包括突变和遗传不稳定性在内的肿瘤发生动力学建模。

IF 0.8 4区 数学 Q4 BIOLOGY
Artur C Fassoni, Hyun M Yang
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引用次数: 2

摘要

肿瘤发生被描述为一个多步骤的过程,其中每一步都与基因改变有关,其方向是逐渐将正常细胞及其后代转化为恶性肿瘤。在这项工作中,我们提出了一个癌症发生和发展的数学模型,考虑了三种人群:正常细胞、癌前细胞和癌细胞。该模型考虑了肿瘤的三个特征:对生长信号的自给自足、对抗生长信号的不敏感和逃避细胞凋亡。通过使用非线性表达来描述从癌前细胞到癌细胞的突变,该模型将遗传不稳定性作为肿瘤进展的使能特征。并进行了详细的数学分析。结果表明,细胞凋亡和组织修复系统是肿瘤发展的第一道屏障。这些机制中必须有一个被破坏了,癌症才能从单个突变细胞发展而来。结果还表明,侵袭性癌细胞的存在为不太适应的癌前细胞的存活开辟了道路。以乳腺癌实验数据为基础,采用参数值进行数值模拟,并根据一些参数估计了单个突变细胞达到可检测大小所需的时间。我们发现细胞凋亡和突变的速率对肿瘤进展的速度和临床检测所需的时间有很大的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modeling dynamics for oncogenesis encompassing mutations and genetic instability.

Tumorigenesis has been described as a multistep process, where each step is associated with a genetic alteration, in the direction to progressively transform a normal cell and its descendants into a malignant tumour. Into this work, we propose a mathematical model for cancer onset and development, considering three populations: normal, premalignant and cancer cells. The model takes into account three hallmarks of cancer: self-sufficiency on growth signals, insensibility to anti-growth signals and evading apoptosis. By using a nonlinear expression to describe the mutation from premalignant to cancer cells, the model includes genetic instability as an enabling characteristic of tumour progression. Mathematical analysis was performed in detail. Results indicate that apoptosis and tissue repair system are the first barriers against tumour progression. One of these mechanisms must be corrupted for cancer to develop from a single mutant cell. The results also show that the presence of aggressive cancer cells opens way to survival of less adapted premalignant cells. Numerical simulations were performed with parameter values based on experimental data of breast cancer, and the necessary time taken for cancer to reach a detectable size from a single mutant cell was estimated with respect to some parameters. We find that the rates of apoptosis and mutations have a large influence on the pace of tumour progression and on the time it takes to become clinically detectable.

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来源期刊
CiteScore
2.20
自引率
0.00%
发文量
15
审稿时长
>12 weeks
期刊介绍: Formerly the IMA Journal of Mathematics Applied in Medicine and Biology. Mathematical Medicine and Biology publishes original articles with a significant mathematical content addressing topics in medicine and biology. Papers exploiting modern developments in applied mathematics are particularly welcome. The biomedical relevance of mathematical models should be demonstrated clearly and validation by comparison against experiment is strongly encouraged. The journal welcomes contributions relevant to any area of the life sciences including: -biomechanics- biophysics- cell biology- developmental biology- ecology and the environment- epidemiology- immunology- infectious diseases- neuroscience- pharmacology- physiology- population biology
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