胆管癌における休眠がん細胞のメカニズムの解明

阐明胆管癌中休眠癌细胞的机制

• 批准号: 21K08725
• 负责人: 益田 邦洋
• 金额: $ 2.66万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K08725/
• 关键词: Fbxw7; 胆管癌; 休眠がん細胞; 癌幹細胞; がん幹細胞; FBXW7

胆管癌の転移再発や治療抵抗性に関与する休眠がん細胞を同定し,分子機構を関与を解明し,新規治療標的に発展させることである.休眠がん細胞は時間を経た再発転移機構であり,この仕組みに癌幹細胞(CSC)の関与が示されている.細胞周期の休止期に存在し,従来の化学療法に抵抗性を示す.Fbxw7は多くの癌で不活性型変異を認める癌抑制遺伝子で,血液癌や固形癌でFBXW7を介したCSCの制御が報告された.本研究はFbxw7による休眠がん細胞の制御メカニズムを解明し,治療標的にするという胆管癌の新たな治療戦略に発展させることを目的とする.(目的)胆管癌の転移再発や治療抵抗性に関与する休眠がん細胞を同定し,分子機構にFbxw7の関与を解明し,新規治療標的に発展させることである.休眠がん細胞は時間を経た再発転移機構であり,この仕組みに癌幹細胞(CSC)の関与が示されている.細胞周期の休止期に存在し,従来の化学療法に抵抗性を示す.Fbxw7は癌抑制遺伝子で,多くの癌で不活性型変異を認める.我々はFBXW7低下が予後不良因子であること,細胞株で基質の蓄積が進展と化学療法抵抗性に関与することを示した.近年,血液癌や固形癌でFBXW7基質c-MYCを介したCSCの制御が報告され,FBXW7抑制によるCSC治療の可能性が示された.本研究は術前治療後の胆管癌組織を用い,FBXW7発現上昇と治療抵抗性の関連性を検証し,細胞株,マウス実験でFbxw7による休眠がん細胞の制御メカニズムを解明し,治療標的にするという胆管癌の新たな治療戦略に発展させる.

The resistance of bile duct cancer transfer and re-treatment is the same as that of dormant bile duct cells, molecular mechanism and understanding, and the development of the new treatment protocol. Dormant cell cycle time transfer machine transfer machine to transfer the machine to transfer, the staff member to evaluate the cancer cell (CSC) and to show that the cancer cell is not available for use. The resting period of the cell cycle is present, and the chemical method is used to detect resistance. Fbxw7 multiple cancers, inactive cancers, cancer suppressors, hematological cancers, solid cancers, FBXW7, CSC. In this study, Fbxw7, hibernation, hibernation, hiber (objective) the resistance of bile duct cancer transfer and retreatment is the same as that of the dormant biliary cancer cell, and the molecular mechanism is the same as that of the dormant biliary cancer cell, and the molecular mechanism is different from that of the Fbxw7 treatment. Dormant cell cycle time transfer machine transfer machine to transfer the machine to transfer, the staff member to evaluate the cancer cell (CSC) and to show that the cancer cell is not available for use. The resting phase of the cell cycle is present, and the chemical method is used to show resistance. Fbxw7, cancer suppressors, multiple cancers, inactive cancers, multiple cancers. After the decrease of FBXW7, the adverse factors were affected, and the cell lines were detected by chemical resistance assay and chemical resistance test. In recent years, hematological cancer "solid cancer" FBXW7 c-MYC "CSC" is involved in the control of reports, and FBXW7 inhibition is associated with the possibility of CSC treatment. In this study, the tissue of cholangiocarcinoma was treated before and after surgery, and FBXW7 was used in the treatment of cholangiocarcinoma. in this study, the tissue tissue of cholangiocarcinoma was treated before and after surgery, and the new treatment of cholangiocarcinoma was improved. The cell line, Fbxw7 cell line, dormant cell, biliary cancer, cholangiocarcinoma, biliary carcinoma, cholangiocarcinoma, biliary duct, cholangiocarcinoma, biliary duct