具有非线性免疫反应的耐药性演变模型的动态分析。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Tengfei Wang, Xiufen Zou
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引用次数: 0

摘要

最近的研究利用进化机制来阻止耐药群体的出现。在本文中,我们建立了一个数学模型,该模型综合了激素治疗、免疫疗法以及三种细胞类型(对药物敏感的癌细胞、耐药癌细胞和免疫效应细胞)之间的相互作用。模型进行了动态分析,检验了平衡的存在性和稳定性,从而证实了模型的可解释性。利用现有的前列腺癌数据和文献对模型参数进行了校准。通过对不同免疫效应细胞招募反应下的药物敏感性进行分岔分析,我们发现在弱招募反应下,抗药性癌细胞会迅速生长,在强招募反应下,抗药性癌细胞会维持在较低水平,而在中度招募反应下,抗药性癌细胞和抗药性癌细胞都可能出现。为了量化敏感细胞和抗性细胞的竞争性,我们分别引入了决定竞争结果的综合指标 R1 和 R2。此外,我们还引入了定量指标 CIE1 和 CIE2,分别作为敏感癌细胞和抗性癌细胞免疫效应的综合衡量指标。这两个指标决定了相应的癌细胞能否维持在低水平。我们的研究表明,免疫系统是影响耐药性进化的重要因素,并为如何增强免疫反应以控制耐药性提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamic analysis of a drug resistance evolution model with nonlinear immune response

Recent studies have utilized evolutionary mechanisms to impede the emergence of drug-resistant populations. In this paper, we develop a mathematical model that integrates hormonal treatment, immunotherapy, and the interactions among three cell types: drug-sensitive cancer cells, drug-resistant cancer cells and immune effector cells. Dynamical analysis is performed, examining the existence and stability of equilibria, thereby confirming the model’s interpretability. Model parameters are calibrated using available prostate cancer data and literature. Through bifurcation analysis for drug sensitivity under different immune effector cells recruitment responses, we find that resistant cancer cells grow rapidly under weak recruitment response, maintain at a low level under strong recruitment response, and both may occur under moderate recruitment response. To quantify the competitiveness of sensitive and resistant cells, we introduce the comprehensive measures R1 and R2, respectively, which determine the outcome of competition. Additionally, we introduce the quantitative indicators CIE1 and CIE2 as comprehensive measures of the immune effects on sensitive and resistant cancer cells, respectively. These two indicators determine whether the corresponding cancer cells can maintain at a low level. Our work shows that the immune system is an important factor affecting the evolution of drug resistance and provides insights into how to enhance immune response to control resistance.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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