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: 8539308
• 负责人: PETER KUHN
• 金额: $ 185.45万
• 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 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8539308
• 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 Circulating Cells; 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; empowered; mathematical model; mathematical theory; 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 empowered 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在复杂流场内与运动中的不同质量、动量和物理性质的多个主体（细胞）的流体-固体相互作用的问题。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来经验性地表征实际的人类癌症患者样本，其目标是建立人类癌细胞行为的高度预测模型，这将从根本上改变我们目前对癌症转移机制的理解。将对来自人类癌症患者的一组连贯样本进行广泛的经验测量和分析。样本将由来自原发性肿瘤、局部转移瘤和循环肿瘤细胞（CTC）的细胞组成，所有细胞均采集自同一患者。此外，第二组样品将由来自一大组患者的CTC组成，按肿瘤类型和癌症阶段分层。这些样本集将由三个独立的研究项目（RP）并行分析，产生相同现象的正交测量，并提供变量和上皮癌的空间和时间维度的相关性。三个研究项目（RP）是：RP 1细胞物理学，它确定了癌细胞的物理和机械特性; RP 2拓扑学，它测量了癌细胞的拓扑结构，形态和旅行组策略;和RP 3动力学，它表征了癌细胞的基因组学和转录组学。随着深度、广度和保真度的评估得到保证，测量将通过分析其他参数（包括标准病理学和临床患者信息）来增强。这种广泛的数据融合，主要基于物理学研究和数学理论，但由战略性患者采样和临床信息提供信息，将通过先进的统计分析和数学建模进行处理，以实现对癌症扩散的高度预测性模拟，这将彻底改变我们对转移的理解。4DB中心还将为新一代癌症物理学家传播信息，教育和培训;这一代人将利用物理学的力量来征服癌症问题。