Intra-arterial administration of the angiogenesis inhibitor TNP-470 blocks liver metastasis in a rabbit model.
We evaluated the best route of administration of TNP-470, an angiogenesis inhibitor, by comparing the anti-tumour effects and toxicity following injection via the hepatic artery, the portal vein, or the jugular vein in a rabbit model of liver metastases. Following the injections of 1 x 10(6) VX2 carcinoma cells into the portal vein of rabbits, 50 mg of TNP-470 was injected continuously into the hepatic artery, portal vein, or jugular vein for 7 days. The number of tumours on the surface of the liver was counted 14 days following the start of the infusion, and the serum glutamic-oxaloacetic transamine (GOT), glutamic-pyruvic transaminase (GPT) and total bilirubin concentrations were examined. In addition, a coloured silicon rubber was injected into the vessels of the liver to visualise the capillary networks around the tumours and assess the degree of suppression of angiogenesis by TNP-470. The mean number of tumours following intra-arterial injection (17.5 +/- 2.9) was significantly less than the control (237.0 +/- 34.0) (P < 0.05). The mean numbers of the tumours following intraportal (89.1 +/- 16.0) and intravenous (140.6 +/- 31.2) injection were both less than the controls (215.3 +/- 45.5, 284.8 +/- 55.4 respectively), but the differences were not significant. We conclude that intra-arterial injection of TNP-470 is the most effective method for preventing liver metastases in this model.
Tanaka
H
H
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Taniguchi
H
H
Mugitani
T
T
Koishi
Y
Y
Masuyama
M
M
Higashida
T
T
Koyama
H
H
Suganuma
Y
Y
Miyata
K
K
Takeuchi
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003510:Cyclohexanes; D004195:Disease Models, Animal; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000517:prevention & control* / Q000556:secondary*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011169:Portal Vein; D011817:Rabbits; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol