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单细胞数学模型成功复制胶质母细胞瘤的关键特征:无需“非此即彼”策略。

Single Cell Mathematical Model Successfully Replicates Key Features of GBM: Go-Or-Grow Is Not Necessary.

作者信息

Scribner Elizabeth, Fathallah-Shaykh Hassan M

机构信息

The University of Alabama, Birmingham, Department of Mathematics, Birmingham, Alabama, United States of America.

The University of Alabama, Birmingham, Department of Neurology, Birmingham, Alabama, United States of America.

出版信息

PLoS One. 2017 Jan 3;12(1):e0169434. doi: 10.1371/journal.pone.0169434. eCollection 2017.

Abstract

Glioblastoma (GBM) is a malignant brain tumor that continues to be associated with neurological morbidity and poor survival times. Brain invasion is a fundamental property of malignant glioma cells. The Go-or-Grow (GoG) phenotype proposes that cancer cell motility and proliferation are mutually exclusive. Here, we construct and apply a single glioma cell mathematical model that includes motility and angiogenesis and lacks the GoG phenotype. Simulations replicate key features of GBM including its multilayer structure (i.e.edema, enhancement, and necrosis), its progression patterns associated with bevacizumab treatment, and replicate the survival times of GBM treated or untreated with bevacizumab. These results suggest that the GoG phenotype is not a necessary property for the formation of the multilayer structure, recurrence patterns, and the poor survival times of patients diagnosed with GBM.

摘要

胶质母细胞瘤(GBM)是一种恶性脑肿瘤,一直与神经功能障碍和较差的生存时间相关。脑侵袭是恶性胶质瘤细胞的一个基本特性。“生长或静止”(GoG)表型认为癌细胞的运动性和增殖是相互排斥的。在此,我们构建并应用了一个单一胶质瘤细胞数学模型,该模型包括运动性和血管生成,且缺乏GoG表型。模拟结果再现了GBM的关键特征,包括其多层结构(即水肿、强化和坏死)、与贝伐单抗治疗相关的进展模式,并再现了接受或未接受贝伐单抗治疗的GBM患者的生存时间。这些结果表明,GoG表型对于GBM多层结构的形成、复发模式以及确诊为GBM患者的较差生存时间而言并非必要特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b36/5207515/b3e7aae3b814/pone.0169434.g001.jpg

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