Mathematical modeling of tumor therapy with oncolytic viruses: regimes with complete tumor elimination within the framework of deterministic models.
Mathematical modeling of tumor therapy with oncolytic viruses: regimes with complete tumor elimination within the framework of deterministic models.
复制标题
DOI：
10.1186/1745-6150-1-6
复制
发表时间：
2006-02-17
期刊：
影响因子：
5.5
通讯作者：
Karev GP
中科院分区：
文献类型：
--
作者：
Novozhilov AS;Berezovskaya FS;Koonin EV;Karev GP
特异性靶向肿瘤细胞的溶瘤病毒是有前途的抗癌治疗剂。溶瘤病毒和肿瘤细胞之间的相互作用适用于使用先前用于建模其他类型的病毒-细胞相互作用的技术的适应的数学建模。提出了一个完整的抗肿瘤病毒治疗的概念模型的动态机制的参数分析。质量作用动力学的作用和局限性进行了讨论。提出了一种功能反应，它是未感染的肿瘤细胞与感染的肿瘤细胞的比率的函数，以描述病毒感染在肿瘤中的传播。比率依赖模型的主要数学特征之一是原点是一个复杂的平衡点，其特征决定了模型的主要性质。它表明，在一定的区域内的参数值，该模型的轨迹形成一个家庭的同宿原点（所谓的椭圆扇区）。在生物学上，这意味着感染和未感染的肿瘤细胞都可以随着时间的推移而被消除，并且由于在确定性模型的框架内的病毒治疗，完全恢复是可能的。我们的模型，与先前发表的溶瘤病毒-肿瘤相互作用的模型相反，展示了溶瘤病毒感染的所有可能结果，即，对肿瘤无影响，稳定或减少肿瘤负荷，并完全消除肿瘤。导致肿瘤消除的参数值，这显然是期望的结果，与一些可用的实验数据是相容的。本文由Mikhail Blagosklonny、大卫Krakauer、Erik货车Nimwegen和Ned Wingreen审阅。
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.
登录
查看更多内容
影响因子：
1.9
作者：
Berezovskaya, F;Karev, G;Arditi, R
通讯作者：
Arditi, R
影响因子：
8.8
作者：
Hart, D;Shochat, E;Agur, Z
通讯作者：
Agur, Z
影响因子：
15.9
作者：
Kaufman, HL;DeRaffele, G;Marincola, FM
通讯作者：
Marincola, FM
影响因子：
2
作者：
GATENBY, RA
通讯作者：
GATENBY, RA
影响因子：
2
作者：
ARDITI, R;GINZBURG, LR
通讯作者：
GINZBURG, LR