Multiscale Mathematical Modeling of Cancer Invasion

癌症侵袭的多尺度数学模型

• 批准号: 7926030
• 负责人: Vito Quaranta
• 金额: $ 24.8万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7926030
• 关键词: Adhesions; Apoptosis; Cell Culture System; Cell Proliferation; Cells; Computer Simulation; Computer software; Data; Diagnostic; Encapsulated; Extracellular Matrix; Genetic; Goals; Hybrids; Inflammation; Knowledge; Link; Malignant Neoplasms; Measurement; Metabolism; Modeling; Mutation; Nature; Neoplasm Metastasis; Peptide Hydrolases; Process; Research Personnel; Staging; Tissues; Validation; Xenograft procedure; angiogenesis; base; cancer cell; human cancer mouse model; improved; in vitro testing; in vivo; mathematical model; migration; molecular scale; programs; simulation; therapeutic target; tool; tumor progression; two-dimensional

DESCRIPTION (provided by applicant): The goal of this cross-disciplinary project is to produce mathematical models and simulation software that describe quantitatively the process of cancer invasion and encapsulate the knowledge derived from a wide range of experimental observations into a correlative and predictive tool, available to all researchers. Cancer invasion is thought to involve a number of cellular parameters (including altered rates of cell proliferation, apoptosis, migration, adhesion, metabolism, and mutation), as well as microenvironmental parameters (including extracellular matrix composition, angiogenesis, inflammation, and proteases). From a mathematical point of view, some of these parameters are continuous and some discrete. Therefore, our primary approach is based on a hybrid model in which both continuum deterministic and discrete stochastic parameters and variables are integrated. Because of its hybrid nature, the model can be directly linked to experimental measurements of those cellular and microenvironmental parameters recognized by cancer biologists as important in cancer invasion. Predictions based on the hybrid models will be visualized by software that implements computer simulations of invasion. These models and the associated simulations will be the basis for generating hypotheses that will be tested in vitro, in two-dimensional (2D) and three-dimensional (3D) cancer cell culture systems, as well as in vivo, in xenograft and genetic mouse models for human cancers. Experimental validation will be used to both refine and improve the mathematical models and simulation programs in an iterative fashion and provide new input parameters for the models. Initially, we will model invasion parameters at a level of complexity that does not hinder mathematical and experimental feasibility, but that already provides a realistic representation of cancer invasion. As we progress, we will be able to introduce increasing levels of complexity, since the model is open to incorporation of parameters and experimental data from several scales, e.g., the macro-scale (tissue), micro-scale (cells), subcellular, and molecular scales. The long-term goal is to produce a comprehensive, quantitative description of the major mechanisms underlying cancer invasion. This description, and the associated computer simulations, should enable a rational approach for accurate diagnostic staging and therapeutic targeting of the invasion/metastasis step of cancer progression.

描述（由申请人提供）：这个跨学科项目的目标是生成数学模型和仿真软件，这些模型和仿真软件可以定量地描述癌症入侵的过程，并封装了从广泛的实验观察结果中得出的知识，这些知识可用于所有研究人员使用的相关和预测工具。癌症侵袭被认为涉及许多细胞参数（包括细胞增殖率改变，凋亡，迁移，粘附，代谢和突变）以及微环境参数（包括细胞外基质组成，血管生成，炎症和蛋白酶）。从数学的角度来看，其中一些参数是连续的，有些是离散的。因此，我们的主要方法是基于混合模型，在该模型中，连续性确定性和离散的随机参数和变量都集成在一起。由于其杂种性质，该模型可以直接与癌症生物学家识别为癌症入侵重要的那些细胞和微环境参数的实验测量。基于混合模型的预测将通过实现计算机模拟入侵的软件可视化。这些模型和相关的模拟将是生成将在体外，二维（2D）和三维（3D）癌细胞培养系统以及体内，在异种移植物和遗传小鼠模型中进行体外测试的假设的基础。实验验证将以迭代方式来完善和改进数学模型和仿真程序，并为模型提供新的输入参数。最初，我们将在不阻碍数学和实验性可行性的复杂性水平上对入侵参数进行建模，但已经提供了癌症侵袭的现实表示。随着我们的进展，我们将能够引入越来越多的复杂性水平，因为该模型开放，可以从多个尺度（例如宏观尺度（组织），微尺度（细胞），亚细胞和分子尺度纳入参数和实验数据。长期目标是对癌症入侵的主要机制进行全面的定量描述。该描述以及相关的计算机模拟应为癌症进展的入侵/转移步骤的准确诊断分期和治疗靶向提供合理的方法。