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重组麻疹病毒用于癌症病毒疗法的建模

Modeling of cancer virotherapy with recombinant measles viruses.

作者信息

Bajzer Zeljko, Carr Thomas, Josić Kresimir, Russell Stephen J, Dingli David

机构信息

Biomathematics Resource and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Guggenheim 1611b, Rochester, MN 55905, USA.

出版信息

J Theor Biol. 2008 May 7;252(1):109-22. doi: 10.1016/j.jtbi.2008.01.016. Epub 2008 Feb 1.

Abstract

The Edmonston vaccine strain of measles virus has potent and selective activity against a wide range of tumors. Tumor cells infected by this virus or genetically modified strains express viral proteins that allow them to fuse with neighboring cells to form syncytia that ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. We present a model of tumor and virus interactions based on established biology and with proper accounting of the free virus population. The range of model parameters is estimated by fitting to available experimental data. The stability of equilibrium states corresponding to complete tumor eradication, therapy failure and partial tumor reduction is discussed. We use numerical simulations to explore conditions for which the model predicts successful therapy and tumor eradication. The model exhibits damped, as well as stable oscillations in a range of parameter values. These oscillatory states are organized by a Hopf bifurcation.

摘要

麻疹病毒的埃德蒙斯顿疫苗株对多种肿瘤具有强大且选择性的活性。被这种病毒或基因改造株感染的肿瘤细胞会表达病毒蛋白,使它们能够与相邻细胞融合形成最终死亡的多核巨细胞。此外,受感染的细胞可能会产生新的病毒颗粒,进而感染更多的肿瘤细胞。我们基于已确立的生物学原理并适当考虑游离病毒群体,提出了一个肿瘤与病毒相互作用的模型。通过拟合现有实验数据来估计模型参数的范围。讨论了对应于肿瘤完全根除、治疗失败和肿瘤部分缩小的平衡状态的稳定性。我们使用数值模拟来探索模型预测成功治疗和肿瘤根除的条件。该模型在一系列参数值范围内表现出阻尼振荡以及稳定振荡。这些振荡状态由霍普夫分岔组织。

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