超声造影评价裸鼠咽鳞癌顺铂化疗疗效及肿瘤血管生成的实验研究

An experimental study of contrast-enhanced ultrasound in evaluating the efficacy of cisplatin chemotherapy and tumor angiogenesis in pharyngeal squamous cell carcinoma in nude mice

目的探讨超声造影(CEUS)定量参数评价裸鼠咽鳞癌移植瘤模型顺铂化疗疗效及肿瘤血管生成的可行性。方法建立FaDu人咽鳞癌裸鼠移植瘤模型,随机分为生理盐水对照组、低中高剂量顺铂组[3、4、5 mg/(kg·d)],每组5只,行CEUS检查,测定各组移植瘤体积和CEUS定量参数:峰值强度(PI)、曲线下面积(AUC)、达峰时间(TTP)、到达时间(AT)。采用免疫组化法检测肿瘤微血管密度(MVD),进行组间比较及相关性分析。结果各组裸鼠移植瘤的治疗后肿瘤体积、CEUS定量参数和MVD差异均有统计学意义(均P<0.05)。且在本实验条件下(肿瘤初始体积大小约100 mm^(3)),PI、AUC、肿瘤体积与MVD均呈正相关(r=0.708、0.866、0.752,均P<0.05)。PI、AUC与肿瘤体积均呈正相关(r=0.730、0.866,均P<0.05)。结论超声造影定量参数PI、AUC和TTP可评价裸鼠咽鳞癌模型顺铂化疗疗效,且PI和AUC与肿瘤MVD密切相关,为评价咽鳞癌的血管生成及肿瘤生长提供了重要信息。

Objective To investigate the feasibility of quantitative parameters of contrast-enhanced ultrasound(CEUS)in evaluating the efficacy of cisplatin chemotherapy and tumor angiogenesis in the nude mouse pharyngeal squamous cell carcinoma xenograft model.Methods A nude mouse xenograft model of human pharyngeal squamous cell carcinoma(FaDu)was established and randomly divided into a saline control group and cisplatin low,medium,and high-dose chemotherapy groups[3,4,5 mg/(kg·d),respectively].Contrast-enhanced ultrasound(CEUS)examination was performed to measure the tumor volume and CEUS quantitative parameters,including peak intensity(PI),area under the curve(AUC),time to peak(TTP),and arrival time(AT).Immunohistochemistry was used to detect tumor microvessel density(MVD)and conduct intergroup comparisons and correlation analysis.Results There were significant differences in tumor volume,CEUS quantitative parameters,and MVD among the various groups of nude mice with xenograft tumors(all P<0.05).Under the experimental conditions of this study(initial tumor volume approximately 100 mm^(3)),PI,AUC,and tumor volume were positively correlated with MVD(r=0.708,0.866,0.752,all P<0.05).PI and AUC were also positively correlated with tumor volume(r=0.730,0.866,both P<0.05).Conclusion Quantitative CEUS parameters,such as PI,AUC,and TTP,can be used to evaluate the efficacy of cisplatin chemotherapy in a nude mouse model of pharyngeal squamous cell carcinoma.Additionally,PI and AUC are closely correlated with tumor MVD,providing important information for assessing angiogenesis and tumor growth in pharyngeal squamous cell carcinoma.