Suppression of ascites formation and re-accumulation associated with human ovarian cancer by an anti-VPF monoclonal antibody in vivo.
Ascites formation is often observed in ovarian cancer patients. Vascular permeability factor (VPF) may induce ascites formation. We established an animal model of ascites formation and re-accumulation by i.p. transplantation of a human ovarian adenocarcinoma cell line, NOS2, into nude mice. The formation of ascites was observed after 10 days of tumor inoculation and continued for up to 4 weeks. In the ascitic fluid, biologically active VPF was detected. The repeated i.p. administration of an immunoneutralizing monoclonal antibody (MAb) to VPF, MV833, significantly inhibited the formation of ascites throughout the experiments. Re-accumulation of ascites occurred quickly in control mice after aspiration of ascites and these mice died within 20 days. MV833 again inhibited the re-accumulation of ascites and significantly prolonged the life span of mice without any side effect. These results indicate that VPF plays an important role in the accumulation of ascites induced by ovarian cancer and an anti-VPF MAb is a new specific drug to suppress the formation and re-accumulation of ascites. This MAb may contribute to ameliorating quality of life of cancer patients as well as prolong their survival.
Yukita
A
A
Bioscience Research Department, Tsukuba Research Laboratory, Toagosei Co. Ltd., Ibaraki, Japan.
Asano
M
M
Okamoto
T
T
Mizutani
S
S
Suzuki
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001201:Ascites / Q000503:physiopathology / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects*; D002945:Cisplatin / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006470:Hemorrhage / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D012008:Recurrence; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002945:Cisplatin