Induction of tumor necrosis factor in a murine tumor by systemic administration of a novel synthetic lipid A analogue, ONO-4007.
The effect of a novel synthetic lipid A analogue, ONO-4007, on tumor necrosis factor (TNF) production was investigated in normal and tumor-bearing mice. When vehicle was administered to normal mice, slight TNF activity was detected in some organs, but more TNF activity was detected in spleen, liver, lung, kidney, and serum when ONO-4007 (300 micrograms/mouse) was administered. When vehicle was given to tumor bearers, on the other hand, little TNF was detected in most organs, but when ONO-4007 was given, more TNF was produced in many organs, particularly spleen, liver, and tumor tissue. TNF production of spleen and liver reached a maximum 1-2 h after ONO-4007 injection and then decreased rapidly, but that of tumor remained high for at least 6 h after administration. When mice were pretreated with dexamethasone, TNF activity of normal organs were completely inhibited, but that of tumor was only partially decreased. We have shown that ONO-4007 causes rapid, definite growth inhibition of solid tumor, and speculate that long-sustained intratumoral TNF is the main cause of this beneficial anti-tumor effect. We report here that ONO-4007 can induce TNF in tumor locus, and its utilization may offer a new therapeutic method.
Ueda
H
H
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Yamazaki
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005938:Glucocorticoids / Q000494:pharmacology; D007275:Injections, Intravenous; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D008050:Lipid A; C086889:ONO 4007; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone