采用瘤内转导胸苷激酶逆转录病毒包装细胞注射及更昔洛韦治疗对大鼠BT4C恶性胶质瘤进行基因治疗的疗效较低。

Low efficacy of gene therapy for rat BT4C malignant glioma using intra-tumoural transduction with thymidine kinase retrovirus packaging cell injections and ganciclovir treatment.

作者信息

Sandmair A M, Loimas S, Poptani H, Vainio P, Vanninen R, Turunen M, Tyynelä K, Vapalahti M, Ylä-Herttuala S

机构信息

A. I. Virtanen Institute, University of Kuopio, Finland.

出版信息

Acta Neurochir (Wien). 1999;141(8):867-72; discussion 872-3. doi: 10.1007/s007010050389.

DOI:10.1007/s007010050389

PMID:10536724

Abstract

BACKGROUND

The purpose of this study was to test the use of Herpes Simplex virus thymidine kinase (HSVtk) retrovirus packaging cell injections in the treatment of malignant brain tumours.

METHODS

Therapeutic effect and tissue responses were examined in vivo in a syngeneic BT4C rat glioma model after HSVtk-producing PA317 packaging cell injections and intraperitoneal ganciclovir (GCV) medication. MRI was used to visualise the tumours before and after the treatment. Immunohistochemical stainings were performed to study astroglia and microglia responses and apoptosis-mediated cell death.

RESULTS

The results suggest that only a limited treatment effect can be achieved with HSVtk packaging cell injections with no prolonged survival rates. Histological examination showed a strong astroglia response but only a modest microglia response after the treatment. HSVtk and GCV-induced cell death was at least partially mediated by apoptosis. It is concluded that HSVtk packaging cell injections and GCV treatment do not lead to eradication of malignant cells in a syngeneic BT4C rat glioma model. The lack of efficacy is most likely due to low gene transfer efficiency and limited life span of the injected packaging cell inside the tumours.

CONCLUSIONS

Improvements in gene transfer efficiency, and stimulation of immunoresponse against tumour cells might lead to a more effective therapeutic response in vivo.

摘要

背景

本研究的目的是测试单纯疱疹病毒胸苷激酶（HSVtk）逆转录病毒包装细胞注射在恶性脑肿瘤治疗中的应用。

方法

在同基因BT4C大鼠胶质瘤模型中，注射产生HSVtk的PA317包装细胞并腹腔注射更昔洛韦（GCV）后，在体内检测治疗效果和组织反应。使用MRI在治疗前后对肿瘤进行可视化。进行免疫组织化学染色以研究星形胶质细胞和小胶质细胞反应以及凋亡介导的细胞死亡。

结果

结果表明，HSVtk包装细胞注射只能取得有限的治疗效果，且生存率没有延长。组织学检查显示治疗后星形胶质细胞反应强烈，但小胶质细胞反应适度。HSVtk和GCV诱导的细胞死亡至少部分由凋亡介导。得出的结论是，在同基因BT4C大鼠胶质瘤模型中，HSVtk包装细胞注射和GCV治疗不能根除恶性细胞。疗效不佳很可能是由于基因转移效率低以及注射的包装细胞在肿瘤内的寿命有限。