Experimental Study
Experimental study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil to treat PDX model of pseudomyxoma peritonei
Lin Yulin, Zhang Jue, Yan Fengcai, Jiang Xi, Ma Ru, Yang Zhiran, Li Yan
Published 2019-10-08
Cite as Chin J Exp Surg, 2019,36(10): 1798-1801. DOI: 10.3760/cma.j.issn.1001-9030.2019.10.020
Abstract
ObjectiveTo evaluate the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil (5-Fu) in patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP).
MethodsOne 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.
ResultsPDX 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.
ConclusionIn 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.
Key words:
Pseudomyxoma peritonei; PDX model; 5-Fluorouracil; Intraperitoneal injection; Organ toxicity
Contributor Information
Lin Yulin
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Zhang Jue
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Yan Fengcai
Department of Pathology, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Jiang Xi
Department of Pathology, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Ma Ru
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Yang Zhiran
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China
Li Yan
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital affiliated to Capital Medical University, Beijing 100038, China