Efficacy of intraperitoneal chemotherapy with paclitaxel targeting peritoneal micrometastasis as revealed by GFP-tagged human gastric cancer cell lines in nude mice.
To explore the effect of chemotherapy against peritoneal micrometastases, we used in vivo models of peritoneal micrometastasis featuring three human gastric cancer cell lines tagged with the green fluorescence protein gene. With a highly metastatic cell line, GCIY-EGFP, the survival rate of mice treated with weekly intraperitoneal paclitaxel starting one day following inoculation was significantly higher than those of control mice or mice given the same treatment starting on day eight. Intravenous paclitaxel exhibited no significant survival benefit regardless of the treatment schedule. Pharmacokinetic analysis revealed that the concentration of paclitaxel in the metastatic nodules treated with intraperitoneal administration was 2-3-fold higher than those treated with intravenous paclitaxel, provided the treatment was given on day one. Even greater responses were observed with less aggressive MKN28-EGFP and MKN45-EGFP cell lines, whose peritoneal metastases resolved completely due to early intraperitoneal treatment in 13 of the 14 mice tested. These results indicate that intraperitoneal paclitaxel is effective against peritoneal metastasis in early phase.
Ohashi
Norifumi
N
Department of Surgery II, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kodera
Yasuhiro
Y
Nakanishi
Hayao
H
Yokoyama
Hiroyuki
H
Fujiwara
Michitaka
M
Koike
Masahiko
M
Hibi
Kenji
K
Nakao
Akimasa
A
Tatematsu
Masae
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D010957:Plasmids / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate; D014162:Transfection; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D017239:Paclitaxel