Biospecimens and Patient-derived xenografts

核心1 -项目摘要 核心1的总体目标是提供银行所需的基础设施和专业知识， 原发性白血病、结肠癌和胰腺癌样本，建立患者来源的异种移植物（PDX）， 类器官和细胞模型，并使这些患者来源的资源可供所有计划研究者使用， 从而促进CSBC研究人员进行的翻译和实验室研究， 项目1和2。这两个项目都需要获得患者样本和来自PDX和类器官的细胞 模型核心支持3个功能：（1）冷冻保存和分配来自患者的原代细胞， 白血病、结肠癌和胰腺癌，（2）异种移植物建立、表征和分布， 类器官和这些疾病的细胞培养模型，以及（3）从原发性肿瘤中分离细胞群 用于单细胞分析的样品和组织模型。核心的职能包括文件编制和 跟踪知情同意，活组织、血浆或血清的分离和冷冻保存，以及基因组 患者样本的DNA并将样本分发给CSBC研究人员。大量原发性 白血病、结肠和胰腺肿瘤样本目前可在我们现有的储存库中获得， 项目调查员。将从我们的常规评估患者中采集额外样本。 胃肠道肿瘤和血液恶性肿瘤诊所。除了将原代细胞分配给 作为项目调查人员，核心1还将维护和分发一个被选中的具有良好特征的PDX库， 在免疫受损小鼠中传代。移植白血病细胞和原发性上皮肿瘤的方法 免疫缺陷小鼠的组织现在已经很好地建立，我们和其他人已经成功地使用PDX 毒品测试的模型。类器官培养方法将用于补充PDX工作，并将 提供了增殖和分离患者来源的上皮肿瘤细胞和间质肿瘤细胞的另一种方法， 细胞核心1将维护一个PDX模型和类器官库，并分发给项目研究者， needed.核心1将由威廉·哈恩博士和大卫·温斯托克博士共同指导。哈恩医生是一名医生 DFCI癌症基因组发现中心（CCGD）的肿瘤学家。他还与 DFCI胃肠肿瘤科，并帮助建立了类器官和PDX储存库 来源于原发性和转移性胰腺癌和结肠癌样品。与CCGD合作，博士。 哈恩的实验室已经创建了一个管道，用于对同意的患者来源的基因组进行表征。 样品Weinstock博士是一名医学肿瘤学家，负责DFCI血液学检查PDX库， 其已经包含超过200个已经冷冻保存的可移植白血病PDX模型， 进行全基因组转录组分析，靶向DNA测序，免疫表型分析， 额外的分子表征。因此，核心1在处理方面具有丰富的经验， 冷冻保存、流式细胞术分析、纯化、繁殖、建库和基因组表征 原代标本和肿瘤模型，以及它们在临床前药物评价中的用途。

Core 1 – Project Summary The overarching goal of Core 1 is to provide the infrastructure and professional expertise needed to bank primary leukemia, colon, and pancreatic cancer specimens, establish patient-derived xenograft (PDX), organoid, and cell models, and make these patient-derived resources available to all Program investigators, thereby facilitating the translational and laboratory-based research performed by CSBC investigators in Projects 1 and 2. Both projects will require access to patient samples and cells derived from PDX and organoid models. The core supports 3 functions: (1) cryopreservation and distribution of primary cells from patients with leukemia, colon, and pancreatic cancer, (2) establishment, characterization, and distribution of xenograft, organoid, and cell culture models of these diseases, and (3) isolation of cell populations from primary tumor samples and tissue models for single cell analysis. The functions of the core include documentation and tracking of informed consent, isolation and cryopreservation of viable tissue, plasma or serum, and genomic DNA from patient samples and distribution of samples to CSBC investigators. A large number of primary leukemia, colon and pancreatic tumor samples are currently available in our existing repositories for use by Project Investigators. Additional samples will be acquired from patients routinely evaluated in our gastrointestinal oncologic and hematologic malignancies clinics. In addition to distributing primary cells to program investigators, Core 1 will also maintain and distribute a bank of well characterized PDXs selected for passage in immunocompromised mice. Methods for engrafting leukemia cells and primary epithelial tumor tissues in immunodeficient mice are now well established, and we and others have successfully used PDX models for drug testing. Organoid culture approaches will be used to complement the PDX effort, and will provide an additional way of propagating and segregating patient-derived epithelial tumor cells and stromal cells. Core 1 will maintain a bank of PDX models and organoids and distribute to program investigators as needed. Core 1 will be jointly directed by Drs. William Hahn and Dr. David Weinstock. Dr. Hahn is a medical oncologist who directs the DFCI Center for Cancer Genome Discovery (CCGD). He also works closely with the Division of Gastrointestinal Oncology at DFCI and has helped establish an organoid and PDX repository derived from primary and metastatic pancreatic and colon cancer samples. Working with the CCGD, Dr. Hahn's laboratory has created a pipeline for the genomic characterization of consented patient derived samples. Dr. Weinstock is a medical oncologist and directs the DFCI Hematologic Malignancy PDX repository, which already contains >200 transplantable leukemia PDX models that have been cryopreserved and undergone genome-wide transcriptome analysis, targeted DNA sequencing, immunophenotyping, and additional molecular characterization. Thus, Core 1 has extensive experience in the processing, cryopreservation, flow cytometric analysis, purification, propagation, banking, and genomic characterization of primary specimens and tumor models, as well as their use in preclinical drug evaluation.