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树突状细胞与反义TGF-β1基因修饰的胶质瘤细胞融合瘤苗治疗脑胶质瘤的实验研究

Experimental study of vaccination with fusions of dendritic cells and C6 glioma cells expressing TGF-beta anti-sense gene in the treatment of intracranial gliomas

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【作者】 刘福生金贵善历俊华林松王忠诚

【Author】 LIU Fu-sheng, JIN Gui-shan, LI Jun-hua, et al. Beijing Neurosurgical Institute, Beijing 100050, China

【机构】 北京市神经外科研究所北京市神经外科研究所

【摘要】 目的研究脑胶质瘤的免疫治疗。方法采用骨髓来源的干细胞经IL-4与GM-CSF 培养的树突状细胞与反义TGF-β1基因修饰的C6胶质瘤细胞进行融合,后鼠脑内注射进行动物实验。实验分为四组:Ⅰ组:阳性对照组:C6细胞(每只动物注射细胞数1×106);Ⅱ组:转染反义 TGF-β1的C6细胞与树突状细胞相融合的融合细胞(每只动物注射1×105 C6细胞与1×106个树突状细胞的融合细胞)和C6细胞(1×106);Ⅲ组:阴性对照组,注射相同体积IMDM培养液。观察动物的组织学、生存期及图像分析肿瘤的肿瘤坏死面积及肿瘤面积。结果Ⅰ组:所有动物20d内全部死亡;Ⅱ组:动物存活59d无死亡;Ⅲ组:所有动物实验过程中均存活。Ⅰ组:图像分析仪下肿瘤面积为100%;Ⅱ组:仅见有少量的肿瘤细胞,肿瘤周围神经元减少、胶质增生,其肿瘤面积与Ⅰ组相比占整个视野的5.01%-6.20%,少见肿瘤坏死。统计学处理:Ⅱ组与其他各组比较P<0.01。结论树突状细胞与反义TGF-β1基因修饰的胶质瘤细胞融合瘤苗能够延长动物的存活期,为将来采用基因修饰的脑胶质瘤融合瘤苗治疗脑胶质瘤提供帮助.

【Abstract】 Objective To investigate the immunotherapy efficacy of fusion cells (dendritic-C6 cells) in the treatment of intracranial gliomas. Methods Dendritic cells were isolated from rat bone-marrow precursors stimulated in vitro with granulocyte -macrophage colony -stimulating factor ( GM -CSF) and Interleukin-4 (IL-4) , C6 cells originally from a rat glioblastoma were transfected with TGF -beta antisense gene. Fusions of dendritic cells and C6 cells were made by PEG. All experimental rats were divided into 3 groups at random. C6 cells (group Ⅰ ) , dendritic-C6 fusion cells and C6 cells (group Ⅱ ) , were injected into right parietal lobe region respectively in different groups with stereotaxic technique, the negative control group (group Ⅲ ) was injected with IMDM medium only. Histology, survival time and tumor necrosis were evaluated. Results Compared with the rats that received C6 cells (survival time is less than 20 days after injection) , the rats injected with fusion cells and C6 cells got a more prolonged life span (more than 59 days) , as well as less tumor region (5.01%-6.2%) , no tumor necrosis, surrounding had some glias; while group Ⅰ was 100% respectively) , all rats were survived and no necrosis was observed in negative control group. Statistics indicated that group Ⅱ had significant difference than other groups. Conclusions Therapeutic effect of dendritic-C6 fusion cells could prolong life span of rats and indicates that this fusion cell vaccine could provide a new method of immunotherapy for gliomas.

【基金】 北京市自然科学基金(编号:7982004)
  • 【文献出处】 中华神经外科杂志 ,Chinese Journal of Neurosurgery , 编辑部邮箱 ,2006年01期
  • 【分类号】R739.41
  • 【被引频次】24
  • 【下载频次】355
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