Basic and clinical studies regarding to the identification of inflammatory factors promoting the malignant transformation mechanism in digestive organ cancer

促进消化器官癌恶变机制的炎症因子鉴定的基础与临床研究

• 批准号: 23591992
• 负责人: UENO Shinichi
• 金额: $ 3.16万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591992/
• 关键词: HCC; TAM; TLR-4; HMGB1; FrB immunotoxin; ZEB-1; RAGE; 悪性化; Fr-Bイムノトキシン; EMT; ZEB1; E-cadherin; RAGE[

To investigate the cancer transformation of human hepatocellular carcinoma (HCC), the change of HMGB1 and its receptor TLR-4 with tissue macrophage (TAM) were analyzed. Moreover, the usefulness of FrB immunotoxin against TAM was studied if it could diminish tumor's malignant transformation. In HCC, correlations of HMGB1 level and number of TAM, and the number of TAM and patients prognosis were seen. For the knowledge about EMT, transcription factor ZEB-1 participated, too. On the other hand, after giving FrB immunotoxin to nude mouse HepG2 transplant model under skin, a clear effect of tumor promotion was seen. With these considerations, it was suggested that HMGB1 and derived TAM would contribute to the malignant transformation of HCCs, and FrB immunotoxin could be a treatment strategy.

为了研究人肝细胞癌（HCC）的癌变过程，分析了HMGB1及其受体TLR-4随组织巨噬细胞（TAM）的变化。此外，还研究了 FrB 免疫毒素对抗 TAM 的有效性，是否可以减少肿瘤的恶性转化。在HCC中，HMGB1水平与TAM数量以及TAM数量与患者预后之间存在相关性。对于EMT的了解，转录因子ZEB-1也参与其中。另一方面，对裸鼠HepG2皮下移植模型给予FrB免疫毒素后，可见明显的促瘤作用。考虑到这些因素，有人认为HMGB1和衍生的TAM可能有助于HCC的恶性转化，而FrB免疫毒素可以作为一种治疗策略。

项目成果

Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer

• DOI: 10.1016/j.jss.2009.05.026
• 发表时间: 2011-05-01
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Kurahara, Hiroshi;Shinchi, Hiroyuki;Takao, Sonshin
• 通讯作者: Takao, Sonshin