title: DT-5461a, an antitumor synthetic lipid a analog, causes selective blood flow reduction in tumor tissue.
abstract: We previously reported that a synthetic low-toxicity lipid A analog, DT-5461a, exhibited a significant antitumor effect was characteristically accompanied by extensive tumor necrosis, suggesting that DT-5461a causes a local circulatory disturbance in tumor tissues. In this study, we investigated the effect of DT-5461a on regional blood flow in various organs including tumor tissue with a radiolabeled tracer-distribution technique using 14C-iodoantipyrine. Intravenous administration of DT-5461a induced blood flow reduction in Meth A tumor subcutaneously implanted into BALB/c mice, but not in liver, spleen or lung of these mice. This tumor tissue-specific reduction in blood flow was significantly inhibited by pretreatment with antisera against tumor necrosis factor (TNF) alpha, interferon (IFN) alpha/beta, and IFN gamma. These results indicate that endogenously induced cytokines, namely TNF alpha and IFNs, are involved in the intratumor blood flow reduction caused by DT-5461a.
authors.affiliation: Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Akimoto
authors.forename: E
authors.initials: E
authors.lastname: Kumazawa
authors.forename: T
authors.initials: T
authors.lastname: Jimbo
authors.forename: N
authors.initials: N
authors.lastname: Joto
authors.forename: A
authors.initials: A
authors.lastname: Tohgo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000098:blood supply*; D007106:Immune Sera / Q000494:pharmacology; D007372:Interferons / Q000037:antagonists & inhibitors / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012039:Regional Blood Flow / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D004187:Disaccharides; D007106:Immune Sera; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; C077208:DT 5461; D007372:Interferons