Therapeutic effect of gene-therapy in combination with local X-irradiation in a mouse malignant melanoma model

Therapeutic effect of gene-therapy in combination with local X-irradiation in a mouse malignant melanoma model
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基因治疗联合局部 X 射线照射对小鼠恶性黑色素瘤模型的治疗效果。

DOI:
10.1016/j.bbrc.2005.03.070
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发表时间:
2005-05-13
影响因子:
3.1
通讯作者:
Liu, SZ
Liu, SZ
中科院分区:
生物学4区
文献类型:
--
作者:
Jin, GH;Jin, SZ;Liu, SZ

文献摘要

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构建了Egr-1启动子下游含有mIL-18和B7.1基因的质粒,并将其用于植入B16细胞的C57BL/6J小鼠恶性黑色素瘤的基因放射治疗,并探讨其治疗效果的免疫学机制。用质粒pEgr-IL-18-B7.1加局部X射线照射的治疗比单独用放射线、单独的pEgr-IL-18-B7.1或单基因pEgr-IL-18(或pEgr-B7.1)联合局部X射线照射的治疗更有效地抑制肿瘤生长。研究发现,用 pEgr-IL-18-B7.1 加局部 X 射线照射治疗的荷瘤小鼠的抗癌免疫力显着上调。 IL-18在体外对恶性黑色素瘤细胞无直接杀伤作用,pEgr-IL-18-B7.1与局部X射线联合治疗的机制显然与局部X射线照射对肿瘤细胞的直接作用外,还与通过增加IL-18分泌刺激宿主抗癌免疫以及增加肿瘤细胞表面B7.1表达上调肿瘤细胞的免疫原性有关。 (c) 2005 年,爱思唯尔公司出版。
Plasmid containing mIL-18 and B7.1 genes downstream of Egr-1 promoter was constructed and used in gene-radiotherapy on malignant melanoma in C57BL/6J mice implanted with B16 cells followed by exploration of the immunologic mechanism of the therapeutic effect. The treatment with plasmid pEgr-IL-18-B7.1 plus local X-irradiation showed more effective suppression of tumor growth than the treatment with radiation alone, pEgr-IL-18-B7.1 alone, or single gene pEgr-IL-18 (or pEgr-B7.1) combined with local X-irradiation. Anticancer immunity was found to be significantly upregulated in tumor-bearing mice treated with pEgr-IL-18-B7.1 plus local X-irradiation. IL-18 showed no direct killing effect on malignant melanoma cells in vitro, and the mechanism of the combined therapy with pEgr-IL-18-B7.1 and local X-irradiation was apparently related with the stimulation of host anticancer immunity by increased secretion of IL-18 and upregulated immunogenicity of the tumor cells by increased expression of B7.1 on their surface in addition to the direct effect of local X-irradiation on the tumor cells. (c) 2005 Published by Elsevier Inc.