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体细胞进化的线性过程。

The linear process of somatic evolution.

作者信息

Nowak Martin A, Michor Franziska, Iwasa Yoh

机构信息

Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138, USA.

出版信息

Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14966-9. doi: 10.1073/pnas.2535419100. Epub 2003 Dec 1.

Abstract

Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The "linear process" has the property of cancelling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.

摘要

癌症是一个不良进化过程的结果。细胞会发生改变其表型的突变。尤其危险的是那些增加细胞净繁殖率的突变,从而导致瘤形成,进而发展为癌症。进化动力学的标准模型考虑的是处于对称位置的个体充分混合的群体。在此,我们引入一种空间明确的非对称随机过程,该过程捕捉了多细胞生物组织内进化动力学的基本架构。“线性过程”具有消除细胞间选择差异但保留细胞凋亡保护功能的特性。这种设计可显著减缓体细胞进化速率,从而延迟癌症的发生。

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本文引用的文献

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Somatic selection for and against cancer.支持和对抗癌症的体细胞选择
J Theor Biol. 2003 Dec 7;225(3):377-82. doi: 10.1016/s0022-5193(03)00267-4.
4
The role of chromosomal instability in tumor initiation.染色体不稳定性在肿瘤起始中的作用。
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16226-31. doi: 10.1073/pnas.202617399. Epub 2002 Nov 21.
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Somatic stem cells and the kinetics of mutagenesis and carcinogenesis.体细胞干细胞与诱变和致癌作用的动力学
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10567-70. doi: 10.1073/pnas.162369899. Epub 2002 Jul 29.
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Epidermal stem cells.表皮干细胞
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Two genetic hits (more or less) to cancer.癌症的两次(或多或少)基因打击。
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Stem cells, cancer, and cancer stem cells.干细胞、癌症与癌症干细胞。
Nature. 2001 Nov 1;414(6859):105-11. doi: 10.1038/35102167.
10
Epidermal cell lineage.表皮细胞谱系。
Biochem Cell Biol. 1998;76(6):889-98. doi: 10.1139/bcb-76-6-889.

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