缺氧对肿瘤生长动力学影响的细胞自动机模型

M. Al-Mamun, W. Srisukkham, C. Fall, R. Bass, Md. Alamgir Hossain, D. Farid
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引用次数: 3

摘要

癌症是西方世界最大的杀手之一;在英国,每两分钟就有人被诊断出患有癌症。肿瘤的生长和发展是一个复杂的生物学过程,通常从单个细胞的基因突变开始。它开始于早期或无血管期,生长受到营养扩散的限制,然后是血管期,血管生成发生,通过肿瘤血管生成因子的分泌刺激血管生成,最后是转移期,肿瘤从起源部位扩散到身体周围的远处部位。在细胞水平上考虑这些事件时,这些过程涉及许多微环境参数,如氧浓度、低血糖、酸度、缺氧(缺氧)、细胞-细胞粘附、细胞迁移和细胞-细胞外基质相互作用。本文提出了一个考虑缺氧作为肿瘤生长微环境约束的计算模型。该模型建立在二维细胞自动机网格上,采用人工神经网络建立肿瘤细胞信号网络。在这个模型中,每个肿瘤细胞都可以做出自己的决定。通过改变不同的氧浓度,在模型中实现了缺氧影响。结果表明,由于缺氧,肿瘤团块中引入了缺氧。该模型测量了肿瘤侵袭和凋亡细胞的数量,以支持缺氧对无血管肿瘤生长有重要影响。该模型可以从计算的角度更好地了解缺氧对肿瘤生长的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A cellular automaton model for hypoxia effects on tumour growth dynamics
Cancer is one of the biggest killers in the western world; every two minutes someone is diagnosed with cancer in the UK. Tumour growth and progression is a complex biological process, normally beginning with genetic mutations in a single cell. It starts with the early or avascular phase where growth is limited by nutrient diffusion, then the vascular stage where angiogenesis occurs to stimulate blood vessel production by the secretion of tumour angiogenesis factors and finally the metastasitic phase where the tumour spreads from the site of origin to distant sites around the body. While considering these events at the cellular level, these processes involve many microenvironment parameters like oxygen concentration, hypoglycaemia, acidity, hypoxia (lack of oxygen), cell-cell adhesion, cell migration and cell-extracellular matrix interactions. In this paper, a computational model is proposed which considered hypoxia as a microenvironment constraint of tumour growth. The model is built on two dimensional cellular automata grid and artificial neural network is considered for establishing signaling network of tumour cells. Each tumour cell can take its own decision in this model. A hypoxia impact was implemented in the model by varying different oxygen concentrations. The results show that hypoxia was introduced in the tumour mass due to lack of oxygen. The model measured tumour invasion and the number of apoptotic cells to support that hypoxia has a critical impacts on avascular tumour growth. This model could inform a better understanding of the impacts of hypoxia in tumour growth from the computational point of view.
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