Amereh Meitham, Edwards Roderick, Akbari Mohsen, Nadler Ben
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8W 2Y2, Canada.
Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, Victoria, BC V8W 2Y2, Canada.
Micromachines (Basel). 2021 Jun 25;12(7):749. doi: 10.3390/mi12070749.
Mathematical modeling has significant potential for understanding of biological models of cancer and to accelerate the progress in cross-disciplinary approaches of cancer treatment. In mathematical biology, solid tumor spheroids are often studied as preliminary models of avascular tumors. The size of spheroids and their cell number are easy to track, making them a simple model to investigate tumor behavior, quantitatively. The growth of solid tumors is comprised of three main stages: transient formation, monotonic growth and a plateau phase. The last two stages are extensively studied. However, the initial transient formation phase is typically missing from the literature. This stage is important in the early dynamics of growth, formation of clonal sub-populations, etc. In the current work, this transient formation is modeled by a reaction-diffusion partial differential equation (PDE) for cell concentration, coupled with an ordinary differential equation (ODE) for the spheroid radius. Analytical and numerical solutions of the coupled equations were obtained for the change in the radius of tumor spheroids over time. Human glioblastoma (hGB) cancer cells (U251 and U87) were spheroid cultured to validate the model prediction. Results of this study provide insight into the mechanism of development of solid tumors at their early stage of formation.
数学建模在理解癌症生物学模型以及加速癌症治疗跨学科方法的进展方面具有巨大潜力。在数学生物学中,实体瘤球体常被作为无血管肿瘤的初步模型进行研究。球体的大小及其细胞数量易于追踪,这使其成为定量研究肿瘤行为的简单模型。实体瘤的生长包括三个主要阶段:短暂形成期、单调生长期和平台期。后两个阶段已得到广泛研究。然而,文献中通常缺少初始的短暂形成期。这个阶段在生长的早期动态、克隆亚群的形成等方面很重要。在当前工作中,这种短暂形成过程通过一个关于细胞浓度的反应扩散偏微分方程(PDE)以及一个关于球体半径的常微分方程(ODE)进行建模。针对肿瘤球体半径随时间的变化,获得了耦合方程的解析解和数值解。对人胶质母细胞瘤(hGB)癌细胞(U251和U87)进行球体培养以验证模型预测。本研究结果为实体瘤形成早期阶段的发展机制提供了见解。
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