TY - JOUR
T1 - Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice
AU - Kimata, Masaru
AU - Otani, Yoshihide
AU - Kubota, Tetsuro
AU - Igarashi, Naoki
AU - Yokoyama, Takeyoshi
AU - Wada, Norihito
AU - Yoshimizu, Nobunari
AU - Fujii, Masato
AU - Kameyama, Kaori
AU - Okada, Yasunori
AU - Kumai, Koichiro
AU - Kitajima, Masaki
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - MMP inhibitor
KW - Marimastat
KW - Peritoneal dissemination
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U2 - 10.1111/j.1349-7006.2002.tb01326.x
DO - 10.1111/j.1349-7006.2002.tb01326.x
M3 - Article
C2 - 12149150
AN - SCOPUS:0036048505
SN - 0910-5050
VL - 93
SP - 834
EP - 841
JO - Japanese Journal of Cancer Research
JF - Japanese Journal of Cancer Research
IS - 7
ER -
