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tk基因治疗脑胶质瘤时的免疫反应与旁观者效应的关系

Relation between immune response and bystander effect when using tk gene to treat therapy glioma
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摘要 目的 探讨tk基因 (thymidinekinasegene)治疗脑胶质瘤时的免疫反应与旁观者效应的关系。方法 将C6 tk+与C6 tk 按 0 %tk+,10 %tk+,30 %tk+,5 0 %tk+,10 0 %tk+5种比例混合 ,接种于SD鼠右侧顶叶 ,7d后腹腔注射GCV(更昔洛韦 ) ,剂量为 30mg/kg/d ,共 10d。细胞接种 3周后 ,处死动物 ,计算成瘤率 ,作病理检查 ,并作CD4 +、CD8+的免疫组化染色。结果  5 0 %及 10 0 %C6 tk+组的成瘤率明显小于其余3组 (P <0 .0 5 ) ,病理检查发现 5 0 %及 10 0 %tk+组有淋巴细胞及浆细胞浸润。免疫组化显示每一组之间均有差异 ,提示有免疫反应存在。结论 tk基因治疗脑胶质瘤时 ,可激起机体内的免疫反应 ,增强抗肿瘤作用 。 Objective To investigate the relation between immune response and bystander effect when using tk gene for therapy of glioma.Methods tk + and tk \| C6 cells were mixed at the ratios of 0% tk + , 10% tk + , 30%tk + , 50%tk + , 100%tk + .The mixed cells were implanted directly to the right parietal lobe of the SD rats. Seven days after cell implanted, all rats were given GCV 30mg/kg/d for 10 days. Three weeks after cell implanted all rats were killed. The rate of tumor growth, the pathological and immunohistological characters of tumor tissues were measured.Results The rate of tumor growth of 50% and 100%C 6 tk + groups were significantly lower than those of the other three groups( P <0.05). Pathological study showed a significant T lymphocytes and plasmacytes infiltration phenomena in tumor tissues of 50% and 100%C 6 tk + groups. Immunohistological analysis displayed significant differences among all groups.Conclusion Immune response can be induced in the tk/GCV therapy of glioma and it can enhance the efficiency of antitumor. It may be one of the mechanisms of bystander effect.
出处 《肿瘤防治研究》 CAS CSCD 2002年第4期280-282,共3页 Cancer Research on Prevention and Treatment
基金 湖北省科委自然科学基金资助 (SJ :97J0 6 9)
关键词 TK基因 脑胶质瘤 免疫反应 旁观者效应 基因疗法 实验研究 tk gene Gene therapy Glioma Bystander effect Immune response
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  • 1[1]Shinoura N, Chen L, Wani MA, et al.Protein and Messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy[J]. J Neurosurg, 1996,84(5):839-845.
  • 2[2]Vile RG, Castleden S, Marshall J. Generation of a an anti-tumor immunerespones in a non-immunogenic tumor:HSVtk lilling in vivo stimulates a mononuclear cell infiltrate and a Thi-like profile of intramoral cytokine expression[J]. Inl J Cancer, 1997,71(2):267-274.
  • 3[3]Mullen CA, Anderson L, Woods K, et al. Ganciclovir chemoablation ofherpes thymidine kinase suicide Gene-modified tumors produces tumor necrosis and induces systemic immune responses[J]. Hum Gene Ther, 1998,9(14):2019-2030.

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