Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice.
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.
Kimata
Masaru
M
Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
Otani
Yoshihide
Y
Kubota
Tetsuro
T
Igarashi
Naoki
N
Yokoyama
Takeyoshi
T
Wada
Norihito
N
Yoshimizu
Nobunari
N
Fujii
Masato
M
Kameyama
Kaori
K
Okada
Yasunori
Y
Kumai
Koichiro
K
Kitajima
Masaki
M
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
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