Experimental Therapeutics and BioMonitoring for Brain Tumors

脑肿瘤的实验治疗和生物监测

• 批准号: 8227507
• 负责人: FRED H HOCHBERG
• 金额: $ 139.33万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8227507
• 关键词: Experimental; Therapeutics; BioMonitoring; Brain; Tumors

DESCRIPTION (provided by applicant): The goals of this proposal are to improve treatment for gliomas by enhancement of oncolytic therapy and to develop serum microvesicles as biomarkers for genetic and phenotypic properties of individual GBM tumors and their response to therapy. Project 1 (Chiocca/Kaur) will evaluate whether viral RNA in microvesicles produced by HSV-infected glioma cells increases susceptibility of tumors to oncolysis, and assess viral and cellular mRNAs in tumor-derived serum microvesicles as biomarkers of oncolytic therapy. Project 2 (Weissleder/Hahko) will apply nanotechnology-based diagnostic magnetic resonance (DMR) to characterize micro vesicle number and antigenic profiles in serum based on proteins critical to oncogenesis using serum from mice and patients bearing glioblastoma (GBM) and undergoing different treatment paradigms. Project 3 (Breakefield) will characterize and enrich tumor-derived microvesicles serum using antibody-capture microfluidic chambers and quantities levels and mutations in GBM-related RNAs using serum samples as in Project 2. These projects will be supported by: Core A (Hochberg) to provide oversight for programmatic organization and neuropathology; Core B (Carter) to maintain a biorepository of human GBM tumor and longitudinal serum samples from patients undergoing standard-of-care therapy or clinical Phase l/ll trials, to supply de-identified samples to Project 2 and 3, and to carry out biostatistical correlations with clinical parameters; and Core C (Charest) to provide genetically engineered GBM mice with mutations representing driver mutations in two subtypes of human GBMs to Project 1, and de-identified tumor/serum samples and biostatistical correlations with tumor volume and survival time to Projects 2 and 3. This program will develop and evaluate new accessible serum biomarkers to facilitate evaluation of therapeutic paradigms in mouse models and human patients both in terms of real time response to therapy and mechanisms of resistance to therapy.

描述（由申请人提供）：该提案的目标是通过增强溶瘤治疗来改善神经胶质瘤的治疗，并开发血清微泡作为个体 GBM 肿瘤的遗传和表型特性及其对治疗的反应的生物标志物。项目 1 (Chiocca/Kaur) 将评估 HSV 感染的神经胶质瘤细胞产生的微泡中的病毒 RNA 是否会增加肿瘤对溶瘤的敏感性，并评估肿瘤来源的血清微泡中的病毒和细胞 mRNA 作为溶瘤治疗的生物标志物。项目 2（Weissleder/Hahko）将应用基于纳米技术的诊断磁共振（DMR）来表征血清中的微囊泡数量和抗原谱，基于对肿瘤发生至关重要的蛋白质，使用来自患有胶质母细胞瘤（GBM）的小鼠和患者的血清并接受不同的治疗模式。项目 3 (Breakefield) 将使用抗体捕获微流体室来表征和富集肿瘤来源的微泡血清，并使用项目 2 中的血清样本来表征 GBM 相关 RNA 的数量水平和突变。这些项目将得到以下支持：Core A (Hochberg)为规划组织和神经病理学提供监督；核心 B (卡特) 维护人类 GBM 肿瘤和接受标准护理治疗或临床 I/II 期试验的患者的纵向血清样本的生物储存库，为项目 2 和 3 提供去识别化样本，并进行与临床参数的生物统计相关性； Core C (Charest) 为项目 1 提供代表人类 GBM 两种亚型驱动突变的基因工程 GBM 小鼠，为项目 2 和 3 提供去鉴定的肿瘤/血清样本以及与肿瘤体积和生存时间的生物统计相关性。该计划将开发和评估新的可访问的血清生物标志物，以促进对小鼠模型和人类患者的治疗范例在对治疗的实时反应和治疗耐药机制方面的评估。