Core 1: Biospecimens Core

摘要--生物质学家核心 生物质学家核心将作为一个中央资源，协调提供高度翻译的 相关的动物和人类分析标本，用于两个主要研究项目和可能的几个 预期的试点项目。最大限度地提高对动物进行的分析的翻译相关性 标本、患者来源的异种移植(PDX)和基因工程小鼠模型(GEMM) 胶质母细胞瘤(GBM)将用于我们的临床前研究。我们有使用这些模型的丰富经验 用于评估颅内肿瘤的系统生物学和药物操作如何失调 这些系统中的关键信令节点。再加上这些临床前研究，分析手术 来自GBM患者的样本为所进行的生物学建模提供了“地面事实”。在这方面， Biosecimens Core将利用与DFCI和DFCI的神经外科医生建立的合作 梅奥诊所和广泛的神经肿瘤学生物库，可在梅奥诊所提供这两个档案 肿瘤样本和对影像登记的新鲜手术样本的前瞻性分析。派生细胞， 来自动物和人类生物标本的有机物和组织切片培养也将用于 对关键调查结果进行反向翻译，并进一步完善或验证我们的系统分析。利用这一点 在两个项目中协调分析相同生物样本的机会，科学 经理将协调生物素的收集、质量保证审查、发货和分析 实验室和项目。该核心还将确保适当的监管审查和批准到位 以支持动物和人类生物标本的收集和分析。核心的整体努力 可以分为两个目的来支持动物和人类的基底膜研究。 具体目标1：在荷瘤动物中开发、管理和执行体内研究 具体目标2：协调人类生物寄生虫的收集和分配

ABSTRACT – BIOSPECIMENS CORE The Biospecimens Core will serve as a central resource to coordinate provision of highly translationally relevant animal and human analytical specimens for use in both main research projects and likely several of the anticipated pilot projects. To maximize the translation relevance of the analyses performed on animal specimens, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs) of glioblastoma (GBM) will be used for our pre-clinical studies. We have extensive experience using these models for evaluating the systems biology of intracranial tumors and how pharmacologic manipulations dysregulate critical signaling nodes within these systems. Coupled with these preclinical studies, analysis of operative specimens from GBM patients provides a ‘ground-truth’ for the biological modeling performed. In this context, the Biospecimens Core will capitalize on established collaborations with neurosurgeons at both DFCI and Mayo Clinic and the extensive Neuro-Oncology Biobank available at Mayo Clinic for provision of both archived tumor samples and prospective analysis of image-registered, fresh operative specimens. Derivative cell, organoid, and tissue-slice cultures from both animal and human biospecimens also will be used to enable reverse translation of key findings and to further refine or validate our systems analyses. To capitalize on opportunities for coordinated analyses of the same biological samples across both Projects, a Scientific Manager will coordinate biospecimen collection, quality assurance review, shipment and analyses across laboratories and projects. The Core also will ensure appropriate regulatory review and approvals are in place to support both the animal and human biospecimen collections and analyses. The overall efforts of the Core can be divided into two Aims to support animal and human GBM studies. Specific Aim 1: Develop, manage, and execute in vivo studies in tumor-bearing animals Specific Aim 2: Coordinate the collection and distribution of human biospecimens