动态三维超声造影评价瑞格非尼抑制兔肝VX_(2)残癌增殖的实验研究

Experimental study of dynamic three-dimensional contrast-enhanced ultrasound in evaluating the inhibitory effect of regorafenib on the proliferation of incomplete ablation residual liver VX_(2)tumor

目的:观察瑞格非尼对不全消融残癌的抑制作用并探讨动态三维超声造影(three-dimensional contrast-enhanced ultrasound,3D-CEUS)评估靶向治疗反应的可行性。方法:构建兔VX_(2)肝原位种植瘤模型及不全消融模型,随机将实验兔分为4组(n=5):不全消融组(A组)、不全消融+靶向治疗组(B组)、靶向治疗组(C组)、对照组(D组)。在不全消融治疗前当天及治疗后7、14、21、28 d进行3D-CEUS检查并进行在机定量参数分析,实验结束后取出VX_(2)肿瘤行细胞增殖指数(Ki-67)、CD34免疫组织化学染色,计算微血管密度(microvessel density,MVD)并比较各组间差异。结果:在治疗后21和28 d,B组和C组的峰值强度(peak intensity,PI)显著低于治疗前(P值分别为0.046,0.033);而且,B组和C组的PI与D组相比差异有统计学意义(P值分别为0.027,0.031)。在治疗后28 d,B组和C组的上升支斜率(S)显著低于同时期对照组(P值分别为0.035,0.014);而且B组与A组相比差异有统计学意义(P=0.027)。治疗后28 d,各组肿瘤组织Ki-67增殖指数、MVD计数差异无统计学意义(P>0.05)结论:3D-CEUS定量分析技术可反映瑞格非尼抑制肝VX_(2)原位种植瘤残癌增殖的治疗效果。

Objective:To observe the feasibility of three-dimensional contrast-enhanced ultrasound(3D-CEUS)in evaluating the inhibitory effect of regorafenib on incomplete ablation of residual cancer.Methods:The rabbits were randomly divided into 4 groups(n=5):incomplete ablation group(group A),incomplete ablation+targeted therapy group(group B),targeted therapy group(group C),and control group(group D).3D-CEUS was performed on the day before treatment and 7,14,21,28 d after treatment,and quantitative parameters were analyzed in vivo.VX_(2) tumors were taken out at the end of the experiment for cell proliferation index(Ki-67)and CD34 immunohistochemical staining,and microvessel density(MVD)was calculated.Results:At 21 and 28 days after treatment,the peak intensity(PI)of group B and C was significantly lower than that before treatment(P=0.046,0.033,respectively).Moreover,the PI of group B and group C were significantly different from that of group D(P=0.027,0.031,respectively).At 28 d after treatment,the ascending slope(S)of group B and group C was significantly lower than that of the control group(P=0.035,0.014,respectively).There was significant difference between group B and group A(P=0.027).At 28 d after treatment,there was no significant difference in Ki-67 proliferation index and MVD among the three groups(P>0.05).Conclusion:Quantitative analysis parameters of 3D-CEUS can reflect the efficacy of regorafenib in inhibiting the proliferation of residual cancer after incomplete ablation of VX_(2) in situ orthotopic tumor.