研究动态
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芯片肿瘤装置中癌症坏死核心形成的计算模型。

Computational model of the cancer necrotic core formation in a tumor-on-a-chip device.

发表日期:2024 Jun 27
作者: Elton Diêgo Bonifácio, Cleudmar Amaral Araújo, Marcília Valéria Guimarães, Márcio Peres de Souza, Thiago Parente Lima, Bethânia Alves de Avelar Freitas, Libardo Andrés González Torres
来源: Cell Death & Disease

摘要:

无血管肿瘤内坏死区域形成的机制很复杂且知之甚少。在本文中,我们研究了微流体装置内 3D 肿瘤细胞培养物中坏死核心的形成,并通过计算数学模型考虑了氧气、营养物质和微环境酸化。我们的目标是根据微环境条件模拟细胞过程,包括微流体装置内的增殖和死亡。我们采用有限元模型进行近似,考虑了葡萄糖、氧和氢离子的扩散、消耗和产生,以及细胞增殖、迁移和死亡,解决了肿瘤细胞在不同条件下如何进化的问题。所得到的数学模型在不同的场景下进行了检验,能够再现不同细胞浓度下的细胞死亡和增殖,以及坏死核心的形成,与文献报道的实验数据非常吻合。这种方法不仅增进了我们对坏死核心形成的基本理解,而且还提供了一个强大的计算平台来研究个性化治疗策略,为癌症研究和治疗设计提供了重要工具。版权所有 © 2024 Elsevier Ltd. 保留所有权利。
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing the finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.Copyright © 2024 Elsevier Ltd. All rights reserved.