CDS&E: Mathematical Models and Computational Methods for the Tumor Microenvironment

CDS

• 批准号: 1317671
• 负责人: Robert Dillon
• 金额: $ 38.09万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1317671&HistoricalAwards=false
• 关键词: CDS&E; Mathematical; Models; Computational; Methods

The main objective of this work is to develop comprehensive mathematical models and computational methods at the microscale for the emergence of ductal carcinoma in situ (DCIS) and the transition to invasive ductal carcinoma (IDC) both in vivo and in vitro microfluidic devices. The investigator and his colleagues develop computational methods for the microenvironment models based on integrated second-order finite volume methods for each of the system components - fluid mechanics, chemical and ion transport in the bulk fluid, reactions on the cell membrane, transport through the cell membrane, and fluid/structure interaction of the elastic biological cells. The modeling innovation includes the incorporation of ion transport, reaction, and diffusion in a cells-based model with detailed membrane reaction kinetics and membrane transport. This is coupled with internal kinetics and growth processes of individual cells. Another innovation is the incorporation of Lagrangian mesh based models for the viscoelastic properties of matrigel and extracellular matrix.Breast cancer is the second-leading cause of death in women in developed countries. In USA alone, 230,480 women were diagnosed with invasive breast cancer in 2011 and an estimated 57,650 women were tested positive with non invasive ductal carcinoma (DCIS). Although DCIS itself is not life-threatening, it has a high probability of progression to IDC if left untreated. In this project, the investigator and his colleagues study tumor microenvironments in DCIS and its progression to IDC. Successful completion of this project provides a fundamental change in modeling of tumor evolution where the identity of each cell is of importance. Although focus has been placed on modeling ductal carcinoma, one can extend these techniques to the study of variety of biological processes. A number of research fields are benefited from this work. These include cell biology, systems biology, biomedical engineering, computational fluid mechanics, and applied and computational mathematics. In addition to this technical impact, the project provides a unique educational opportunity to train graduate and undergraduate students as well as high school teachers in multidisciplinary environments.

这项工作的主要目标是在微尺度上为导管原位癌（DCIS）的出现以及在体内和体外微流控装置中向浸润性导管癌（IDC）的转变开发全面的数学模型和计算方法。研究人员和他的同事们开发了基于集成二阶有限体积法的微环境模型的计算方法，用于每个系统组件-流体力学，散装流体中的化学和离子运输，细胞膜上的反应，通过细胞膜的运输，以及弹性生物细胞的流体/结构相互作用。建模创新包括将离子传输，反应和扩散在一个基于细胞的模型与详细的膜反应动力学和膜传输。这与单个细胞的内部动力学和生长过程相结合。另一个创新是结合拉格朗日网格为基础的模型的粘弹性的matrigel和细胞外基质。乳腺癌是第二大死因的妇女在发达国家。仅在美国，2011年就有230，480名女性被诊断患有浸润性乳腺癌，估计有57，650名女性被检测为非浸润性导管癌（DCIS）阳性。虽然DCIS本身不会危及生命，但如果不治疗，它很有可能进展为IDC。在这个项目中，研究人员和他的同事研究了DCIS中的肿瘤微环境及其向IDC的进展。该项目的成功完成为肿瘤演变的建模提供了根本性的变化，其中每个细胞的身份非常重要。虽然重点放在导管癌的建模，人们可以扩展这些技术的各种生物过程的研究。许多研究领域都受益于这项工作。这些学科包括细胞生物学、系统生物学、生物医学工程、计算流体力学以及应用和计算数学。 除了这种技术影响，该项目提供了一个独特的教育机会，培养研究生和本科生以及高中教师在多学科环境。