Angiogenesis inhibitor TNP-470 augments the effect of repeated arterial ischemia on growth but does not affect take in a rat liver tumor model.
Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes place from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP-470 decreases the risk of tumor take in the liver after intraportal injection of viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP-470 gave a smaller increase in tumor volume than transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retardation of tumor growth (p < 0.01 as compared to controls) but did not affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor.
Möller
P H
PH
Department of Surgery, University of Lund, University Hospital, Sweden.
Ivarsson
K
K
Roos
G
G
Radnell
M
M
Persson
B
B
Tranberg
K G
KG
Stenram
U
U
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003510:Cyclohexanes; D007511:Ischemia; D008099:Liver / Q000098:blood supply; D008113:Liver Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol