Elucidation of activation mechanism of insulin-like growth factor and development of therapy using neutralizing antibody in the gastrointestinal cancers

阐明胰岛素样生长因子的激活机制并开发使用中和抗体治疗胃肠道癌症的疗法

• 批准号: 23590939
• 负责人: MIYAMOTO Shin'ichi
• 金额: $ 3.16万
• 依托单位: Kyoto 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-23590939/
• 关键词: がん; シグナル伝達; 分子標的薬; インスリン様増殖因子; 中和抗体; 分子標的治療; 腫瘍微小環境; バイオマーカー; 活性型インスリン様増殖因子; 肝転移

It is necessary for the cancer cells to adapt to the tissue microenvironment for the metastasis formation in other ogans. Colon cancer cells highly metastasize to the liver and control of liver metastasis is most important issue in the therapeutic strategy of colon cancer. We clarified that liver-derived insulin-like growth factors (IGFs) activated by cancer-producing protease play an important role for the liver metastasis formation and could be a therapeutic target using neutralizing antibody. Furthermore, we developed the measurement system of activted (bioactive) IGF in the blood and demonstrated that bioactive IGF was increased with progressio of liver metastais and could be a biomarker of IGF neutralizing strategy in the mouse model.

癌细胞有必要适应其他OGAN中的转移形成的组织微环境。在结肠癌治疗策略中，结肠癌细胞高度转移至肝脏转移是最重要的问题。我们澄清说，通过癌症产生蛋白酶激活的肝脏衍生的胰岛素样生长因子（IGF）对肝转移的形成起着重要作用，并且可以使用中和抗体成为治疗靶标。此外，我们开发了血液中激活（生物活性）IGF的测量系统，并证明随着肝转移的进度，生物活性IGF增加了，并且可能是小鼠模型中IGF中和策略的生物标志物。

项目成果

京都大学医学部附属病院 武藤学研究室

京都大学医院武藤学实验室

Pharmacokinetics of oxaliplatin in a hemodialytic patient treated with modified FOLFOX-6 plus bevacizumab therapy

• DOI: 10.1007/s00280-011-1633-9
• 发表时间: 2011-07-01
• 期刊: CANCER CHEMOTHERAPY AND PHARMACOLOGY
• 影响因子: 3
• 作者: Horimatsu, Takahiro;Miyamoto, Shin'ichi;Chiba, Tsutomu
• 通讯作者: Chiba, Tsutomu

Multimodal endoscopic treatment for delayed severe esophageal stricture caused by incomplete stent removal

多模态内镜治疗支架取出不全所致迟发性严重食管狭窄

• DOI: 10.1111/dote.12041
• 发表时间: 2014
• 期刊: Dis Esophagus
• 影响因子: 2.6
• 作者: Setoyma T;Miyamoto S;Horimatsu T;Morita S;Ezoe Y;Muto M;Watanabe G;Tanaka E;Chiba T
• 通讯作者: Chiba T

An unusual cause of dysphagia after endoscopic resection of an early esophageal cancer

早期食管癌内镜切除术后吞咽困难的一个不寻常原因

• DOI: 10.1055/s-0030-1256260
• 发表时间: 2011
• 期刊: Endoscopy
• 影响因子: 9.3
• 作者: Nakanishi Y;Miyamoto S;Ishizu S;Seno H;Muto M;Chiba T
• 通讯作者: Chiba T

Early Detection of 5-FU-induced Acute Leukoencephalopathy on Diffusion-Weighted MRI

• DOI: 10.1093/jjco/hyq157
• 发表时间: 2011-01-01
• 期刊: JAPANESE JOURNAL OF CLINICAL ONCOLOGY
• 影响因子: 2.4
• 作者: Akitake, Reiko;Miyamoto, Shin'ichi;Chiba, Tsutomu
• 通讯作者: Chiba, Tsutomu