腹腔注射5-氟尿嘧啶治疗腹膜假黏液瘤的人源异种移植模型  

Experimental study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil to treat PDX model of pseudomyxoma peritonei

作　　者：林育林 张珏 闫风彩 蒋茜 马茹 杨智冉 李雁 Lin Yulin;Zhang Jue;Yan Fengcai;Jiang Xi;Ma Ru;Yang Zhiran;Li Yan(Department of Peritoneal Cancer Surgery,Beijing Shijitan Hospital affiliated to Capital Medical University,Beijing 100038,China;Department of Pathology,Beijing Shijitan Hospital affiliated to Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院腹膜肿瘤外科,北京100038 [2]首都医科大学附属北京世纪坛医院病理科,北京100038

出　　处：《中华实验外科杂志》2019年第10期1798-1801,共4页Chinese Journal of Experimental Surgery

基　　金：北京市自然科学基金(7172108);北京市医院管理局"登峰"人才培养计划(DFL20180701);北京市科学技术委员会首都临床特色应用研究(Z161100000516077);北京市医院管理局北京市优秀人才培养资助集体项目(2017400003235J007);首都医科大学附属北京世纪坛医院重点学科建设项目(2016fmzlwk).

摘　　要：目的以腹膜假黏液瘤(PMP)原位人源异种移植(PDX)模型为研究对象,探讨腹腔注射5-氟尿嘧啶(5-Fu)的疗效及安全性.方法将1例PMP肿瘤标本接种于BALB/c-nu小鼠,建立PDX模型,随机等分为空白对照组(无任何处理)、溶媒对照组(腹腔注射生理盐水0.2ml)和治疗组(腹腔注射5-Fu,50 mg/kg,0.2 ml).根据实验性腹膜癌指数(ePCI)和病理学检查评估疗效和不良反应.结果成功建立PMP PDX模型,病理诊断为腹膜高级别黏液癌伴印戒细胞(HMCP-S).治疗组ePCI评分显著低于空白对照组、溶媒对照组[(0.9±1.2)分比(3.6±1.7)分比(2.7±1.1)分,F=9.253,P<0.01].病理学检查示治疗组明显肿瘤坏死、裂解,黏液湖漂浮大量均质、嗜酸性细胞碎片,印戒细胞减少;治疗组Ki-67阳性率显著低于空白对照组和溶媒对照组[(57.3±15.1)%比(72.2±15.1)%比(70.0±14.0)%,F=4.923,P<0.05].毒性研究中,治疗组体重显著低于空白对照组和溶媒对照组[(19.7±2.8)g比(22.7±1.8)g比(21.9±1.7)g,F=4.654,P<0.05].治疗组1只裸小鼠死亡(10.0%),脾淤血肿大(88.9%),肝脏淋巴细胞聚集(77.8%),胆小管增生、阻塞(22.2%),肝小叶胆汁淤积(100.0%),嗜酸性小体(55.6%)形成.结论通过PMP PDX模型证实,腹腔注射5-Fu可抑制肿瘤生长播散,降低ePCI评分、Ki-67阳性率,主要器官毒性为肝损害.Objective To evaluate the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil (5-Fu) in patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP). Methods One PMP tumor from surgery was used to establish PMP PDX models, which were equally randomized into control (no treatment), vehicle (normal saline, 0.2 ml) and treatment (5-Fu, 50 mg/kg, 0.2 ml) groups. Experimental peritoneal cancer index (ePCI) score, body weight, and pathological examination were performed to evaluate the efficacy and toxicity. Results PDX models replicating human PMP were established and diagnosed as high grade mucinous carcinoma peritonei with signet ring cells. Average ePCI score of treatment group was significantly lower than control and vehicle groups [(0.9±1.2) points vs.(3.6±1.7) points vs.(2.7±1.1) points, F=9.253, P<0.01]. Histopathological study revealed obvious tumor necrosis and reduced signet ring cells in the treatment group. The Ki-67 label index of treatment group was significantly lower than control group and vehicle group [(57.3±15.1)% vs.(72.2±15.1)% vs.(70.0±14.0)%, F=4.923, P<0.05]. The body weight of treatment group was significantly lower than control group and vehicle group [(19.7±2.8) g vs.(22.7±1.8) g vs.(21.9±1.7) g, F=4.654, P<0.05]. Major toxicities in the treatment group were animal death (10.0%), congestive splenomegaly (88.9%), lymphocyte accumulation (77.8%), bile canaliculus hyperplasia and obstruction (22.2%), cholestasis (100.0%), and acidophilic body (55.6%) in the liver. Conclusion In the PDX model of human PMP, intraperitoneal injection of 5-Fu could inhibit tumor proliferation and progression, with lowered ePCI score and reduced Ki-67, and toxicity was mainly on liver.

关 键 词：腹膜假黏液瘤 原位人源异种移模型 5-氟尿嘧啶 腹腔注射 器官毒性 

分 类 号：R735.5[医药卫生—肿瘤] R-332[医药卫生—临床医学]