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Pathology

病理

基本信息

批准号：
10491163
负责人：
RUBEN D CARRASCO
金额：
$ 11.42万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10491163
关键词：
Address Archives Area Automobile Driving B-Cell Antigen Receptor Biologic Characteristic Biological Biology Biopsy Cell Line Cells Chemotherapy-Oncologic Procedure Chronic Lymphocytic Leukemia Clinical Clinical Trials Complication Data Development Diagnosis Diagnostic Disease Disease model Dissection Doctor of Philosophy Documentation Drug resistance Engineering Engraftment Enrollment Evaluation Fibrous capsule of kidney Formalin Foundations Freezing Future Genetic Genetic Polymorphism Genome Genomics Goals Grant Hematologic Neoplasms Hematopathology Hematopoietic stem cells Histologic Histopathology Human Human Resources Immunocompromised Host Immunodeficient Mouse Immunohistochemistry Implant In Vitro Infrastructure Injections Institution Investigation Lesion Lymphoma MS4A1 gene Malignant Neoplasms Mission Modeling Molecular Morphology Mus Operative Surgical Procedures PTPRC gene Paraffin Embedding Pathogenesis Pathologic Pathology Pathway interactions Patient-Focused Outcomes Patients Phenotype Preparation Procedures Process Proteomics Receptor Gene Refractory Reporting Research Research Personnel Research Support Resources Rest Richter&apos s Syndrome Risk Sampling Signal Transduction Site Slide Small-Cell Lymphoma Solid Specimen Stereotyping Study Section Tail Testing Tissue Microarray Tissues Translations Transplantation Tumor Bank Validation Variant Veins base candidate validation cell bank chromosome 13q loss del(17p13)design effective therapy experimental study genome editing implantation improved in vivo in vivo Model innovation interest large cell Diffuse non-Hodgkin&apos s lymphoma lymphoid neoplasm mouse model novel novel marker patient derived xenograft model phenome pre-clinical programs prospective sample archive subcutaneous therapeutic target tissue resource tool transcriptomics treatment response tumor tumor microenvironment

项目摘要

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.

项目概要该病理学核心 (2) 将提供无缝转化基础设施来支持 RS 组织的研究计划在此应用程序中。这将包括初级 RS 样本的离体扩增免疫功能低下的小鼠试图生成体内 RS primaraft 模型，以提供新鲜或冷冻的 RS细胞用于体外分子和体内功能实验。 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），并将源自已经存在的患者样本通过 DFCI RS 生物样本核心 (1) 存储，以及来自 DFCI 和合作的新登记患者机构。这些模型是分析新发现的重要且越来越受赞赏的工具。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输送或直接植入皮下或下方肾被膜。然后，这些原代移植物模型可用于表征生物学并评估对 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) 提供用于后续研究的人类 RS 样本的组织病理学分析，(iii) 生成组织微阵列（以及用于功能验证的 CLL/RS 对的载玻片，(iv) 提供形态学和组织病理学数据分析工程小鼠中的小鼠 RS 样本，以及 (v) 生成组织阵列和载玻片以供研究对小鼠 RS 工程小鼠进行组织病理学分析并进行免疫组织化学表征。