论文标题

治疗引起的肿瘤聚集体的收缩:一种非线性填充趋化方法

Treatment-induced shrinking of tumour aggregates: A nonlinear volume-filling chemotactic approach

论文作者

Almeida, Luis, Estrada-Rodriguez, Gissell, Oliver, Lisa, Peurichard, Diane, Poulain, Alexandre, Vallette, Francois

论文摘要

由源自胶质母细胞瘤的3D/器官培养物的实验观察结果,我们开发了一个数学模型,其中由于营养受限的细胞增殖与基于趋化性的细胞运动相结合,因此获得了肿瘤聚集体的形成。化学治疗的引入引起细胞水平的机械变化,并且细胞经历了从刚体到半弹性实体的过渡。我们通过引入偏微分方程的非线性填充趋化趋化系统,分析了这些单个机械变化对在人群水平上获得的骨料性质的影响。通过所谓的挤压概率考虑了细胞的弹性特性,这使我们能够根据细胞外微环境中的治疗浓度来改变聚集体的填料能力。我们探索了治疗作用的两种情况:首先,治疗仅作用于细胞的机械性能,其次,我们假设它也可以防止细胞增殖。线性稳定性分析使我们能够研究系统创建模式的能力。我们在1D和2D中提供数值模拟,以说明由于存在治疗而导致聚集体的收缩。

Motivated by experimental observations in 3D/organoid cultures derived from glioblastoma, we develop a mathematical model where tumour aggregate formation is obtained as the result of nutrient-limited cell proliferation coupled with chemotaxis-based cell movement. The introduction of a chemotherapeutic treatment induces mechanical changes at the cell level, with cells undergoing a transition from rigid bodies to semi-elastic entities. We analyse the influence of these individual mechanical changes on the properties of the aggregates obtained at the population level by introducing a nonlinear volume-filling chemotactic system of partial differential equations. The elastic properties of the cells are taken into account through the so-called squeezing probability, which allows us to change the packing capacity of the aggregates, depending on the concentration of the treatment in the extracellular microenvironment. We explore two scenarios for the effect of the treatment: firstly, the treatment acts only on the mechanical properties of the cells and, secondly, we assume it also prevents cell proliferation. A linear stability analysis enables us to study the ability of the system to create patterns. We provide numerical simulations in 1D and 2D that illustrate the shrinking of the aggregates due to the presence of the treatment.

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