Efficacy of intraperitoneal chemotherapy with paclitaxel targeting peritoneal micrometastasis as revealed by GFP-tagged human gastric cancer cell lines in nude mice.

Abstract

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.

• Authors: Norifumi Ohashi, Yasuhiro Kodera, Hayao Nakanishi, Hiroyuki Yokoyama, Michitaka Fujiwara, Masahiko Koike, Kenji Hibi, Akimasa Nakao, Masae Tatematsu
• Journal: International journal of oncology (Int J Oncol) Vol. 27 Issue 3 Pg. 637-44 (Sep 2005) ISSN: 1019-6439 [Print] Greece
• PMID: 16077911 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Platelet Endothelial Cell Adhesion Molecule-1
• Green Fluorescent Proteins
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Line, Tumor
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Immunohistochemistry
• Injections, Intraperitoneal
• Injections, Intravenous
• Male
• Mice
• Mice, Nude
• Neovascularization, Pathologic (metabolism, pathology)
• Paclitaxel (administration & dosage, pharmacokinetics, therapeutic use)
• Peritoneal Neoplasms (drug therapy, mortality, secondary)
• Plasmids (genetics)
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis)
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Survival Analysis
• Survival Rate
• Transfection
• Treatment Outcome
• Xenograft Model Antitumor Assays (methods)