Welter Michael, Rieger Heiko
Theoretical Physics, Saarland University, Campus E2 6, 66123, Saarbrücken, Germany.
Adv Exp Med Biol. 2016;936:31-72. doi: 10.1007/978-3-319-42023-3_3.
Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.
肿瘤血管系统是为生长中的肿瘤提供氧气或葡萄糖等营养物质的血管网络，在许多方面与正常组织中分层组织的动静脉血管网络不同。血管生成（新血管的形成）、血管共选（现有血管融入肿瘤血管系统）和血管消退将健康的血管网络重塑为肿瘤特异性血管系统。基于详细实验数据和物理定律的整合模型在计算机上实现了分子途径、细胞增殖、迁移和死亡、组织微环境、机械和流体动力以及宿主组织血管系统精细结构之间的复杂相互作用。借助计算机模拟，可以获得有关血流模式、间质液流动、药物分布、氧气和营养物质分布的高精度信息，并且可以在临床试验之前测试大量治疗方案。本章概述了肿瘤生长过程中血管重塑的计算机模拟现状，包括肿瘤内的间质液流动、药物递送和氧气供应。将模型预测与实验和临床数据进行比较，并对一些关于肿瘤血管系统和肿瘤内溶质运输的长期生理范式进行严格审查。
