BRAIN TUMOR SPORT GRANT

脑肿瘤运动补助金

• 批准号: 8514309
• 负责人: John K. Wiencke
• 金额: $ 27.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514309
• 关键词: Active Immunotherapy; Address; Animals; BRAF gene; Biological Markers; Biometry; Brain Neoplasms; Characteristics; Childhood Brain Neoplasm; Clinical; Clinical Trials; Comprehensive Cancer Center; Cyclin-Dependent Kinase Inhibitor; Development; Diagnosis; Disease; Failure; Family; Funding; Gene Mutation; Genes; Genetic Variation; Genomics; Glioma; Goals; Grant; Heart; Heat shock proteins; Image; Immunotherapy; Incidence; Individual; Instruction; Knowledge; Learning; Link; MEKs; Malignant neoplasm of brain; Modality; Molecular; Mutation; Mutation Analysis; Neurosurgeon; Oncologist; Outcome; Pathology; Pathway interactions; Patients; Phase I Clinical Trials; Phase II Clinical Trials; Population; Population Sciences; Process; Publishing; Recurrence; Regulatory T-Lymphocyte; Reproduction spores; Research; Research Personnel; Research Project Grants; Seminal; Signal Transduction; Sports; T-Lymphocyte; Techniques; Therapeutic; Time; Tissues; Translational Research; Vaccines; Work; base; career development; comparative efficacy; genome wide association study; human FRAP1 protein; improved; inhibitor/antagonist; innovation; macrophage; mortality; mutant; neuro-oncology; novel; oncology program; pre-clinical; preclinical study; programs; response; tool; tumor; tumor immunology

PROJECT SUMMARY (See instructions): This revised SPORE renewal application represents the efforts of interdisciplinary teams of investigators from the Neuro-Oncology Program ofthe UCSF Helen Diller Family Comprehensive Cancer Center to apply their expertise to translational research focused on brain cancer. The proposal has four overall specific objectives: 1) to identify factors that contribute to the likelihood of surviving brain cancer; 2) to identify Imaging parameters and linked tissue biomarkers that predict recurrence and outcome in patients with low grade glioma; 3) to develop improved therapies for pediatric brain tumors harboring BRAF mutations; and 4) to improve immunotherapy for brain cancer. At the heart of the proposal are four translational research projects. Project 1 will identify genetic variations associated with survival in low-grade glioma and GBM patients, and will integrate survival genes identified in genome-wide association studies with IDH mutation and other molecular characteristics in the best example of integrative genomics pertaining to glioma survival to date. Project 2 will assess the ability of the spectroscopic markers identified in the previous funding period to predict time to progression and overall survival in low-grade glioma patients. The project also includes a first-ever analysis of the mutations that drive low-grade glioma formation and progression and which may help link genetic alterations to the spectroscopic changes noted. Project 3 is new to this proposal and will build on seminal studies that identified BRAF mutations in pediatric brain tumors. The project will preclinically evaluate new combinations of mechanism-based BRAF, MEK, and cyclin-dependent kinase inhibitors as well as initiate the first clinical trials of BRAF inhibitors in the pediatric brain tumor population. Project 4 will determine the impact of the PI(3)Ky/B7-H1 pathway on expansion of immunomodulatory T-cells and macrophages, and will investigate the utility of inhibiting PI(3)K/B7-H1 to augment immunotherapy in a clinical trial for GBM patients. This SPORE proposal also requests support for the Career Development and Developmental Research Programs, and four Cores (Administrative, Biospecimen/Pathology, Animal, and Biostatistics and Clinical) that will support the efforts of the four projects.

项目摘要（请参阅说明）：此修订后的孢子更新应用代表了UCSF Helen Diller Family综合癌症中心的神经肿瘤学计划的研究人员跨学科团队的努力，将其专业知识应用于转化研究，重点是脑癌。该提案具有四个总体特定目标：1）确定导致生存脑癌可能性的因素； 2）鉴定成像参数和连接的组织生物标志物，以预测低级神经胶质瘤患者的复发和结果； 3）开发改善携带BRAF突变的小儿脑肿瘤的疗法； 4）改善脑癌的免疫疗法。该提案的核心是四个转化研究项目。项目1将确定与低级神经胶质瘤和GBM患者生存有关的遗传变异，并将在全基因组关联研究中与IDH突变和其他分子特征鉴定出的生存基因，这是迄今为止综合基因组学的最佳实例与胶质瘤生存有关的综合基因组学。项目2将评估上一个资金期间鉴定出的光谱标志物的能力，以预测低级神经胶质瘤患者的进展时间和整体存活时间。该项目还包括对驱动低级神经胶质瘤形成和进展的突变进行的首次分析，并可能有助于将遗传变化与所指出的光谱变化联系起来。项目3是该提案的新事物，将基于确定小儿脑肿瘤中BRAF突变的开创性研究。该项目将临时评估基于机制的BRAF，MEK和细胞周期蛋白依赖性激酶抑制剂的新组合，并启动小儿脑肿瘤群中BRAF抑制剂的首次临床试验。项目4将确定PI（3）KY/B7-H1途径对免疫调节性T细胞和巨噬细胞扩展的影响，并将研究抑制PI（3）K/B7-H1对GBM患者临床试验中抑制PI（3）K/B7-H1的实用性。该孢子提案还要求支持职业发展和发展研究计划，以及四个核心（行政，生物测试/病理学，动物和生物统计学和临床​​），这些核心将支持这四个项目的努力。