Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: Clinical implications and therapeutic targeting strategies
Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: Clinical implications and therapeutic targeting strategies
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DOI：
10.1016/j.jtbi.2005.12.022
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发表时间：
2006-08-07
影响因子：
2
通讯作者：
Chaplain, Mark A. J.
中科院分区：
文献类型：
--
作者：
McDougall, Steven R.;Anderson, Alexander R. A.;Chaplain, Mark A. J.
血管生成，即血管网络的生长，是实体瘤生长的关键组成部分，将相对无害的无血管生长阶段和潜在致命的血管生长阶段联系起来。作为一个过程，血管生成是一系列精心安排的事件，涉及内皮细胞迁移、增殖;组织降解;新毛细血管（萌芽）形成;环形成（吻合），以及至关重要的是，血液流过网络。一旦存在与新生网络相关联的血流，网络的后续生长响应于血管生成因子、经由细胞外基质的迁移线索和灌注相关的血液动力学力的组合效应而在时间和空间上以可以被描述为适应性和动态的方式演变。在本文中，我们提出了一个数学模型，同时耦合血管生长和血液流动通过血管-动态自适应肿瘤诱导血管生成（DATIA）。这个新的数学模型提出了一个理论和计算调查的过程，并强调了一些重要的新目标的治疗干预。与早期的流动模型相比，其中灌注（血流）的影响基本上是后验评估的，即在生成中空网络之后，本文所述的模型中的血流在毛细血管生长期间具有直接影响，其中径向适应和网络重塑作为原发性血管病变的直接后果而发生。毛细血管网络架构产生的动态自适应模型被发现从根本上不同，从那些使用早期models.The DATIA模型是用来检查改变各种物理和生物模型参数的影响，发展中的血管结构和化疗药物的输送到肿瘤。随后的模拟化疗治疗不同的参数制度下，导致确定了一些新的治疗靶点的肿瘤管理。(c)2006爱思唯尔有限公司保留所有权利。
Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumour growth, linking the relatively harmless avascular growth phase and the potentially fatal vascular growth phase. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration, proliferation; degradation of tissue; new capillary vessel (sprout) formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is blood flow associated with the nascent network, the subsequent growth of the network evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix and perfusion-related haemodynamic forces in a manner that may be described as both adaptive and dynamic. In this paper we present a mathematical model which simultaneously couples vessel growth with blood flow through the vessels-dynamic adaptive tumour-induced angiogenesis (DATIA). This new mathematical model presents a theoretical and computational investigation of the process and highlights a number of important new targets for therapeutic intervention. In contrast to earlier flow models, where the effects of perfusion (blood flow) were essentially evaluated a posteriori, i.e. after generating a hollow network, blood flow in the model described in this paper has a direct impact during capillary growth, with radial adaptations and network remodelling occurring as immediate consequences of primary anastomoses. Capillary network architectures resulting from the dynamically adaptive model are found to differ radically from those obtained using earlier models.The DATIA model is used to examine the effects of changing various physical and biological model parameters on the developing vascular architecture and the delivery of chemotherapeutic drugs to the tumour. Subsequent simulations of chemotherapeutic treatments under different parameter regimes lead to the identification of a number of new therapeutic targets for tumour management. (c) 2006 Elsevier Ltd. All rights reserved.