多发性骨髓瘤细胞对 mTOR 抑制剂的敏感性-猫眼课题宝

多发性骨髓瘤细胞对 mTOR 抑制剂的敏感性

批准号：

8484360

负责人：

ALAN K LICHTENSTEIN

金额：

$17.32万

依托单位：

BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE

依托单位国家：

美国

项目类别：

财政年份：

2005

资助国家：

美国

项目状态：

已结题

起止时间：

2005-06-01 至 2017-04-30

来源：

https://reporter.nih.gov/project-details/8484360

关键词：

1-Phosphatidylinositol 3-Kinase Active Sites Address Apoptosis Binding Binding Proteins Binding Sites Biological Assay Categories Cell Cycle Cell Cycle Proteins Cell Line Cell Survival Cells Cessation of life Complex Data Development Drug usage Event Feedback Future G1 Arrest Generations Goals Growth Hybrids In Vitro Malignant - descriptor Malignant Neoplasms Mediating Molecular Multiple Myeloma Multiprotein Complexes Mus New Agents PI3K/AKT Patients Pharmaceutical Preparations Phosphorylation Phosphotransferases Plasma Cells Proteins Proto-Oncogene Proteins c-akt Raptors Repression Role Signal Transduction Sirolimus Site Specimen Tacrolimus Binding Protein 1A Testing Therapeutic Translations Work Yeasts cell type design drug sensitivity endoplasmic reticulum stress expectation human FRAP1 protein in vivo Model inhibitor/antagonist kinase inhibitor knock-down mTOR Inhibitor novel overexpression pre-clinical prevent protein expression protein protein interaction research study resistance mechanism therapeutic target transcription factor

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中文摘要

翻译

描述(由申请人提供)：项目摘要/ASBTRACT该项目的主要目标是为多发性骨髓瘤患者未来靶向治疗TORC2多蛋白复合体提供理论依据。目的包括研究mTOR激酶抑制剂在体外和体内对骨髓瘤细胞株和患者原代细胞标本的作用，确定关键的TORC2底物作为抑制的关键靶点，并测试DEPTOR蛋白表达在调节骨髓瘤细胞对TORC2抑制剂敏感性中的作用。骨髓瘤细胞的存活和死亡以及它们在体外的黏附和迁移能力将被研究。还将尝试鉴定和开发防止TORC2复合体内蛋白质-蛋白质相互作用的新化合物。

英文摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ASBTRACT The main objective of this project is to provide a rationale for future therapeutic targeting of the TORC2 multiprotein complex in patients with multiple myeloma. The aims include studying mTOR kinase inhibitors against myeloma cell lines and patient primary cell specimens in vitro and in murine models in vivo, identifying the key TORC2 substrates that are the critical targets for inhibition and testing the role of DEPTOR protein expression in regulating the sensitivity of myeloma cells to TORC2 inhibitors. The viability versus death of myeloma cells as well as their ability to adhere and migrate in vitro will be studied. The identification and development of novel compounds which prevent protein-protein interactions within the TORC2 complex will also be attempted.

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