Novozhilov Artem S, Berezovskaya Faina S, Koonin Eugene V, Karev Georgy P
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Biol Direct. 2006 Feb 17;1:6. doi: 10.1186/1745-6150-1-6.
Oncolytic viruses that specifically target tumor cells are promising anti-cancer therapeutic agents. The interaction between an oncolytic virus and tumor cells is amenable to mathematical modeling using adaptations of techniques employed previously for modeling other types of virus-cell interaction.
A complete parametric analysis of dynamic regimes of a conceptual model of anti-tumor virus therapy is presented. The role and limitations of mass-action kinetics are discussed. A functional response, which is a function of the ratio of uninfected to infected tumor cells, is proposed to describe the spread of the virus infection in the tumor. One of the main mathematical features of ratio-dependent models is that the origin is a complicated equilibrium point whose characteristics determine the main properties of the model. It is shown that, in a certain area of parameter values, the trajectories of the model form a family of homoclinics to the origin (so-called elliptic sector). Biologically, this means that both infected and uninfected tumor cells can be eliminated with time, and complete recovery is possible as a result of the virus therapy within the framework of deterministic models.
Our model, in contrast to the previously published models of oncolytic virus-tumor interaction, exhibits all possible outcomes of oncolytic virus infection, i.e., no effect on the tumor, stabilization or reduction of the tumor load, and complete elimination of the tumor. The parameter values that result in tumor elimination, which is, obviously, the desired outcome, are compatible with some of the available experimental data.
This article was reviewed by Mikhail Blagosklonny, David Krakauer, Erik Van Nimwegen, and Ned Wingreen.
Reviewed by Mikhail Blagosklonny, David Krakauer, Erik Van Nimwegen, and Ned Wingreen. For the full reviews, please go to the Reviewers' comments section.
特异性靶向肿瘤细胞的溶瘤病毒是很有前景的抗癌治疗药物。溶瘤病毒与肿瘤细胞之间的相互作用适合采用先前用于模拟其他类型病毒-细胞相互作用的技术进行数学建模。
本文给出了抗肿瘤病毒治疗概念模型动态机制的完整参数分析。讨论了质量作用动力学的作用和局限性。提出了一种功能反应，它是未感染肿瘤细胞与感染肿瘤细胞比例的函数，用于描述病毒感染在肿瘤中的传播。比率依赖模型的一个主要数学特征是原点是一个复杂的平衡点，其特性决定了模型的主要性质。结果表明，在一定的参数值区域内，模型的轨迹形成一族到原点的同宿轨道（所谓的椭圆扇形）。从生物学角度来看，这意味着随着时间的推移，感染和未感染的肿瘤细胞都可以被清除，并且在确定性模型的框架内，病毒治疗有可能实现完全恢复。
与先前发表的溶瘤病毒-肿瘤相互作用模型不同，我们的模型展示了溶瘤病毒感染的所有可能结果，即对肿瘤无影响、肿瘤负荷稳定或降低以及肿瘤完全消除。导致肿瘤消除（显然这是期望的结果）的参数值与一些现有实验数据相符。
本文由米哈伊尔·布拉戈克隆尼、大卫·克拉考尔、埃里克·范·尼姆韦根和内德·温格林评审。
由米哈伊尔·布拉戈克隆尼、大卫·克拉考尔、埃里克·范·尼姆韦根和内德·温格林评审。如需完整评审，请前往评审人评论部分。
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