医学
氟尿嘧啶
体内
病理
毒性
癌症研究
细胞凋亡
内科学
胃肠病学
癌症
腹膜腔
化疗
腺癌
腹膜
腹水
腹膜癌病
作者
Yulin Lin,Jue Zhang,Fengcai Yan,Xi Jiang,Ru Ma,Zhi-Ran Yang,Hong-Bin Xu,Zheng Peng,Qian Chen,Yan Li
摘要
Background Pseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient-derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) in this model. Methods Human PMP sample was collected to establish subcutaneous (s.c.) and i.p. Model In vivo study of i.p. injection of 5-FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity. Results Both s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal-pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA-S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5-FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%). Conclusions PDX model of PMCA-S was established successfully, and i.p. 5-FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect.
科研通智能强力驱动
Strongly Powered by AbleSci AI