论文标题
神经胶质瘤伪层的多尺度建模：肿瘤微环境的贡献
Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment
论文作者
论文摘要
神经胶质瘤是原发性脑肿瘤，具有高侵入性和渗透性扩散。其中，胶质母细胞瘤多形（GBM）表现出微血管增生，并由缺氧触发明显的坏死。围绕毛细血管遮挡部位的花环样高细胞结构（所谓的伪层）的组织学样本是GBM的典型特征，并暗示了患者生存的预后不良。我们在活动粒子框架的动力学理论中提出了一种多尺度建模方法，并通过升级过程推断出具有驱虫pH及性的反应扩散模型。我们证明了为获得的宏观系统的版本而存在独特的全局有限的经典解决方案，并研究了解决方案的渐近行为。此外，我们研究了两种不同类型的缩放，并通过模拟进行了比较所获得的宏观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1（包括伪层）。当PDE通过抛物线缩放（无向组织）获得时，这是正确的，而没有观察到由双曲线极限（定向组织）引起的PDE的模式。这表明脑组织可能是无方向性的 - 至少就神经胶质瘤的迁移而言。我们还研究了两种不同的方法，包括对缺氧反应及其相关方式的细胞水平描述。
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 patterns1 (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.
