C6 神经胶质瘤通过间质干细胞转导单纯疱疹病毒胸苷激酶基因(MSCtk)的肿瘤内注射和更昔洛韦(GCV)的全身给药成功治疗。研究了 MSCtk 植入后 GCV 给药的最佳时间。

材料与方法

在体外和体内条件下,GCV 给药分别在 MSCtk 给药前 2 天、1 天、3 天和 7 天开始。

结果

当 GCV 给药在第 -2、1 和 3 天开始时,体外的 C6 细胞被完全根除。在 MSCtk 给药后更早给予 GCV 的颅内肿瘤动物存活时间更长。这主要可能反映了 GCV 给药时 MSCtk/C6 比值的差异,因为随着 GCV 给药的延迟,该比值急剧下降。

结论

当使用生长缓慢的载体细胞作为 MSCtk 时,GCV 应在 MSCtk 植入后尽快给予。

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