The effect of an angiogenesis inhibitor (FR-118487) on rat experimental hepatoma -Immunohistological analysis-

点击翻译按钮获取中文摘要

The effect of FR-118487 (FR) as an angiogenesis inhibitor was examined immunohistologically with rat DEN experimental hepatoma. Supposing its clinical application, FR was administered by four routes. In addition, its combined effects with PEIT for local use and with Epi.ADR for arterial use were examined. Taking multicentric occurrence into consideration, chemoprevention of FR was examined. In systemic administration of FR group, no distinct nodal lesion and no cancer lesions were found at Week 12 (DEN hepatoma period), suggesting its chemoprevention. Serum AFP levels in FR group were distinctly lower than those in FR untreated group. As for the effect of FR after carcinogenesis, the percent of cancer area was lower than FR untreated group. After local and intra-arterial administration, the suppressed growth of lesion was evident with a reducing effect. Serum AST,ALT,AFP also reflected its efficacy. Laminin and PCNA were suppressed to appear in the tumor growth suppressed or reduced site, suggesting an important role of laminin expression during carcinogenesis. In consideration of the fact that hepatic sinusoidal endothelial cells (HSEC) produce laminin during carcinogenesis, FR was suggested to act not only on the blood vessel surrounding the tumor but also on HSEC.The expression ofGST-P was also suppressed during carcinogenesis. Body weight loss was criticized in the systemically treated group but no significant difference was found in the local and arterial injection. It was interesting that remaing viable cells, infiltrated lymphocytes, and fibrosis were decreased in surroundings of tumor in the case of FR combined with PEIT.From the evidences mentioned above, FR,administered singly or combined with PEIT or chemotherapy, seems to be a new ideal remedy for treatment of hepatoma. In relation to this series, other vascularization-related factors such as IL-12, IFN-gamma, IP-10, and IGIF are now under investigation, including clinical cases.