Intratumoral tumor necrosis factor induction and tumor growth suppression by ONO-4007, a low-toxicity lipid A analog.

Abstract

BACKGROUND:

ONO-4007 is a lipid A analog with low toxicity.

MATERIALS AND METHODS:

The antitumor activity and tumor necrosis factor (TNF)-inducing activity of ONO-4007 were compared with those of lipopolysaccharide (LPS) in WKAH rats bearing KDH-8 hepatoma cells.

RESULTS:

Weekly injections of ONO-4007 (3 and 10 mg/kg i.v.) suppressed tumor growth, but LPS (0.01 and 0.1 mg/kg i.v.) did not. A single injection of ONO-4007 (3 and 10 mg/kg i.v.) into tumor-bearing rats induced higher levels of endogenous TNF production in tumor tissues than LPS (0.001, 0.01 and 0.1 mg/kg i.v.). Repeated injections of LPS caused a reduction of TNF production in tumor tissues, whereas the reduction by ONO-4007 was less remarkable than that by LPS. Intratumoral injections of anti-rat TNF-alpha antibody attenuated the antitumor effect of ONO-4007.

CONCLUSION:

The antitumor effect of ONO-4007 is more pronounced than that of LPS and the effect is mediated by TNF produced in tumor tissues.

• Authors: N Matsumoto, H Oida, Y Aze, A Akimoto, T Fujita
• Journal: Anticancer research (Anticancer Res) 1998 Nov-Dec Vol. 18 Issue 6A Pg. 4283-9 ISSN: 0250-7005 [Print] Greece
• PMID: 9891479 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Antineoplastic Agents
• Lipid A
• Lipopolysaccharides
• ONO 4007
• Tumor Necrosis Factor-alpha
• Diclofenac
• Indomethacin

Topics

• Animals
• Antibodies
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Cell Division (drug effects)
• Diclofenac (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Indomethacin (pharmacology)
• Injections, Intravenous
• Lipid A (administration & dosage, analogs & derivatives, therapeutic use)
• Lipopolysaccharides (administration & dosage, toxicity)
• Liver (drug effects, immunology)
• Liver Neoplasms, Experimental (drug therapy, genetics, immunology, pathology)
• Male
• Rabbits
• Rats
• Rats, Inbred Strains
• Spleen (drug effects, immunology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)