氩氦冷冻对小鼠前列腺癌血管生成影响的实验研究
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摘要
目的
     分析探讨冷冻消融治疗对前列腺癌血管生成及细胞增殖的影响,旨在评价冷冻治疗效果并为冷冻消融综合治疗中晚期前列腺癌提供实验依据。
     方法
     取C57小鼠100只,随机分两组,A、B两组均制成前列腺癌皮下移植瘤模型,A组行氩氦冷冻治疗(实验组A,n=50),荷瘤对照未行氩氦冷冻治疗(对照组B,n=50)。观察小鼠皮下肿瘤生长情况。A、B两组小鼠于冷冻术后1d、3d、5d、7d、14d分别采取肿瘤组织,每个时间点各取10只小鼠,用免疫组化方法测MVD、VEGF及Ki67。
     结果
     1接种后5天小鼠右侧腹股沟处可以扪及肿瘤长出。接种后2周,局部可形成一直径1.0~1.5cm的肿块,100只C57小鼠全部接种成功。
     2冷冻组小鼠在冷冻后MVD、VEGF及Ki67蛋白表达均出现下降,低峰值出现在3d,然后缓慢回升,与对照组相比,有显著性差异(P<0.01),冷冻组各时间点比较,经统计分析有显著性差异(P<0.05)。对照组各时间点MVD、VEGF及Ki67蛋白表达无明显变化(P>0.05)。冷冻后前列腺癌VEGF蛋白表达水平与MVD呈显著正相关(相关系数r=0.8793,P<0.01)。VEGF蛋白表达水平与ki67呈显著正相关(相关系数r=0.6921,P<0.01)。Ki67表达水平与MVD呈显著正相关(相关系数r=0.7614,P<0.01)。
     结论
     氩氦冷冻消融治疗前列腺癌后,随观察时间延长,局部肿瘤组织内MVD、VEGF、Ki67呈先降低后升高的动态变化过程,且三者呈明显正相关。而冷冻消融联合抗血管生成可能是中晚期前列腺癌综合治疗的有效手段。
Objective
     The purpose of this study was to explore the effect of Argon-Helium Cryosurgery(AHCS) on the mice of bearing RM-1 prostate cancer through detecting angiogenesis and cell proliferation in prostate cancer of mice,To analyze the effects of cryotherapy on VEGF、Ki67 protein expression and microvesel density of prostate cancer,and provide an experimental evidence on cryoablation comprehensive treatment for advanced prostate cancer.
     Materials and Methods
     A hundred mice experimental models with RM-1 prostate cancer were established,experimental mice were randomized into two group:the AHCS therapy group(group A,n=50),the tumor-bearing control group(group B,n=50).after the AHCS therapy,Peripheral tumor tissues of 50 mice were obtained from group A at 1d,3d,5d,7d,14d.at the same time,the tumor-bearing control group B(not do the AHCS therapy),tumor tissues of 50 mice were obtained from group B at 1d,3d,5d, 7d.14d.MVD,VEGF,Ki67 protein expression were detected by immunohistochemical staining at different time after the freezing.
     Results
     1.Prostate cancer cell has stable biology characteristics,and the incadence of cancer was 100%.
     2.MVD、VEGF and Ki67 protein expressions in freezing group were decreased.The lowest value was detected at the third day after freezing.The value increased slowly after that.There was no change in MVD and VEGF,Ki67 protein expressions at different time in control group(P>0.05),There were significant change in MVD,VEGF,Ki67 protein expressions at different time in freezing group(P<0.05). Correlation analysis showed suggest a positive correlation between VEGF protein expression and MVD(r=0.8793,P<0.01) suggest a positive correlation between ki67 protein expression and MVD(r=0.7614,P<0.01).suggest a positive correlation between VEGF protein expression and ki67(r=0.6921,P<0.01).
     Conclusion
     After argon-helium cryoablative treatment for prostate cancer,local tumor MVD, VEGF,Ki67 was reduced at the first day,the lowest value was detected at the third day after freezing,then increase,in the dynamic process of change,MVD,VEGF, Ki67was positively correlated.And cryoablation joint anti-angiogenesis is an effective means that may be integrated in the treatment of advanced prostate cancer.
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