Development of novel therapy for hepatocellular carcinoma targeting of bone marrow-derived angiogenesis precursor

以骨髓源性血管生成前体为靶点的肝细胞癌新疗法的开发

• 批准号: 22590729
• 负责人: KANTO Tatsuya
• 金额: $ 2.83万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590729/
• 关键词: 肝癌; 血管新生; TIE2; 骨髄系前駆細胞

Angiogenesis is a critical step in the development of vascular-rich hepatocellular carcinoma (HCC). TIE-2, a receptor of angiopoietins, conveys pro-angiogenic signals. We thus aimed to clarify the roles of TIE2-expressing monocytes (TEMs) in the clinical management of HCC and to identify molecules involving in the differentiation of TEMs. In HCC patients, the frequency of TEMs in the periphery and in the liver was significantly higher than those in non-HCC groups. In patients who underwent local ablation of HCC, the frequency of TEMs changed in parallel with the recurrence of HCC. A significant positive correlation was observed between micro-vessel density in HCC tissues and the frequencies of TEMs, suggesting that TEMs are involved in angiogenesis in the liver. Receiver operating characteristic analyses revealed the superiority of TEM frequency to AFP, PIVKA-II and ANG-2 levels as a diagnostic for HCC. TEMs were generated from TIE2-negative monocytes in the presence of M-CSF, TNF-α and IL-1β. In conclusion, the frequency of TEMs can be used as a diagnostic marker for HCC, potentially reflecting angiogenesis in the liver.

血管生成是富血管肝细胞癌（HCC）发展的关键步骤。TIE-2是一种血管生成素受体，传递促血管生成信号。因此，我们旨在阐明表达tie2的单核细胞（TEMs）在HCC临床管理中的作用，并确定参与TEMs分化的分子。在HCC患者中，外周和肝脏中tem的频率明显高于非HCC组。在肝细胞癌局部消融的患者中，tem的频率与肝细胞癌的复发同步变化。肝细胞癌组织微血管密度与tem频率呈显著正相关，提示tem参与肝脏血管生成。受者工作特征分析显示TEM频率比AFP、PIVKA-II和ANG-2水平在HCC诊断中的优势。在M-CSF、TNF-α和IL-1β存在下，由tie2阴性单核细胞生成tem。总之，tem的频率可以作为HCC的诊断指标，可能反映肝脏血管生成。

项目成果

Type-I and type-III interferon induction from myeloid and plasmacytoid dendritic cells in chronic hepatitis C patients ; lack of association with single nucleotide polymorphism near IL28B gene

慢性丙型肝炎患者的髓系和浆细胞样树突状细胞诱导 I 型和 III 型干扰素；

• 发表时间: 2010
• 作者: Miyazaki M;Kanto T;et al.
• 通讯作者: et al.

Pro-angiogenic receptor TIE2-expressing monocytes/TEMs as novel diagnostic marker for HCV-infected hepatocellular carcinoma

表达促血管生成受体 TIE2 的单核细胞/TEM 作为 HCV 感染的肝细胞癌的新型诊断标志物

• 发表时间: 2010
• 作者: Matsubara M;Kanto T;et al.
• 通讯作者: et al.

大阪大学大学院医学系研究科消化器内科学ホームページ

大阪大学大学院医学研究科消化内科主页

Enhanced ability of IL28A and IL28B induction in plasmacytoid dendritic cells in chronic hepatitis C patients with major allele of IL28B single nucleotide polymorphism.

具有 IL28B 单核苷酸多态性主要等位基因的慢性丙型肝炎患者浆细胞样树突状细胞中 IL28A 和 IL28B 诱导能力增强。

• 发表时间: 2011
• 作者: Kakita N;Kanto T;Miyazaki M;Yoshio S;Kuroda S;Matsubara T;Higashitani K;Sakakibara M;Hiramatsu N;Kasahara A;Takehara T;Hayashi N
• 通讯作者: Hayashi N

Enhanced ability of IL28A and IL28B induction in plasmacytoid dendritic cells in chronic hepatitis C patients with major allele of IL28B single nucleotide polymorphism

具有IL28B单核苷酸多态性主要等位基因的慢性丙型肝炎患者浆细胞样树突状细胞中IL28A和IL28B诱导能力增强

• 发表时间: 2011
• 作者: Kakita N;Kanto T;et al
• 通讯作者: et al