Four-Dimensional Heterogeneity of Fluid Phase Biopsies in Cancer (4DB-Center)

癌症中液相活检的四维异质性（4DB-中心）

• 批准号: 8517232
• 负责人: PETER KUHN
• 金额: $ 1.86万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8517232
• 关键词: Biopsy; Blood; Cancer Patient; Cells; Cessation of life; Clinical; Complex; Databases; Diagnostic Neoplasm Staging; Dimensions; Disease; Disseminated Malignant Neoplasm; Epithelial; Four-dimensional; Generations; Genomics; Goals; Heterogeneity; Human; Instruction; Investigation; Liquid substance; Malignant Neoplasms; Mathematics; Measurement; Measures; Mechanics; Modeling; Morphology; Motion; Neoplasm Metastasis; Pathologic; Patients; Phase; Physics; Primary Neoplasm; Process; Property; Research Project Grants; Sampling; Solid; Stream; Therapeutic; Time; Training and Education; Travel; anticancer research; base; cancer cell; cell behavior; cohort; mathematical model; mathematical theory; neoplastic cell; neuronal cell body; predictive modeling; simulation; transcriptomics; tumor

Cancer metastasis via the blood stream can be modeled as a problem of fluid-solid interaction with multiple bodies (cells) of different masses, momentum, and physical qualities, in motion, within a complex flow field. The Four Dimensional Biopsy Center (4DB) utilizes physics-based measurements, mathematical modeling and numerical simulation to empirically characterize actual human cancer patient samples, with a goal of establishing a highly predictive model of human cancer cell behavior that will fundamentally alter our current understanding of the mechanisms of cancer metastasis. Extensive empirical measurements and analyses will be performed on a coherent set of samples from human cancer patients. Samples will consist of cells from primary tumors, locoregional metastases, and circulating tumor cells (CTCs) over time, all collected from the same patient. Additionally, a second cohort of samples will consist of CTCs from a large set of patients, stratified by tumor type and cancer stage. These sample sets will be analyzed in parallel by three independent Research Projects (RPs), producing orthogonal measures of identical phenomena, and delivering the variables and the correlations on the space and time dimension of epithelial cancers. The three Research Projects (RP) are: RP1 Cytophysics, which determines the physical and mechanical properties of cancer cells; RP2 Topology, which measures the topology, morphology, and travel group strategies of cancer cells; and RP3 Dynomics, which characterizes the genomics and transcriptomics of cancer cells. With assessment of depth, breadth, and fidelity thus assured, the measurements will be empowerd by analyses of other parameters, including standard pathologic and clinical patient information. This extensive amalgamation of data, based primarily on physics investigations and mathematical theory, but informed by strategic patient sampling and clinical information, will be processed by advanced statistical analysis and mathematical modeling, to enable a highly predictive simulation of cancer spread that will revolutionize our understanding of metastasis. The 4DB Center will also serve to disseminate information, education, and training to a new generation of cancer physicists; a generation that will implement the power of physics to conquer the problems of cancer.

通过血流的癌症转移可以被建模为与多个细胞的流体-固体相互作用的问题。 不同质量、动量和物理性质的物体（细胞）在复杂流场中运动。 四维活检中心（4DB）利用基于物理的测量、数学建模 和数值模拟，以经验性地表征实际的人类癌症患者样本，目标是 建立一个高度预测人类癌细胞行为的模型，这将从根本上改变我们目前的 了解癌症转移的机制。广泛的实证测量和分析 将在来自人类癌症患者的一组连贯样本上进行。样本将由细胞组成 原发性肿瘤、局部转移灶和循环肿瘤细胞（CTC）随时间的变化， 同一个病人。另外，第二组样品将由来自大组的CTC组成。 患者，按肿瘤类型和癌症分期分层。这些样本集将由三个平行分析 独立的研究项目（RP），产生相同现象的正交措施，以及 提供上皮癌的空间和时间维度上的变量和相关性。的 三个研究项目（RP）是：RP 1细胞物理学，它确定了物理和机械 癌细胞的特性; RP 2拓扑，测量拓扑、形态和旅行组 RP 3 Dynomics，它描述了癌细胞的基因组学和转录组学， 癌细胞随着深度，广度和保真度的评估，因此保证，测量将 通过分析其他参数，包括标准的病理和临床患者信息。 这种广泛的数据融合，主要基于物理学研究和数学理论，但 根据战略性患者采样和临床信息，将通过高级统计学 分析和数学建模，以实现对癌症扩散的高度预测性模拟， 彻底改变了我们对转移的理解4DB中心还将用于传播信息， 教育和培训新一代的癌症物理学家;一代人将实施权力 攻克癌症难题的物理学。