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癌症发展和生长的计算建模:多尺度建模和多尺度建模。

Computational Modelling of Cancer Development and Growth: Modelling at Multiple Scales and Multiscale Modelling.

机构信息

ICM, University of Warsaw, ul. Pawińskiego 5a, 02-106, Warsaw, Poland.

Division of Mathematics, University of Dundee, Dundee, DD1 4HN, Scotland, UK.

出版信息

Bull Math Biol. 2018 May;80(5):1366-1403. doi: 10.1007/s11538-017-0292-3. Epub 2017 Jun 20.

Abstract

In this paper, we present two mathematical models related to different aspects and scales of cancer growth. The first model is a stochastic spatiotemporal model of both a synthetic gene regulatory network (the example of a three-gene repressilator is given) and an actual gene regulatory network, the NF-[Formula: see text]B pathway. The second model is a force-based individual-based model of the development of a solid avascular tumour with specific application to tumour cords, i.e. a mass of cancer cells growing around a central blood vessel. In each case, we compare our computational simulation results with experimental data. In the final discussion section, we outline how to take the work forward through the development of a multiscale model focussed at the cell level. This would incorporate key intracellular signalling pathways associated with cancer within each cell (e.g. p53-Mdm2, NF-[Formula: see text]B) and through the use of high-performance computing be capable of simulating up to [Formula: see text] cells, i.e. the tissue scale. In this way, mathematical models at multiple scales would be combined to formulate a multiscale computational model.

摘要

在本文中,我们提出了两个与癌症生长的不同方面和规模相关的数学模型。第一个模型是一个合成基因调控网络(以三基因阻遏子为例)和实际基因调控网络 NF-[Formula: see text]B 通路的随机时空模型。第二个模型是一个基于力的个体模型,用于研究无血管实体肿瘤的发展,特别是针对肿瘤索,即围绕中央血管生长的一团癌细胞。在每种情况下,我们将我们的计算模拟结果与实验数据进行比较。在最后的讨论部分,我们概述了如何通过开发以细胞为重点的多尺度模型来推进这项工作。这将包括每个细胞内与癌症相关的关键细胞内信号通路(例如 p53-Mdm2、NF-[Formula: see text]B),并通过使用高性能计算能够模拟多达[Formula: see text]个细胞,即组织规模。通过这种方式,将在多个尺度上的数学模型进行组合,以构建一个多尺度计算模型。

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