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作 者:黄建华[1] 王瑶[1] 吕海燕[1] 郭佳[1] 郭业磊[1] 马林[2]
机构地区:[1]解放军总医院肿瘤免疫治疗研究中心,北京100853 [2]解放军总医院放射治疗科,北京100853
出 处:《中国实验动物学报》2008年第5期346-349,I0002,共5页Acta Laboratorium Animalis Scientia Sinica
基 金:北京市自然科学基金资助项目(编号:7042060)
摘 要:目的研究放疗增强DC疫苗治疗小鼠肾癌的作用机理。方法Renca肾癌细胞制作BALB/c小鼠皮下移植瘤模型,分别用单纯放疗、单纯DC和DC瘤内注射联合放疗等方法治疗,第28天牺牲小鼠。体外培养2×106Renca肾癌细胞,经20 Gy X射线单次照射培养24 h后,收获细胞。提取细胞和肿瘤组织蛋白,免疫组化和免疫印迹法检测治疗后肿瘤组织中TNF-α、CD3、CD11和F4/80蛋白的表达水平。结果DC瘤内注射联合放疗有效抑制肾癌细胞在BALB/c小鼠体内生长,局部放疗明显增加了肿瘤组织内TNF-α表达水平,体外培养的Renca肾癌细胞经放射线处理后TNF-α表达明显上调。结论放射线能够促进肿瘤细胞分泌TNF-α,瘤内注射DC联合放疗的增效作用与肿瘤局部产生的TNF-α表达上调密切相关。Objective To investigate the mechanism and efficacy of dendritic cell (DC)-based immunotherapy in combination with radiotherapy (RT) for renal carcinoma. Methods Renal carcinoma-bearing mice were treated with intratumoral (i. t. ) injection of bone marrow-derived unloaded DCs in combination with local fraetionated tumor irradiation, RT alone and DC alone. The mice were euthanized on day 28. Cultured Renca cells were exposed to a single radiation dose of 20 Gy after culture for 24 h. The expression of TNF-α, CD3, CD11 and F4/80 proteins in tumors and Renca cells were assayed by Western blot and immunohistochemieal staining. Results The intratumoral DC vaccine plus radiotherapy led to an effective tumor rejection in the renal cell carcinoma model. The expression of TNF-α in DC plus RT treated Renca tumor and cultured Renca cells after exposure to radiation was significantly elevated. Conclusion Significantly augmented therapeutic efficacy by DC combined with RT is associated with an increased local production of TNF-α
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