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pEgr-TNFα质粒的构建及基因-放射治疗小鼠黑色素瘤的实验研究 被引量:10

Construction of pEgr-TNFα plasmid and experimental study on the effect of gene-radiotherapy on mouse melanoma
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摘要 目的 研究pEgr TNFα重组质粒的构建及其联合放射治疗抑制小鼠黑色素瘤的效果和对免疫系统的影响。方法 将TNFαcDNA插入pcDNA3.1质粒的多克隆位点 ,用Egr 1的启动子替代pcDNA3.1质粒的CMV启动子 ,构建成pEgr TNFα重组质粒 ;建立小鼠B16黑色素瘤动物模型 ,肿瘤局部注射脂质体包裹的质粒 ,在不同时间测量肿瘤体积 ,并检测照后 15d部分免疫学指标。结果 pEgr TNFα基因 放射联合治疗后第 3~ 15天 ,肿瘤生长速率明显低于单纯照射组、单纯基因治疗组和空质粒对照组。小鼠脾脏NK细胞毒活性、IL 2分泌活性、腹腔巨噬细胞TNFα和IL 1β活性均明显高于单纯放疗组。结论 pEgr TNFα基因 放射联合治疗抗肿瘤作用明显优于单纯放疗组和单纯基因治疗组 ,同时可以减轻放疗对机体免疫功能的损伤。 ObjectiveThe pEgr-TNFα plasmid was constructed to investigate the effect of gene-radiotherapy on melanoma and host immune system. MethodspEgr-TNFα plasmids were constructed and injected into tumor tissue, 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different timepoints was record and immunologic parameters were detected 15 days later. ResultsFrom 3 to 15 d after pEgr-TNFα gene-radiotherapy the tumor growth was significantly slower than irradiation or genetherapy alone. NK activity, IL-2, TNFα and IL-1β secretion activities of pEgr-TNFα gene-radiotherapy group and pEgr-TNFα gene group were higher than those of irradiation alone group significantly. ConclusionThe anti-tumor effect of pEgr-TNFα gene-radiotherapy is better than that of either one applied solely, and it can alleviate the lesion caused by radiation therapy.
出处 《中华肿瘤杂志》 CAS CSCD 北大核心 2004年第3期143-145,共3页 Chinese Journal of Oncology
基金 国家自然科学基金资助项目 (3 9970 2 2 9)
关键词 pEgr-TNFα重组质粒 基因治疗 放射治疗 黑色素瘤 小鼠 免疫功能 pEgr-TNFα plasmid X-ray irradiation B16 melanoma Gene therapy Radiotherapy
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  • 1Avalosse B, Dupont F, Bumy A. Gene therapy for cancer. Curt Opin Oncol, 1995, 7: 94-100.
  • 2Datta R, Rubin E, Sukhatme V, et al. Ionizing radiation activates transcription of Egr-1 gene via CArG elements. Proc Nat Aead Sci USA,1992, 89: 10149-10153.
  • 3Mauceri HJ, Hanna NN, Wayne ID , et al. Tumor necrosis factor alpha(TNF alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculaane. Cancer Res, 1996, 56: 4311-4314.
  • 4Seung LP, Mauceri HI, Beckett MA, et al. Genetic radiotherapy overcomes tumor resistance to cytotoxic agents. Cancer Res, 1995, 55:5561-5565.
  • 5Gupta VK, Park JO, Jaskowiak NT, et al. Combined gene therapy and ionizing radiation is a novel approach to treat human esophageal adenocarcinoma. Ann Surg Oncol, 2002, 9: 500-504.

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