The effect of high mobility group protein B1 on cryoimmunologic reaction in hormone-refractory prostate cancer: An experimental study in rats

Chang-fu Liu, Zhi Guo, T. Si, W. Xing, Fang Liu, Hai-peng Yu
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Abstract

Objective To investigate the impact of high mobility group protein B1(HGMB1) on cryoimmunology response in hormone-refractory prostate cancer(HRPC).Methods Mouse models of HRPC were established by subcutaneous injection of RM-1 prostate cancer cells,and a total of 50 tumor-bearing mice were randomly divided into control group(n = 25) and cryoablation group(n = 25).Cryoablation was applied to the tumor lesion through cryosurgery needle with 1.7mm diameter by using Endocare Argon-Helium cryosurgery system(AHCS).The number and maturation changes of dendritic cell(DC) in tumor were assessed by flow cytometry and the levels of HMGB1 in tumor tissues were determined by Western blot technology one day before cryosurgery as well as one,7,14 and 21 days after cryosurgery separately.Results In cryoablation group,the levels of HMGB1 as well as the number and maturation of DC in tumor tissues reached their highest peaks in the 7th day after AHCS,and compared with the levels determined before treatment the differences were statistically significant(P 0.05).However,in control group no significant differences in the levels of HMGB1 as well as in the number and maturation of DC in tumor tissues existed between preoperative data and post operative ones(P 0.05).The levels of HMGB1 as well as the number and maturation changes of DC in tumor tissues determined at one,7 and 14 days after cryosurgery in cryoablation group were significantly higher than those in control group (P 0.05).Correlation analysis showed that the expression levels of HMGB1 had a parallel relationship with the number of DC(r = 0.883,P 0.05) as well as with the maturation changes of DC(r = 0.997,P 0.05) in the cryoablation group.Conclusion Cryoablation therapy can make the tumor cells release large amount of HMGB1 in association with tumor cell necrosis.And the released extracellular HMGB1 plays an important role in stimulating the body to produce the tumor-specific immune response after the cryoablation therapy.
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高迁移率蛋白B1对激素难治性前列腺癌冷冻免疫反应影响的实验研究
目的探讨高迁移率组蛋白B1(HGMB1)对激素难治性前列腺癌(HRPC)冷冻免疫应答的影响。方法通过皮下注射RM-1前列腺癌细胞建立HRPC小鼠模型,将50只荷瘤小鼠随机分为对照组(n = 25)和冷冻消融组(n = 25)。采用Endocare氩氦冷冻手术系统(AHCS),用直径1.7mm的冷冻手术针对肿瘤病变进行冷冻消融。采用流式细胞术检测肿瘤中树突状细胞(DC)的数量和成熟变化,Western blot技术检测冷冻前1天、冷冻后1、7、14、21天肿瘤组织中HMGB1的水平。结果冷冻消融组AHCS后第7天肿瘤组织HMGB1水平、DC数量及成熟度均达到峰值,与治疗前比较差异有统计学意义(P < 0.05)。而对照组患者术前与术后HMGB1水平、肿瘤组织中DC数量及成熟度差异无统计学意义(P < 0.05)。冷冻消融组术后1、7、14 d肿瘤组织HMGB1水平及DC数量及成熟变化均显著高于对照组(P < 0.05)。相关分析显示,HMGB1表达水平与冷冻消融组DC数量(r = 0.883,P 0.05)及DC成熟度变化(r = 0.997,P 0.05)呈平行关系。结论冷冻消融治疗可使肿瘤细胞大量释放HMGB1,并伴有肿瘤细胞坏死。细胞外释放的HMGB1在冷冻消融治疗后刺激机体产生肿瘤特异性免疫应答中起重要作用。
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Journal of Interventional Radiology
Journal of Interventional Radiology Medicine-Radiology, Nuclear Medicine and Imaging
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