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肿瘤作为一个器官:肿瘤及其微环境的全面时空建模

The tumor as an organ: comprehensive spatial and temporal modeling of the tumor and its microenvironment.

作者信息

Bloch Naamah, Harel David

机构信息

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 234 Herzl st, 7610001, Rehovot, Israel.

出版信息

BMC Bioinformatics. 2016 Aug 24;17(1):317. doi: 10.1186/s12859-016-1168-5.

Abstract

BACKGROUND

Research related to cancer is vast, and continues in earnest in many directions. Due to the complexity of cancer, a better understanding of tumor growth dynamics can be gleaned from a dynamic computational model. We present a comprehensive, fully executable, spatial and temporal 3D computational model of the development of a cancerous tumor together with its environment.

RESULTS

The model was created using Statecharts, which were then connected to an interactive animation front-end that we developed especially for this work, making it possible to visualize on the fly the on-going events of the system's execution, as well as the effect of various input parameters. We were thus able to gain a better understanding of, e.g., how different amounts or thresholds of oxygen and VEGF (vascular endothelial growth factor) affect the progression of the tumor. We found that the tumor has a critical turning point, where it either dies or recovers. If minimum conditions are met at that time, it eventually develops into a full, active, growing tumor, regardless of the actual amount; otherwise it dies.

CONCLUSIONS

This brings us to the conclusion that the tumor is in fact a very robust system: changing initial values of VEGF and oxygen can increase the time it takes to become fully developed, but will not necessarily completely eliminate it.

摘要

背景

与癌症相关的研究极为广泛,且在多个方向上仍在积极推进。由于癌症的复杂性,通过动态计算模型能够更深入地了解肿瘤生长动力学。我们展示了一个全面的、完全可执行的、关于癌性肿瘤及其周围环境发展的时空三维计算模型。

结果

该模型使用状态图创建,随后连接到我们专门为此工作开发的交互式动画前端,从而能够即时可视化系统执行过程中的实时事件以及各种输入参数的影响。借此,我们能够更好地理解,例如,不同量的氧气和血管内皮生长因子(VEGF)或其阈值如何影响肿瘤的进展。我们发现肿瘤存在一个关键转折点,在此处它要么死亡要么恢复。如果此时满足最低条件,无论实际量如何,它最终都会发展成一个完整的、活跃生长的肿瘤;否则它就会死亡。

结论

这使我们得出结论,肿瘤实际上是一个非常稳健的系统:改变VEGF和氧气的初始值可能会增加其完全发展所需的时间,但不一定能将其完全消除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab79/4995621/abc7fb67929b/12859_2016_1168_Fig1_HTML.jpg

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