Stochastic modeling suggests that noise reduces differentiation efficiency by inducing a heterogeneous drug response in glioma differentiation therapy
文献类型：期刊论文
| 作者 | Sun,Xiaoqiang1,2; Zhang,Jiajun2; Zhao,Qi3,4; Chen,Xing5; Zhu,Wenbo1; Yan,Guangmei1; Zhou,Tianshou2 |
| 刊名 | BMC Systems Biology
 |
| 出版日期 | 2016-08-11 |
| 卷号 | 10期号:1 |
| 关键词 | Stochastic modeling Ultrasensitivity Noise Differentiation efficiency Drug resistance Glioma differentiation therapy |
| ISSN号 | 1752-0509 |
| DOI | 10.1186/s12918-016-0316-x |
| 英文摘要 | AbstractBackgroundGlioma differentiation therapy is a novel strategy that has been used to induce glioma cells to differentiate into glia-like cells. Although some advances in experimental methods for exploring the molecular mechanisms involved in differentiation therapy have been made, a model-based comprehensive analysis is still needed to understand these differentiation mechanisms and improve the effects of anti-cancer therapeutics. This type of analysis becomes necessary in stochastic cases for two main reasons: stochastic noise inherently exists in signal transduction and phenotypic regulation during targeted therapy and chemotherapy, and the relationship between this noise and drug efficacy in differentiation therapy is largely unknown.ResultsIn this study, we developed both an additive noise model and a Chemical-Langenvin-Equation model for the signaling pathways involved in glioma differentiation therapy to investigate the functional role of noise in the drug response. Our model analysis revealed an ultrasensitive mechanism of cyclin D1 degradation that controls the glioma differentiation induced by the cAMP inducer cholera toxin (CT). The role of cyclin D1 degradation in human glioblastoma cell differentiation was then experimentally verified. Our stochastic simulation demonstrated that noise not only renders some glioma cells insensitive to cyclin D1 degradation during drug treatment but also induce heterogeneous differentiation responses among individual glioma cells by modulating the ultrasensitive response of cyclin D1. As such, the noise can reduce the differentiation efficiency in drug-treated glioma cells, which was verified by the decreased evolution of differentiation potential, which quantified the impact of noise on the dynamics of the drug-treated glioma cell population.ConclusionOur results demonstrated that targeting the noise-induced dynamics of cyclin D1 during glioma differentiation therapy can increase anti-glioma effects, implying that noise is a considerable factor in assessing and optimizing anti-cancer drug interventions. |
| 语种 | 英语 |
| WOS记录号 | BMC:10.1186/S12918-016-0316-X |
| 出版者 | BioMed Central |
| 源URL | [http://ir.amss.ac.cn/handle/2S8OKBNM/347]  |
| 专题 | 中国科学院数学与系统科学研究院 |
| 通讯作者 | Sun,Xiaoqiang; Zhu,Wenbo; Zhou,Tianshou |
| 作者单位 | 1.Sun Yat-Sen University; Zhong-shan School of Medicine 2.Sun Yat-Sen University; School of Mathematical and Computational Science 3.Liaoning University; School of Mathematics 4.Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province 5.China University of Mining and Technology; School of Information and Electrical Engineering |
| 推荐引用方式 GB/T 7714 | Sun,Xiaoqiang,Zhang,Jiajun,Zhao,Qi,et al. Stochastic modeling suggests that noise reduces differentiation efficiency by inducing a heterogeneous drug response in glioma differentiation therapy[J]. BMC Systems Biology,2016,10(1). |
| APA | Sun,Xiaoqiang.,Zhang,Jiajun.,Zhao,Qi.,Chen,Xing.,Zhu,Wenbo.,...&Zhou,Tianshou.(2016).Stochastic modeling suggests that noise reduces differentiation efficiency by inducing a heterogeneous drug response in glioma differentiation therapy.BMC Systems Biology,10(1). |
| MLA | Sun,Xiaoqiang,et al."Stochastic modeling suggests that noise reduces differentiation efficiency by inducing a heterogeneous drug response in glioma differentiation therapy".BMC Systems Biology 10.1(2016). |
入库方式： OAI收割
来源：数学与系统科学研究院
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