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

血管生成抑制剂（FR-118487）对大鼠实验性肝癌的作用-免疫组织学分析-

基本信息

批准号：
07671429
负责人：
ISHII Yuji
金额：
$ 1.22万
依托单位：
JIKEI UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

通过大鼠 DEN 实验性肝癌的免疫组织学检查 FR-118487 (FR) 作为血管生成抑制剂的作用。假设其临床应用，FR有四种给药途径。此外，还检查了其与局部使用的 PEIT 和动脉使用的 Epi.ADR 的联合效果。考虑到多中心发生，研究了 FR 的化学预防。 FR组全身给药第12周（DEN肝癌期）未发现明显的淋巴结病变，也未发现癌性病变，提示其具有化学预防作用。 FR组血清AFP水平明显低于FR未治疗组。至于癌变后FR的效果，癌症面积的百分比低于FR未治疗组。局部和动脉注射后，对病灶生长的抑制作用明显，具有减轻作用。血清AST、ALT、AFP也反映其疗效。层粘连蛋白和PCNA在肿瘤生长抑制或减少的部位被抑制出现，表明层粘连蛋白表达在癌发生过程中发挥重要作用。考虑到肝窦内皮细胞(HSEC)在癌变过程中产生层粘连蛋白，因此认为FR不仅作用于肿瘤周围的血管，而且还作用于HSEC。癌变过程中GST-P的表达也受到抑制。全身治疗组的体重减轻受到批评，但局部注射和动脉注射没有发现显着差异。有趣的是，FR联合PEIT时，肿瘤周围残留的活细胞、浸润的淋巴细胞和纤维化均减少。从上述证据来看，FR单独给药或与PEIT或化疗联合给药，似乎是一种新的治疗方法。治疗肝癌的理想药物。与该系列相关的其他血管形成相关因素，如 IL-12、IFN-γ、IP-10 和 IGIF，包括临床病例，目前正在研究中。