Core 2: PDX Tumor Core

核心2：PDX肿瘤核心

• 批准号: 8866969
• 负责人: Andrew P Mazar
• 金额: $ 8.85万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-19 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8866969
• 关键词: Acute Myelocytic Leukemia; Animal Model; Appearance; Back; Breast; Cancer Center; Cancer Patient; Cell Line; Cells; Characteristics; Chicago; Chromatin; Chromatin Loop; Chromosomes; Clinical; Core Facility; Developmental Therapeutics Program; Elements; Engraftment; Enhancers; Evaluation; FLT3 gene; Functional disorder; Gene Expression; Glioma; Growth; Harvest; Histologic; Histology; Human; Image; In Vitro; Institutional Review Boards; Interphase; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Mechanics; Mitosis; Modeling; Molecular Profiling; Monitor; Multiple Myeloma; Mus; Mutation; Pathologist; Pathology; Patients; Plastics; Potassium; Potassium Channel; Process; Research Infrastructure; Research Personnel; Research Project Grants; Role; Sampling; Source; Specimen; Structure; Testing; Therapeutic; Time; Tissues; Tumor Cell Line; Tumorigenicity; Universities; Validation; Variant; Xenograft Model; Xenograft procedure; abstracting; base; cell growth; cell type; chromatin protein; cohesin; condensin; data integration; design; direct application; drug sensitivity; in vivo; malignant breast neoplasm; medulloblastoma; neoplastic cell; programs; repository; research study; tissue culture; tumor; tumor progression; tumor xenograft; tumorigenesis

ABSTRACT (PATIENT-DERIVED XENOGRAFT CORE) The Patient-Derived Xenograft (PDX) Core will support the efforts of the Chicago Region-PSOC to define the role of the spatio-temporal organization of chromatin in information transfer in cancer by providing CR-PSOC investigators with a valuable model of human cancer that will enable investigators to extend their observations to actual patient tumor cells. The Core will create and maintain carefully delineated, in vivo human tumor models from a broad range of histologies that retain the characteristics of fresh human tumors. These PDX models are passaged continuously in vivo and are never exposed to tissue culture plastic and the limitations imposed by tissue culture selection of certain tumor cell clones. The PDX tumors retain histological characteristics that are similar to the patient tumors from which they were derived. Thus, these models are thought to be closer to the clinical situation than traditional xenograft models. Models will be available to investigators across the PS-ON. The Core will build on an already established PDX repository infrastructure that currently maintains sixty-two models covering ten different tumor histologies, with 2-3 new models are created each week. Early passage cell lines are created in parallel from these in vivo PDX models and they will also be available to the CR-PSOC investigators, as well as potentially to investigators in the PS-ON. These early passage cell lines will be utilized for in vitro experiments by all three CR-PSOC research projects. The phenotypic and genotypic uniformity of these cells will enable integration of data that across the three projects. The PDX Core will provide tissue and cell lines, where available, from existing breast cancer and glioma PDX to Project 1 investigators for in vivo characterization of subcellular metallome imbalances as potential quantitative markers of tumorigenicity. In addition, the Core will create new PDX models of human multiple myeloma and medulloblastoma since potassium imbalances have been implicated in the tumorigenicity and progression of these tumor types. PDX models will also be used by Project 1 investigators for imaging studies and to evaluate the therapeutic potential of targeting K+ channels support the imaging studies. The Core will develop acute myeloid leukemia (AML) and bladder cancer PDX models and cells for use by Project 2 to study the relationship between enhancer dysfunction and cancer. The Core will provide Project 3 investigators with cell lines derived from various PDX to enable determination of the relationship of variation of the distribution of condensin, cohesin, and SMC5/6 in chromosomes during interphase and mitosis with variations in chromosome mechanics across human tumor cell types.

摘要（患者源性异种移植物芯） 患者源性异种移植物（PDX）核心将支持芝加哥地区PSOC的工作， 通过提供CR-PSOC，染色质的时空组织在癌症信息传递中的作用 研究人员将获得一个有价值的人类癌症模型，这将使研究人员能够扩展他们的观察 to actual实际patient病人tumor肿瘤cells细胞.核心将创建并维持精心划定的体内人类肿瘤 来自广泛的组织学模型，保留了新鲜人类肿瘤的特征。这些PDX 模型在体内连续传代，从不暴露于组织培养塑料， 这是由某些肿瘤细胞克隆的组织培养选择所强加的。PDX肿瘤在组织学上 这些特征与它们所来源的患者肿瘤相似。因此，这些模型是 被认为比传统的异种移植模型更接近临床情况。模型将提供给 调查人员在PS-ON。 核心将建立在一个已经建立的PDX存储库基础设施上，该基础设施目前维护着62个 覆盖10种不同肿瘤组织学的模型，每周创建2-3个新模型。早日通过 从这些体内PDX模型中平行创建细胞系，它们也将可用于CR-PSOC 这些早期传代细胞系将被用于 所有三个CR-PSOC研究项目的体外实验。表型和基因型一致性 这些单元将能够整合三个项目的数据。PDX核心将提供组织和 现有乳腺癌和神经胶质瘤PDX的细胞系（如可用）提供给项目1研究者进行体内研究 亚细胞金属组不平衡的表征作为致瘤性的潜在定量标志物。在 此外，核心将创建新的人类多发性骨髓瘤和髓母细胞瘤的PDX模型， 钾失衡与这些肿瘤类型的致瘤性和进展有关。PDX 项目1的研究者也将使用这些模型进行成像研究和评估治疗潜力 靶向K+通道支持成像研究。核心将发展为急性髓细胞白血病（AML） 和膀胱癌PDX模型和细胞用于项目2研究增强子之间的关系 功能障碍和癌症。核心将为项目3研究者提供来自各种PDX的细胞系 为了能够确定在细胞中凝聚素、粘附素和SMC 5/6的分布变化的关系， 间期和有丝分裂期染色体与人类肿瘤染色体力学的变化 细胞类型。