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基于主体和连续统模型的溶瘤病毒感染的空间动力学。

Agent-Based and Continuum Models for Spatial Dynamics of Infection by Oncolytic Viruses.

机构信息

Department of Mathematical Sciences "G. L. Lagrange", Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129, Turin, Italy.

Department of Mathematics, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, John St, Hawthorn, VIC, 3122, Australia.

出版信息

Bull Math Biol. 2023 Aug 31;85(10):92. doi: 10.1007/s11538-023-01192-x.

DOI:10.1007/s11538-023-01192-x
PMID:37653164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10471645/
Abstract

The use of oncolytic viruses as cancer treatment has received considerable attention in recent years, however the spatial dynamics of this viral infection is still poorly understood. We present here a stochastic agent-based model describing infected and uninfected cells for solid tumours, which interact with viruses in the absence of an immune response. Two kinds of movement, namely undirected random and pressure-driven movements, are considered: the continuum limit of the models is derived and a systematic comparison between the systems of partial differential equations and the individual-based model, in one and two dimensions, is carried out. In the case of undirected movement, a good agreement between agent-based simulations and the numerical and well-known analytical results for the continuum model is possible. For pressure-driven motion, instead, we observe a wide parameter range in which the infection of the agents remains confined to the center of the tumour, even though the continuum model shows traveling waves of infection; outcomes appear to be more sensitive to stochasticity and uninfected regions appear harder to invade, giving rise to irregular, unpredictable growth patterns. Our results show that the presence of spatial constraints in tumours' microenvironments limiting free expansion has a very significant impact on virotherapy. Outcomes for these tumours suggest a notable increase in variability. All these aspects can have important effects when designing individually tailored therapies where virotherapy is included.

摘要

近年来,溶瘤病毒作为癌症治疗方法受到了广泛关注,但其感染的空间动力学仍知之甚少。本文提出了一个描述固体肿瘤中感染和未感染细胞的随机主体模型,该模型在没有免疫反应的情况下与病毒相互作用。考虑了两种运动方式,即无定向随机运动和压力驱动运动:推导出模型的连续体极限,并在一维和二维情况下对偏微分方程组和基于个体的模型进行了系统比较。在无定向运动的情况下,基于主体的模拟与连续体模型的数值和众所周知的解析结果之间可以很好地达成一致。然而,对于压力驱动运动,我们观察到一个很宽的参数范围,其中感染剂仍然局限于肿瘤的中心,尽管连续体模型显示出感染的传播波;结果似乎对随机性更敏感,未感染区域更难以侵入,导致不规则、不可预测的生长模式。我们的研究结果表明,肿瘤微环境中存在限制自由扩张的空间限制对病毒疗法有非常显著的影响。这些肿瘤的结果表明可变性显著增加。在设计包括病毒疗法的个体化治疗方案时,所有这些方面都可能产生重要影响。

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