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背景与目的:恶性胶质瘤预后差,有必要探索新方法提高疗效。本研究用Ad-rhTNF-α基因治疗联合放疗治疗大鼠皮下C6胶质瘤,评估其疗效和安全性。方法:基因工程技术构建Ad-rhTNF-α后,建立大鼠皮下胶质瘤模型,联合治疗组瘤内注射Ad-rhTNF-α,24h后行X线加速器放疗,各对照组作相应处理。放疗5天后处死所有大鼠进行形态学研究。结果:联合治疗组肿瘤体积最小,有丝分裂细胞数量最少,坏死区域最广,凋亡小体最为多见。联合治疗组外周血Th/Ts比值降低(P<0.05),NK细胞数量增多(P<0.05),体内免疫机制上调,效应细胞数量增多,免疫活性增强。各组体重与全血细胞分析的各项指标很接近。结论:Ad-rhTNF-α基因治疗放射联合治疗抗大鼠C6胶质瘤肿瘤作用明显优于单纯放疗和基因治疗,并且在目前剂量下是安全的。
BACKGROUND & OBJECTIVE: Malignant gliomas have a poor prognosis. It is necessary to explore new ways to improve the curative effect. In this study, Ad-rhTNF-α gene therapy combined with radiotherapy of subcutaneous C6 glioma in rats to evaluate its efficacy and safety. Methods: Ad-rhTNF-α was constructed by gene engineering. The rat model of subcutaneous glioma was established. Ad-rhTNF-α was injected intratumorally in the combined treatment group and treated with X-ray accelerator 24h after treatment. The control groups were treated accordingly. Five days after radiotherapy, all rats were sacrificed for morphological studies. Results: The combined treatment group had the smallest tumor volume, the least number of mitotic cells, the most extensive necrosis area and the most apoptotic body. The Th / Ts ratio in the peripheral blood was decreased (P <0.05) and the number of NK cells was increased in the combined treatment group (P <0.05). The immune mechanism was upregulated in the combination therapy group, with an increase in the number of effector cells and an increase in the immunological activity. Each group of body weight and blood cell analysis of the various indicators are close. CONCLUSION: Ad-rhTNF-α gene therapy combined with radiotherapy in the treatment of rat C6 glioma tumor is obviously superior to radiotherapy alone and gene therapy and is safe at the current dose.