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溶瘤病毒治疗中具有溶周期延迟的空间模型。

Spatial Model for Oncolytic Virotherapy with Lytic Cycle Delay.

机构信息

Department of Mathematical Sciences, New Mexico State University, Las Cruces, NM, 88001, USA.

School of Mathematical Sciences, Heilongjiang University, Harbin, 150080, Heilongjiang, People's Republic of China.

出版信息

Bull Math Biol. 2019 Jul;81(7):2396-2427. doi: 10.1007/s11538-019-00611-2. Epub 2019 May 14.

Abstract

We formulate a mathematical model of functional partial differential equations for oncolytic virotherapy which incorporates virus diffusivity, tumor cell diffusion, and the viral lytic cycle based on a basic oncolytic virus dynamics model. We conduct a detailed analysis for the dynamics of the model and carry out numerical simulations to demonstrate our analytic results. Particularly, we establish the positive invariant domain for the [Formula: see text] limit set of the system and show that the model has three spatially homogenous equilibriums solutions. We prove that the spatially uniform virus-free steady state is globally asymptotically stable for any viral lytic period delay and diffusion coefficients of tumor cells and viruses when the viral burst size is smaller than a critical value. We obtain the conditions, for example the ratio of virus diffusion coefficient to that of tumor cells is greater than a value and the viral lytic cycle, is greater than a critical value, under which the spatially uniform positive steady state is locally asymptotically stable. We also obtain conditions under which the system undergoes Hopf bifurcations, and stable periodic solutions occur. We point out medical implications of our results which are difficult to obtain from models without combining diffusive properties of viruses and tumor cells with viral lytic cycles.

摘要

我们基于基本的溶瘤病毒动力学模型,针对溶瘤病毒治疗建立了一个功能性偏微分方程的数学模型,其中包含病毒扩散率、肿瘤细胞扩散率和病毒裂解周期。我们对模型的动力学进行了详细分析,并进行了数值模拟以验证我们的分析结果。特别地,我们建立了系统的 [Formula: see text] 极限集的正不变域,并证明了该模型有三个空间均匀平衡点。我们证明,当病毒爆发大小小于一个临界值时,对于任何病毒裂解周期延迟和肿瘤细胞和病毒的扩散系数,无病毒的空间均匀稳定状态是全局渐近稳定的。我们得到了一些条件,例如病毒扩散系数与肿瘤细胞扩散系数的比值大于一个值,以及病毒裂解周期大于一个临界值,在此条件下,空间均匀正稳定状态是局部渐近稳定的。我们还得到了系统发生 Hopf 分支和出现稳定周期解的条件。我们指出了我们的结果的医学意义,这些意义是难以从不将病毒和肿瘤细胞的扩散特性与病毒裂解周期相结合的模型中获得的。

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