Coupled modelling of tumour angiogenesis, tumour growth and blood perfusion
Coupled modelling of tumour angiogenesis, tumour growth and blood perfusion
复制标题
DOI：
10.1016/j.jtbi.2011.02.017
复制
发表时间：
2011-06-21
影响因子：
2
通讯作者：
Long, Quan
中科院分区：
文献类型：
--
作者：
Cai, Yan;Xu, Shixiong;Long, Quan
我们提出了一个数学模型系统，通过充分耦合血管生长，肿瘤生长和血液灌注来研究肿瘤细胞增殖，死亡和肿瘤血管生成的动态过程。肿瘤生长和血管生成通过化学微环境和细胞-基质相互作用耦合。在更新的脉管系统上进行血液动力学计算。模型中耦合了血管内、跨毛细血管和间质液流，以提供血液灌注变量的综合解决方案。根据壁剪切应力标准进行血管塌陷的估计，以提供关于血管重塑的反馈。模拟可以显示肿瘤血管生成的过程和肿瘤细胞的空间分布，时间长达24天。它可以显示在此期间肿瘤和肿瘤微血管系统的主要特征，例如在肿瘤中心形成大的坏死核心，很少有功能性血管通过，以及循环良好的肿瘤周边区域，其中微血管密度高，并且与生长肿瘤的更具侵略性的增殖细胞相关，这些都与生理学观察结果一致。研究还表明，仿真结果不依赖于初始肿瘤和网络，这进一步证实了耦合模型反馈机制的应用。该模型使我们能够检查血管生成和肿瘤生长之间的相互作用，并研究实体肿瘤对微环境变化的动态响应。这种模拟框架可以为进一步的应用，如药物输送和抗血管生成治疗的基础。皇冠版权所有（C）2011由爱思唯尔有限公司出版。保留所有权利。
We propose a mathematical modelling system to investigate the dynamic process of tumour cell proliferation, death and tumour angiogenesis by fully coupling the vessel growth, tumour growth and blood perfusion. Tumour growth and angiogenesis are coupled by the chemical microenvironment and the cell-matrix interaction. The haemodynamic calculation is carried out on the updated vasculature. The domains of intravascular, transcapillary and interstitial fluid flow were coupled in the model to provide a comprehensive solution of blood perfusion variables. An estimation of vessel collapse is made according to the wall shear stress criterion to provide feedback on vasculature remodelling. The simulation can show the process of tumour angiogenesis and the spatial distribution of tumour cells for periods of up to 24 days. It can show the major features of tumour and tumour microvasculature during the period such as the formation of a large necrotic core in the tumour centre with few functional vessels passing through, and a well circulated tumour periphery regions in which the microvascular density is high and associated with more aggressive proliferating cells of the growing tumour which are all consistent with physiological observations. The study also demonstrated that the simulation results are not dependent on the initial tumour and networks, which further confirms the application of the coupled model feedback mechanisms. The model enables us to examine the interactions between angiogenesis and tumour growth, and to study the dynamic response of a solid tumour to the changes in the microenvironment. This simulation framework can be a foundation for further applications such as drug delivery and anti-angiogenic therapies. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.