Analysis of a mathematical model for tumor therapy with a fusogenic oncolytic virus

被引:11
|
作者
Jacobsen, Karly [1 ]
Pilyugin, Sergei S. [1 ]
机构
[1] Univ Florida, Dept Math, Gainesville, FL 32611 USA
基金
美国国家科学基金会;
关键词
Oncolytic virus; Tumor; Syncytia; Hyperbolic-parabolic system; Free boundary problem; HERPES-SIMPLEX-VIRUS; REPLICATION-COMPETENT VIRUS; MEMBRANE-GLYCOPROTEINS; GLIOMA VIROTHERAPY; IMMUNE-RESPONSE; MEASLES-VIRUS; CANCER; CELLS; DYNAMICS; GROWTH;
D O I
10.1016/j.mbs.2015.02.009
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Oncolytic virotherapy is a tumor treatment which uses viruses to selectively target and destroy cancer cells. Fusogenic viruses, capable of causing cell-to-cell fusion upon infection of a tumor cell, have shown promise in experimental studies. Fusion causes the formation of large, multinucleated syncytia which eventually leads to cell death. We formulate a partial differential equations model with a moving boundary to describe the treatment of a spherical tumor with a fusogenic oncolytic virus. Fusion, lysis, and budding are incorporated as mechanisms of viral spread, resulting in nonlocal integral terms. A proof is presented for existence and uniqueness of global solutions to the nonlinear hyperbolic-parabolic system. Numerical simulations demonstrate convergence to spatially homogeneous solutions and exponential growth or decay of the tumor radius depending on viral burst size and rate of fusion. Long-term tumor radius is shown to decrease with increasing values of viral burst size while the effect of the rate of fusion on tumor growth is demonstrated to be nonmonotonic. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:169 / 182
页数:14
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