Establishment of patient-derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil.
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.
['Lin|Yu-Lin|YL|', 'Zhang|Jue|J|', 'Yan|Feng-Cai|FC|', 'Jiang|Xi|X|', 'Ma|Ru|R|', 'Yang|Zhi-Ran|ZR|', 'Xu|Hong-Bin|HB|', 'Peng|Zheng|Z|', 'Chen|Qian|Q|', 'Li|Yan|Y|0000-0001-6018-6538']
D000818:Animals D018279:Carcinoma, Signet Ring Cell D005260:Female D005472:Fluorouracil D006801:Humans D007274:Injections, Intraperitoneal D008297:Male D051379:Mice D008875:Middle Aged D010534:Peritoneal Neoplasms D011553:Pseudomyxoma Peritonei D023041:Xenograft Model Antitumor Assays
intraperitoneal injection pseudomyxoma peritonei 5-FU PDX model organ toxicity