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Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment
Journal of Mathematical Biology ( IF 1.9 ) Pub Date : 2021-04-12 , DOI: 10.1007/s00285-021-01599-x
Pawan Kumar 1 , Jing Li 2 , Christina Surulescu 1
Affiliation  

Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns (not necessarily of Turing type), including pseudopalisades, can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related .



中文翻译:

胶质瘤假栅栏的多尺度建模:来自肿瘤微环境的贡献

胶质瘤是具有高侵袭潜力和浸润性扩散的原发性脑肿瘤。其中,多形性胶质母细胞瘤(GBM)表现出微血管增生和缺氧引发的明显坏死。组织学样本显示以毛细血管闭塞位点为中心的花环样多细胞结构(所谓的假栅栏)是 GBM 的典型特征,并暗示患者生存的不良预后。我们在活性粒子框架的动力学理论中提出了一种多尺度建模方法,并通过放大过程推导出具有排斥性 pH 趋向性的反应扩散模型。我们证明了所获得的宏观系统版本的唯一全局有界经典解的存在,并研究了该解的渐近行为。而且,我们研究了两种不同类型的缩放,并通过模拟比较了获得的宏观 PDE 的行为。这些表明,根据肿瘤等级,可以为某些参数范围形成模式(不一定是图灵类型),包括假栅栏。当通过抛物线缩放(无向组织)获得 PDE 时,这是正确的,而对于由双曲线极限(有向组织)产生的 PDE,则没有观察到这种模式。这表明脑组织可能是无方向的——至少就胶质瘤迁移而言。我们还研究了两种不同的方法,包括对缺氧反应的细胞水平描述及其相关方式。可以根据肿瘤等级形成一些参数范围。当通过抛物线缩放(无向组织)获得 PDE 时,这是正确的,而对于由双曲线极限(有向组织)产生的 PDE,则没有观察到这种模式。这表明脑组织可能是无方向的——至少就胶质瘤迁移而言。我们还研究了两种不同的方法,包括对缺氧反应的细胞水平描述及其相关方式。可以根据肿瘤等级形成一些参数范围。当通过抛物线缩放(无向组织)获得 PDE 时,这是正确的,而对于由双曲线极限(有向组织)产生的 PDE,则没有观察到这种模式。这表明脑组织可能是无方向的——至少就胶质瘤迁移而言。我们还研究了两种不同的方法,包括对缺氧反应的细胞水平描述及其相关方式。

更新日期:2021-04-13
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