Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats

Japanese Journal of Cancer Research : Gann
T IkebeM Sakurai

Abstract

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 su...Continue Reading

References

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Citations

Nov 4, 2000·Expert Opinion on Investigational Drugs·E A Kruger, W D Figg
Nov 3, 2004·Journal of Hepatology·David Semela, Jean-François Dufour
Mar 28, 2006·Cancer Letters·Roberta Pang, Ronnie T P Poon
May 18, 2000·Cancer Treatment Reviews·M M EatockS B Kaye
Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y Q WangK Kaneda

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