Prevention of Peritoneal Carcinomatosis from Colon Cancer Cell Seeding Using a Pirarubicin Solution in Rats and Nude Mice

Abstract

Free malignant cells, which are frequently detected in the washing liquid from the peritoneal cavity before and after resection of human colorectal cancer, are suspected to cause recurrent peritoneal cancer. We carried out an experimental study to compare the prophylactic efficacy of washing the peritoneum with several anticancer drugs and the antiseptic povidone-iodine against the development of peritoneal carcinomatosis from colonic origin in rats and nude mice. The in vitro anticancer activity of a short, 15-minute exposure of pirarubicin, doxorubicin, 5-fluorouracil, cisplatin, mitomycin C, and 1% povidone-iodine was first evaluated by an MTT assay on DHD/K12/PROb rat and LS174T human colon cancer cells. For the in vivo experiments, BDIX rats were inoculated intraperitoneally (i.p.) with 1 x 10(6) DHD/K12/PROb cells followed by peritoneal scarring and a colocolic anastomosis. A 15-minute peritoneal washing with the anticancer drugs or povidone-iodine was then performed. Nude mice were i.p.-inoculated with 1 x 10(7) LS174T human cells and treated 2 hours later with i.p. pirarubicin. Only pirarubicin, mitomycin C, and povidone-iodine were fully cytotoxic in vitro against DHD/K12/PROb rat colon cancer cells. In contrast to pirarubicin and povidone-iodine, mitomycin C was not completely active against LS174Tcells. In vivo, pirarubicin cured DHD/K12/PROb-inoculated rats, even at the site of the peritoneal scarring and intestinal anastomosis. i.p. pirarubicin prevented the development of peritoneal carcinomatosis and liver metastasis in LS174T-inoculated mice. i.p. washing with pirarubicin cured 2-day-old, but not 7-day-old, peritoneal carcinomatosis in rats. Short exposure to i.p. pirarubicin is nontoxic and more active than povidone-iodine and other anticancer drugs in preventing the development of peritoneal carcinomatosis from colonic origin in rats and mice. The prophylactic effect of preoperative peritoneal washing with pirarubicin on the development of recurrent peritoneal cancer should be evaluated in a randomized clinical trial.

Pilot Study of Transarterial Chemoembolization With Pirarubicin and Amiodarone for Unresectable Hepatocellular Carcinoma

“…29,30 In a previous study, the prolonged stability of a lipiodol emulsion with anthracycline was reported when an iv formulation for amiodarone was added to the anthracycline-lipiodol mixture. 20 Knowing that amiodarone is an inhibitor of the multidrug resistance phenotype, and that pirarubicin is a more active anthracycline than classic doxorubicin for experimental local anticancer treatment, 31 we took the decision 7 years ago to modify our routine TACE procedure by using pirarubicin and amiodarone, when possible. This study retrospectively assesses this modified TACE procedure in a small pilot cohort of 43 patients.…”

An in vivo rat model for early development of colorectal cancer metastasis to liver

“…(1983), further work has shown that DHDK12 colonic cancer produces macroscopic metastases in immunocompetent BDIX rats (Benoit et al. 2000, 2006; Favoulet et al. 2002, 2004; Mezhir et al.…”

“…1983). Many models studying later stages of metastasis development have used this biologically accurate cancer cell line–host combination (Favoulet et al. 2004; Kobaek‐Larsen et al.…”

“…Extensive work has focused on the influence of cancer cell line-host selection in macroscopic metastasis models. As the initial work by Martin et al (1983), further work has shown that DHDK12 colonic cancer produces macroscopic metastases in immunocompetent BDIX rats (Benoit et al 2000(Benoit et al , 2006Favoulet et al 2002Favoulet et al , 2004Mezhir et al 2006). Human colorectal cancer liver metastasis development in immunocompetent mice showed considerable variation with regard to tumour propagation and dissemination.…”

“…DHDK12 is a chemically induced rat colon carcinoma cell line induced from BDIX rats (Martin et al 1983). Many models studying later stages of metastasis development have used this biologically accurate cancer cell line-host combination (Favoulet et al 2004;Kobaek-Larsen et al 2004;Sinibaldi et al 2004;Benoit et al 2006;Mezhir et al 2006). Using Calcein acetoxymethylester (Calcein AM) as an intracellular label and an intra-arterial method of tumour cell introduction, we compared early liver metastasis development in the four experimental groups -DHDK12 in BDIX, DHDK12 in SD, HT29 in SD and HT29 in BDIX.…”