Pathology

项目摘要 病理学核心（2）将提供无缝的翻译基础设施，以支持RS组织的研究 计划在这个应用程序中。这将包括体外扩增原代RS样本， 免疫受损小鼠，以努力产生体内RS primagraft模型，用于提供新鲜或冷冻的 用于体外分子和体内功能实验的RS细胞。RS样本将具有完整的临床注释 以及分子表征（来自项目1/核心3），并将从患者样本中获得 通过DFCI RS生物样本核心（1）存储的样本以及来自DFCI和合作机构的新入组患者 机构职能体系这些模型是一个重要的和日益受到赞赏的工具，用于分析新发现的 遗传病变，相关信号传导和生存途径，合理的治疗靶点和机制， 耐药性RS细胞将通过尾静脉注射或直接植入皮下或下方递送。 肾包膜然后，这些primagraft模型可以用于表征生物学和评估对 RS细胞的治疗。该病理学核心还将：（i）提供RS患者的FFPE存档样本，（ii） 提供用于后续研究的人类RS样品的组织病理学分析，（iii）产生组织 微阵列（和CLL/RS对的载玻片用于功能验证，（iv）提供形态学和组织病理学 在工程小鼠中分析小鼠RS样品，和（v）产生组织阵列和载玻片以研究 组织病理学和进行小鼠RS工程小鼠免疫组织化学表征。

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.