Investigations of Cryab activity in gliomagenesis

胶质瘤发生中 Cryab 活性的研究

• 批准号: 8638324
• 负责人: Lara S Collier
• 金额: $ 7.53万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638324
• 关键词: Animals; Apoptosis; Apoptotic; Astrocytes; Backcrossings; Cells; Crystallins; Foundations; Future; Genetic; Genetic Engineering; Genetic Models; Glial Fibrillary Acidic Protein; Glioma; Gliomagenesis; Heat shock proteins; Human; Immune; Immune response; Immune system; Immunocompetent; Infiltration; Inflammatory; Investigation; Modeling; Molecular Chaperones; Monitor; Morbidity - disease rate; Mus; Oncogenes; Oncogenic; Pharmaceutical Preparations; Production; Protein Family; Proteins; Reaction; Research; Role; Stress; Study models; Therapeutic; Transgenic Mice; Transgenic Organisms; Up-Regulation; aged; cytokine; glioma cell line; in vivo; interest; member; mouse model; neoplastic cell; outcome forecast; public health relevance; response; tumor; tumor initiation; tumor microenvironment; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): High-grade gliomas carry a grim prognosis. Current therapies only modestly prolong survival and therefore there is great interest in developing better, targeted therapies for glioma treatment. CRYAB has been identified as a candidate glioma oncogene as it is frequently over-expressed in human gliomas. Studies in established glioma cell lines have indicated a role for CRYAB in apoptosis and invasion, however the importance of CRYAB in glioma initiation and progression remains unclear due to a paucity of animal studies where potential effects of CRYAB on the immune system can also be modeled. The research proposed here will utilize mouse genetic models to investigate the impact of Cryab on gliomagenesis in an in vivo, immunocompetent, autochthonous setting. Specifically, the impact of genetic Cryab over-expression and loss on glioma formation in a glioma pre-disposed genetic background will be examined. The effect of Cryab over-expression on apoptosis rates and immune cell infiltration in vivo will be examined. These studies are expected to establish an oncogenic role of CRYAB in gliomagenesis and to provide the foundation for future studies to determine if CRYAB-modulating drugs may have utility as glioma targeted therapies.

描述（由申请人提供）：高级神经胶质瘤带有严峻的预后。当前的疗法仅适度延长生存期，因此人们对开发更好的，有针对性的胶质瘤治疗疗法非常感兴趣。 Cryab已被确定为候选神经胶质瘤癌基因，因为它在人神经胶质瘤中经常过表达。在已建立的神经胶质瘤细胞系中的研究表明，Cryab在细胞凋亡和侵袭中的作用，但是由于动物研究的匮乏，Cryab在神经胶质瘤起始和进展中的重要性尚不清楚，在这些研究中，Cryab对免疫系统的潜在影响也可以进行建模。此处提出的研究将利用小鼠遗传模型研究Cryab对体内，免疫能力，自节体环境中神经胶质作用的影响。具体而言，将检查遗传冰显示过表达和丧失对神经胶质瘤预识别遗传背景中神经胶质瘤形成的影响。将检查Cryab过表达对体内凋亡率和免疫细胞浸润的影响。预计这些研究将确定Cryab在神经胶质作用中的致癌作用，并为将来的研究奠定基础，以确定Cryab调节药物是否具有效用为胶质瘤靶向疗法。