Investigations of Cryab activity in gliomagenesis

描述（申请人提供）：高级别胶质瘤预后恶劣。目前的治疗方法只能适度地延长生存期，因此开发更好的靶向治疗胶质瘤的兴趣很大。CRYAB已被确定为候选胶质瘤癌基因，因为它在人类胶质瘤中经常过表达。对已建立的胶质瘤细胞系的研究表明，CRYAB在细胞凋亡和侵袭中起作用，然而，由于缺乏动物研究，CRYAB对免疫系统的潜在影响也可以建模，因此CRYAB在胶质瘤发生和进展中的重要性仍不清楚。本文提出的研究将利用小鼠遗传模型来研究Cryab对胶质瘤形成的影响，在体内，免疫能力，自体环境中。具体来说，基因Cryab过表达和缺失对胶质瘤形成的影响将在胶质瘤预先处理的遗传背景下进行检查。在体内研究Cryab过表达对细胞凋亡率和免疫细胞浸润的影响。这些研究有望确定CRYAB在胶质瘤形成中的致癌作用，并为未来研究确定CRYAB调节药物是否可作为胶质瘤靶向治疗的药物提供基础。

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.