title: Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice.
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 x 10( 5) 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.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kimata
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Otani
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kubota
authors.forename: Naoki
authors.initials: N
authors.lastname: Igarashi
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Norihito
authors.initials: N
authors.lastname: Wada
authors.forename: Nobunari
authors.initials: N
authors.lastname: Yoshimizu
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kumai
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use; D008956:Models, Chemical; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010537:Peritoneum / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology* / Q000628:therapy; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D016685:Mitomycin; C100342:marimastat; C022616:thiazolyl blue