Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice

Masaru Kimata, Yoshihide Otani, Tetsuro Kubota, Naoki Igarashi, Takeyoshi Yokoyama, Norihito Wada, Nobunari Yoshimizu, Masato Fujii, Kaori Kameyama, Yasunori Okada, Koichiro Kumai, Masaki Kitajima

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21 Citations (Scopus)

Abstract

Marimastat, a matrix metalloproteinese inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. Even with novel approaches such as molecular targeting of cancer chemotherapy, peritoneal dissemination of gastric cancer has little sensitivity to anticancer drugs, and it is impossible to inhibit its growth completely. Intraperitoneal injection of TMK-1 into nude mice at 5 × 105 cells/body resulted in carcinomatous peritonitis that mimicked clinical cases. Continuous administration of marimastat (18 mg/kg/day) from 24 h after the tumor inoculation successfully inhibited the growth of peritoneal dissemination nodules. Combined administration of marimastat (18 mg/kg/day) and mitomycin C (MMC, 2 mg/kg) showed synergistic inhibition of growth of peritoneal dissemination, being superior to MMC alone (2 mg/kg). Although marimastat alone could not increase survival time with statistical significance, combined administration of marimastat and MMC had a survival benefit with statistical significance. The combination of marimastat and MMC increased the preventive effect on peritoneal dissemination. Marimastat seems to be a candidate for the prevention of peritoneal spread of gastric carcinoma.

Original languageEnglish
Pages (from-to)834-841
Number of pages8
JournalJapanese Journal of Cancer Research
Volume93
Issue number7
Publication statusPublished - 2002

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Keywords

  • Gastric cancer
  • Marimastat
  • MMP inhibitor
  • Peritoneal dissemination

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kimata, M., Otani, Y., Kubota, T., Igarashi, N., Yokoyama, T., Wada, N., Yoshimizu, N., Fujii, M., Kameyama, K., Okada, Y., Kumai, K., & Kitajima, M. (2002). Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice. Japanese Journal of Cancer Research, 93(7), 834-841.