The development of novel treatment through the hepatocellular carcinoma (HCC) specific siginaling pathway and molecular based gene expression profiling for advanced HCC

通过肝细胞癌 (HCC) 特异性信号通路和基于分子的基因表达谱治疗晚期 HCC 的新型治疗方法的开发

• 批准号: 17390367
• 负责人: UMESHITA Koji
• 金额: $ 9.47万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390367/
• 关键词: hepatocellular carcinoma; advanced cancer; portal venous thrombus; IFN-α; chemotherapy; IFN-receptor; angiogenesis; Gene Expression Profiling; IFN併用化学療法; TRAIL; NK細胞; Fas; Fas-L; Angiopoietin; 難治性進行癌

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. In this mechanism, the methylation of IFNAR gene was significantly correlated with anti-tumor effect, among the several factors.2) Anti tumor effect through the relationship between IFN and 5FU metabolismIn the anti-tumor effect of IFN and 5FU, IFN would induce the TS-1 inhibitory rate in 5FU metabolism.3) Anti tumor effect through Fas/FasLAmong peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of CTL system in the anti tumor effect was examined and confirmed in terms of the relationship of apoptosis in this study.4) Anti tumor effect through the anti-angiogenic actionAbout the anti-angiogenic action of IFN, Ang-2 was the one of most important factor, among several anti-angiogenic molecules, TSP, Ang-1, VEGF, Tie2, HIF1-α.5) 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)通过IFN-IFNAR信号通路的抗肿瘤作用机制IFN/5-FU联合治疗肝癌细胞体外抗肿瘤效果与IFNAR表达强度显著相关。在这一机制中，IFNAR基因的甲基化与抗肿瘤作用显著相关。2)通过IFN与5FU代谢关系的抗肿瘤作用IFN与5FU的抗肿瘤作用中，IFN会诱导TS-1抑制5FU代谢。3)通过Fas/ fasl的抗肿瘤作用在外周血中发现NK细胞对人肝癌细胞具有细胞毒作用。此外，本研究还从细胞凋亡的关系方面考察并证实了CTL系统参与抗肿瘤作用。在IFN的抗血管生成作用中，在TSP、Ang-1、VEGF、Tie2、HIF1-α等几种抗血管生成分子中，Ang-2是最重要的因子之一。5)基因表达谱应用IFN-α和5- fu治疗的临床样本，基因表达谱预测治疗效果的准确率在85%以上。

项目成果

Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.

• DOI: 10.3892/ijo.26.2.319
• 发表时间: 2005-02
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: B. Damdinsuren;H. Nagano;M. Kondo;Hirofumi Yamamoto;N. Hiraoka;Tameyoshi Yamamoto;S. Marubashi;A. Miyamoto;K. Umeshita;K. Dono;S. Nakamori;K. Wakasa;M. Sakon;M. Monden

Clinical and pathological features of Allen's type C classification of resected combined hepatocellular and cholangiocarcinoma : a comparative study with hepatocellular carcinoma and cholangiocellular carcinom.

切除的混合型肝细胞癌和胆管细胞癌的 Allen C 型分类的临床和病理特征：肝细胞癌和胆管细胞癌的比较研究。

• 发表时间: 2006
• 期刊: J Gastronitest Surg 2006 10(7)
• 作者: Tang D.;Nagano H.;Nakamura M.;Wada H.;Marubashi S.;Miyamoto A.;Takeda Y.;Umeshita K.;Dono K.;Monden M.
• 通讯作者: Monden M.

TGF-betal-induced cell growth arrest and partial differentiation is related to the suppression of Idl in human hepatoma cells.

TGF-β诱导的细胞生长停滞和部分分化与人肝癌细胞中Idl的抑制有关。

• 发表时间: 2006
• 期刊: Oncol Rep 15(2)
• 作者: Damdinsuren B.;Nagano H.;Kondo M.;Natsag J.;Hanada H.;Nakamura M.;Wada H.;Kato H.;Marubashi S.;Miyamoto A.;Takeda Y.;Umeshita K.;Dono K.;Monden M.
• 通讯作者: Monden M.

進行肝癌に対するインターフェロン併用化学療法と外科治療

化疗联合干扰素及手术治疗晚期肝癌

• 发表时间: 2005
• 期刊: 消化器科 40(6)
• 作者: 永野浩昭;門田守人
• 通讯作者: 門田守人

特集 肝臓におけるゲノミクス研究 6.肝細胞癌・化学療法感受性予測-IFN/5FU併用療法の効果予測-

专题 肝脏基因组学研究 6. 肝细胞癌/化疗敏感性预测 - IFN/5FU联合治疗效果预测 -

• 发表时间: 2005
• 期刊: 肝臓 46(10)
• 作者: 黒川幸典;永野浩昭;門田守人
• 通讯作者: 門田守人