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）：高级别神经胶质瘤的预后很严峻。目前的疗法只能适度延长生存期，因此人们对开发更好的靶向神经胶质瘤治疗方法非常感兴趣。 CRYAB 已被确定为候选神经胶质瘤癌基因，因为它在人类神经胶质瘤中经常过度表达。对已建立的神经胶质瘤细胞系的研究表明 CRYAB 在细胞凋亡和侵袭中发挥作用，然而，由于缺乏也可以模拟 CRYAB 对免疫系统潜在影响的动物研究，CRYAB 在神经胶质瘤发生和进展中的重要性仍不清楚。这里提出的研究将利用小鼠遗传模型来研究 Cryab 在体内、免疫活性、本土环境中对神经胶质瘤发生的影响。具体来说，将检查遗传性 Cryab 过度表达和缺失对神经胶质瘤易感遗传背景中神经胶质瘤形成的影响。将检查 Cryab 过度表达对细胞凋亡率和体内免疫细胞浸润的影响。这些研究预计将确定 CRYAB 在神经胶质瘤发生中的致癌作用，并为未来的研究奠定基础，以确定 CRYAB 调节药物是否可用作神经胶质瘤靶向治疗。