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建立细胞群体生长模型及其在人类肿瘤细胞系癌症治疗中的应用

Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

作者信息

Basse Britta, Baguley Bruce C, Marshall Elaine S, Wake Graeme C, Wall David J N

机构信息

Biomathematics Research Centre, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.

出版信息

Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):353-68. doi: 10.1016/j.pbiomolbio.2004.01.017.

Abstract

In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines.

摘要

在本文中,我们概述了为模拟细胞群体及癌症治疗效果所开展的工作。我们从一个理论上的单室大小结构细胞群体模型入手,并研究了其渐近稳态大小分布(SSDs)(《关于浮游生物的细胞生长模型》,《MMB JIMA》21(2004年)49)。然而,这些大小分布与通过对人类肿瘤细胞系进行流式细胞术分析实验获得的DNA(大小)分布并不相似(数据来自新西兰奥克兰癌症协会研究中心)。在我们的单室模型中,大小是一个通用术语,但为了获得现实的稳态大小分布,我们选择大小为DNA含量,并设计了一个用于细胞分裂周期的多室数学模型,其中每个室对应细胞周期的一个不同阶段(《数学生物学杂志》47(2003年)295)。然后,我们纳入了另一个室,描述从有丝分裂期可能诱导的细胞凋亡(细胞死亡)(《模拟暴露于抗癌药物紫杉醇的人类肿瘤细胞系中的细胞死亡》,《数学生物学杂志》2004年,即将发表)。这使我们能够将我们的模型与添加了抗癌药物紫杉醇的黑色素瘤细胞系的流式细胞术数据进行比较。该模型给出了紫杉醇对细胞周期影响的动态图景。我们希望使用该模型来描述其他癌症治疗对多种不同细胞系的影响。

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