Mechanisms of liver carcinogenesis through phospho-Smad by gene-targeted mice

基因靶向小鼠通过磷酸化Smad导致肝癌的机制

• 批准号: 22390153
• 负责人: MATSUZAKI Koichi
• 金额: $ 11.48万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-22390153/
• 关键词: TGF-β; Smad; Liver fibrosis; Carcinogenesis; TGF-beta; JNK; CDK; シグナル伝達; 肝発がん; 肝線維化; 肝発癌

During progression of chronic liver diseases, chronic inflammation together with somatic mutations shifts hepatocytic phospho-Smad signaling from tumor-suppression to fibro-carcinogenesis, accelerating liver fibrosis and increasing risk of liver cancer. Patients with mild fibrosis respond effectively to therapy by successfully switching Smad phospho-isoform signaling from fibro-carcinogenesis to tumor-suppression, while other therapy responders with advanced liver fibrosis do not (Cytokine & Growth Factor Review in press; Hepatology Research Epub ahead of print).

在慢性肝病的进展过程中，慢性炎症和体细胞突变将肝细胞磷酸化Smad信号从抑制肿瘤转变为纤维致癌，加速了肝纤维化，增加了肝癌的风险。轻度纤维化的患者通过成功地将Smad磷酸异构体信号从纤维致癌转换为肿瘤抑制来对治疗做出有效反应，而其他晚期肝纤维化的治疗反应者则不能(细胞因子和生长因子综述在印刷中；肝病研究Epub在印刷中)。

项目成果

Expression of pituitary tumor transforming gene 1 (PTTG1)/securin in hepatitis B virus-associated liver diseases: Evidence for a hepatitis B virus X protein-mediated inhibition of PTTG1 ubiquitination and degradation.

乙型肝炎病毒相关肝病中垂体肿瘤转化基因 1 (PTTG1)/securin 的表达：乙型肝炎病毒 X 蛋白介导的 PTTG1 泛素化和降解抑制的证据。

• 发表时间: 2010
• 期刊: Hepatology 51
• 作者: Molina-Jimenez F;Benedicto I;Murata M;Martin-Vilchez S;Seki T;Pintor-Toro JA;Tortolero M;Moreno-Otero R;Okazaki K;Koike K;Barbero JL;Matsuzaki K;Majano PL;Lopez-Cabrera M.
• 通讯作者: Lopez-Cabrera M.

Smad phosphoisoform signaling specificity: the right place at the right time.

• DOI: 10.1093/carcin/bgr172
• 发表时间: 2011-11
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Matsuzaki K

Oncogenic Smad3 Signaling Induced by Chronic Inflammation Is an Early Event in Ulcerative Colitis-associated Carcinogenesis

• DOI: 10.1002/ibd.21395
• 发表时间: 2011-03-01
• 期刊: INFLAMMATORY BOWEL DISEASES
• 影响因子: 4.9
• 作者: Kawamata, Seiji;Matsuzaki, Koichi;Okazaki, Kazuichi
• 通讯作者: Okazaki, Kazuichi

Reversible or irreversible phospho-Smad2/3 signaling between tumor-suppression and fibro-carcinogenesis in hepatitis C virus-related chronic liver diseases

丙型肝炎病毒相关慢性肝病中肿瘤抑制和纤维癌发生之间的可逆或不可逆磷酸化Smad2/3信号传导

• 作者: Miki Murata;Koichi Matsuzaki
• 通讯作者: Koichi Matsuzaki

リンカー領域がリン酸化されたSmad3を特異的に認識するモノクローナル抗体

特异性识别具有磷酸化接头区域的 Smad3 的单克隆抗体

• 发表时间: 2012