魏道严,戴冰冰,王中和,等.腺病毒载体介导mIL-12基因治疗联合放射治疗小鼠肝癌的研究[J].中华放射医学与防护杂志,2001,21(4):279-281.WEI Daoyan,DAI Bingbing,WANG Zhonghe,et al.Adenovirus-mediated IL-12 gene therapy in combination with radiotherapy for murine liver cancer[J].Chin J Radiol Med Prot,2001,21(4):279-281
腺病毒载体介导mIL-12基因治疗联合放射治疗小鼠肝癌的研究
Adenovirus-mediated IL-12 gene therapy in combination with radiotherapy for murine liver cancer
投稿时间:2001-01-05  
DOI:
中文关键词:  肝肿瘤  腺病毒  白介素-12  基因治疗  放射治疗
英文关键词:Liver cancer  Adenovirus  Interleukin-12  Gene therapy  Radiotherapy
基金项目:国家863高技术计划基金资助项目(863012452);国家自然科学重点课题基金资助项目(39710440)
作者单位
魏道严 200025上海第二医科大学人类基因治疗研究中心 
戴冰冰 200025上海第二医科大学人类基因治疗研究中心 
王中和 上海第九人民医院放疗科 
陈诗书 200025上海第二医科大学人类基因治疗研究中心 
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中文摘要:
      目的 观察腺病毒介导白介素-12基因治疗联合放射治疗协同抗小鼠肝癌作用.方法 荷肝癌动物模型,肿瘤局部γ射线照射后,瘤内注射AdmIL-12腺病毒.取组织标本进行ELISA及CTL活性检测、免疫组化染色等分析.结果 联合治疗小鼠肿瘤生长受到抑制,体积明显缩小,并可使 5 0 %的小鼠肿瘤完全消退,疗效显着优于单纯照射组和瘤内注射AdmIL-12及其他对照组(P <0.0 1).而单纯瘤内注射AdmIL-12组的疗效并不优于单纯照射组 (P >0.0 5).联合治疗组小鼠血清和脾细胞的培养上清中可见IFN-γ水平的显着提高,并诱导产生特异性的CTL活性.免疫组化结果显示,联合治疗组肿瘤组织中可见有大量CD4+ 、CD8+ 阳性淋巴细胞的浸润.结论 腺病毒介导白介素 12基因治疗与放射治疗的联合具有协同抗肿瘤作用,并诱导产生特异性抗肿瘤免疫反应.
英文摘要:
      Objective To investigate the synergistic antitumor effects of adenovirus mediated IL-12 gene therapy in combination with radiotherapy in mice bearing liver cancer. Methods Balb/c mice bearing liver cancer received the treatment at day 1 with tumor local irradiation (TLI) of 20 Gy or mask irradiation when tumor size reached 0.6-1.0 cm. Within 1 hour after irradiation,adenovirus containing IL-12 gene or PBS was intratumorally injected once a week. Forty-eight hours after the second injection,IFN-γ levels in sera and the supernatant of cultured spleen cells were assayed by ELISA, CTL activity of spleen cells was measured by 3H-TdR release assay,and phenotypes of tumor infiltrating lymphocytes were analysed by immunohistochemical staining. Results The growth of tumors in animals treated with a combination of IL-12 gene therapy and TLI was inhibited more significantly than those with either single treatment (P <0.01).Tumors of about 50% mice with the combined treatment were eradicated and there was no tumor developed after rechallenged with subcutaneous injection of MM45T.Li cells.lmmunohistochemical staining showed that combined treatment of IL-12 gene therapy and TLI could induce abundant CD4+ and CD8+ lymphocyte infiltration and tumor specific cytolytic activities, and the levels of IFN-γ in sera were higher in IL-12 gene therapy and IL-12 gene therapy combined with TLI groups. Conclusion These results suggest that IL-12 gene therapy combined with radiotherapy is more effective than both single treatment modalities and can induce specific antitumor immunoreponse greatly.
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