Wallace Dorothy I, Dunham Ann, Chen Paula X, Chen Michelle, Huynh Milan, Rheingold Evan, Prosper Olivia
Department of Mathematics, HB 6188, Dartmouth College, Hanover, NH 03768, USA.
Department of Mathematics, University of Kentucky, Lexington, KY 40506, USA.
Comput Math Methods Med. 2016;2016:3628124. doi: 10.1155/2016/3628124. Epub 2016 Dec 1.
Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, as spheroids or . This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy- and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-. The monolayer model is extended to a five-dimensional nonlinear model of tumor spheroid growth and treatment that includes compartments of the cell cycle (, , /) as well as quiescent () and necrotic () cells. Monolayer treatment data for 15-deoxy- is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.
研究人员观察到，肿瘤细胞对治疗的反应因细胞是单层生长、呈球体生长还是其他生长方式而异。本研究使用了文献中关于用15 - 脱氧处理SK - N - SH神经母细胞瘤细胞单层的数据，并将其与未处理的作为多细胞球体生长的SK - N - SH神经母细胞瘤细胞的生长速率数据相结合。针对未处理和处理后的单层数据集构建了一个线性模型，该模型根据对照和用15 - 脱氧处理的单层情况的生长、死亡和细胞周期数据进行了调整。将单层模型扩展为肿瘤球体生长和治疗的五维非线性模型，该模型包括细胞周期的各个阶段（、、/）以及静止（）和坏死（）细胞。使用15 - 脱氧的单层治疗数据来推导在类似治疗下球体反应的预测。在短时间治疗中，球体反应不如单层反应明显。模拟结果表明，实验室研究中观察到的单层培养与球体培养对治疗反应的差异是肿瘤球体生理学的自然结果，而不是对治疗有任何特殊抗性。
