The establishment of immuno-chemotherapy through the IFN-IFNAR (IFN-α receptor) signaling pathway for the intractable and advanced hepatocellular carcinoma

通过IFN-IFNAR（IFN-α受体）信号通路建立针对难治性晚期肝细胞癌的免疫化疗

• 批准号: 15390396
• 负责人: MARUBASHI Shigeru
• 金额: $ 7.74万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390396/
• 关键词: hepatocellular carcinoma; IFN-α; IFN-receptor; TRAIL; NK cell; Fas-FasL; Gene Expression Profiling; 門脈内腫瘍栓; IFN併用化学療法; IFN受容; STAT-phosphoSTAT; IFN; IFNAR; 5-FU; 免疫組織染色

1)The mechanism of the antitumor effect through the IFN-IFNAR signalingThe anti-tumor effect of IFN/5-FU combined therapy was significantly correlated with the strength of IFNAR expression, in the HCC cells in-vitro. This was also proved in the experiment of the IFNAR gene transfection model. In this mechanism, the upragulation of the p-STATS and Bcl-xl expression were most significantly correlated with anti-tumor effect, among the several signal transductional factors.2)Anti tumor effect through TRAIL/TRAIL receptor and Fas/FasLIFN-α and 5-FU enhanced TRAIL expression in peripheral mononuclear cells, and TRAIL receptor in cultured hepatoma cells. Among peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of Fas/FasL system in the anti tumor effect was examined and confirmed in this study. The indirect anti-tumor effect for HCC cells through Fas/FasL system was mediated by the Caspase and FLIP.3)The Gene Expression ProfilingUsing the clinical samples treated by IFN-α and 5-FU, the gene expression profiling would be suggested to be useful for the prediction of the treatment efficacy at the over 85%.

1)IFN/5-FU联合治疗肝癌细胞的抗肿瘤作用与IFN-α R的表达强度密切相关。在IFNAR基因转染模型的实验中也证明了这一点。2）TRAIL/TRAIL受体、Fas/FasLIFN-α和5-FU通过增强外周血单个核细胞中TRAIL的表达和肝癌细胞中TRAIL受体的表达而发挥抗肿瘤作用。在外周血细胞中，发现NK细胞对人肝癌细胞具有细胞毒作用。此外，本研究还证实了Fas/FasL系统参与了抗肿瘤作用。Caspase和FLIP介导Fas/FasL系统对肝癌细胞的间接抗肿瘤作用。3）基因表达谱分析以IFN-α和5-FU联合治疗的临床标本为例，基因表达谱分析可用于85%以上的疗效预测。

项目成果

Expression of Id proteins in human hepatocellular carcinoma : Relevance to tumor dedifferntiation

Id蛋白在人肝细胞癌中的表达：与肿瘤去分化的相关性

• 发表时间: 2005
• 期刊: Int J Oncol 26
• 作者: Bazarragchaa D.;Marubashi S;et al.
• 通讯作者: et al.

Expression of Id proteins in human hepatocellular carcinoma : Relevance to tumor dedifferntiation.

Id 蛋白在人肝细胞癌中的表达：与肿瘤去分化的相关性。

• 发表时间: 2005
• 期刊: Int J Oncol 26
• 作者: Bazarragchaa D.;Nagano H.et al.
• 通讯作者: Nagano H.et al.

進行肝細胞癌の治療-予後の改善を考えて

晚期肝细胞癌的治疗——考虑改善预后

• 发表时间: 2004
• 期刊: 医学と薬学 52(5)
• 作者: 宮本敦史;丸橋繁;他
• 通讯作者: 他

Akt2 expression correlates with prognosis of human hepatocellular carcinoma.

• DOI: 10.3892/or.11.1.25
• 发表时间: 2004
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Xundi Xu;M. Sakon;H. Nagano;N. Hiraoka;Hirofumi Yamamoto;N. Hayashi;K. Dono;S. Nakamori;K. Umeshita

Damdinsuren B., Nagano H.et al.: "Interferon-beta is more potent than interferon-alpha in inhibition of human hepatocellular carcinoma cell growth when used alone and in combination with anticancer drugs."Ann Surg Oncol. 10(10). 1184-1190 (2003)

Damdinsuren B.、Nagano H.等人：“单独使用或与抗癌药物联合使用时，干扰素 β 比干扰素 α 更能有效抑制人肝细胞癌细胞的生长。”Ann Surg Oncol。