Pathology

项目摘要 这个病理学核心(2)将提供一个无缝的翻译基础设施来支持RS组织的研究 已在此应用程序中计划。这将包括主要RS样本的体外扩增 免疫功能低下的小鼠为提供新鲜或冷冻的RS原代移植模型而努力 RS细胞用于体外分子和体内功能实验。RS样本将有完整的临床注释 以及分子特征(来自项目1/核心3)，并将从患者样本中获得 通过DFCI RS Biosecimen Core(1)以及DFCI和协作中心新登记的患者进行存储 机构。这些模型是一种重要的、日益受到重视的分析新发现的 基因损伤，相关信号和生存通路，合理的治疗靶点和机制 抗药性。RS细胞将通过尾静脉注射或直接植入皮下或皮下 肾包膜。然后，这些原始模型可以用来描述生物学特征和评估对 RS细胞的治疗。该病理学核心还将：(I)提供来自RS患者的FFPE存档样本，(Ii) 提供人类RS样本的组织病理学分析，以用于后续研究，(Iii)产生组织 微阵列(和用于功能验证的CLL/RS对的载玻片)，(Iv)提供形态和组织病理学 对工程小鼠中的小鼠RS样本进行分析，以及(V)制作组织阵列和玻片进行研究 小鼠RS工程化小鼠的组织病理学和免疫组织化学鉴定。

Project Summary This Pathology Core (2) will provide a seamless translational infrastructure to support the research on RS tissues planned in this application. This will include the ex vivo expansion of primary RS samples in immunocompromised mice in an effort to generate in vivo RS primagraft models for provision of fresh or frozen RS cells for in vitro molecular and in vivo functional experiments. The RS samples will have full clinical annotation as well as molecular characterization (from Project 1/Core 3), and will be derived from patient samples already stored through the DFCI RS Biospecimen Core (1) as well as newly enrolled patients from DFCI and collaborating institutions. These models are a significant and increasingly appreciated tool for the analysis of newly identified genetic lesions, associated signaling and survival pathways, rational therapeutic targets and mechanisms of drug resistance. RS cells will be delivered by tail vein injection or directly implanted subcutaneously or beneath the renal capsule. These primagraft models could then be used to characterize biology and assess response to therapy of the RS cells. This Pathology Core will also: (i) provide FFPE archived samples from RS patients, (ii) provide histo-pathological analysis of human RS samples to be used in subsequent studies, (iii) generate tissue microarrays (and slides of CLL/RS pairs for functional validation, (iv) provide morphologic and histopathologic analysis of mouse RS samples in engineered mice, and (v) generate tissue arrays and slides to study histopathology and perform immunohistochemical characterization of mouse RS engineered mice.