Effect of FR143430, a novel cytokine suppressive agent, on adenocarcinoma colon26-induced cachexia in mice.
Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. In this study the effect of FR143430, (2-(4-fluorophenyl)-4, 5, 6, 7-tetrahydro-3-(4-pyridyl)pyrazolo[1, 5-a]pyrimidine monohydrochloride), an inhibitor of Interleukin-1 and Tumor necrosis factor-a (TNF- a), on adenocarcinoma colon26-induced cachexia was investigated in mice. Tumor growth was not affected. Nevertheless, treatment with FR143430 (0.1 to lmg) into the tumor resulted in the attenuation of the reduction in body weight, food intake, epididymal fat and carcass weight, the decrease in the circulating levels of triglyceride and glucose, and the increase in the circulating levels of total cholesterol, non esterified free fatty acid (NEFA) and total protein, which were induced by the presence of the tumor. However, oral treatment with FR143430 failed to show an inhibitory effect on cachexia induction. Overall, this study demonstrated that the cachexia induced by colon26 was alleviated by the injection of FR143430 into the tumor in sufficient quantity, without any effect on tumor growth, suggesting the potential utility of cytokine suppressive agents e for the treatment of cancer cachexia.
Yamamoto
N
N
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Kawamura
I
I
Nishigaki
F
F
Tsujimoto
S
S
Naoe
Y
Y
Inami
M
M
Elizabeth
L
L
Manda
T
T
Shimomura
K
K
D000818:Animals; D002100:Cachexia / Q000097:blood / Q000188:drug therapy*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
D016207:Cytokines; C111838:FR 143430; D011720:Pyrazoles; D011743:Pyrimidines