Using a novel modeling approach based on the so-called environmental stress level (ESL), we develop a mathematical model to describe systematically the collective influence of oxygen concentration and stiffness of the extracellular matrix on the response of tumor cells to a combined chemotherapeutic treatment. We perform Bayesian calibrations of the resulting model using particle filters, with in vitro experimental data for different hepatocellular carcinoma cell lines. The calibration results support the validity of our mathematical model. Furthermore, they shed light on individual as well as synergistic effects of hypoxia and tissue stiffness on tumor cell dynamics under chemotherapy.

翻译：基于所谓的环境应激水平（ESL）这一新型建模方法，我们构建了一个数学模型，系统描述氧气浓度与细胞外基质刚度对肿瘤细胞联合化疗反应的协同影响。我们采用粒子滤波方法对所得模型进行贝叶斯校准，并利用不同肝细胞癌细胞系的体外实验数据进行验证。校准结果支持了我们数学模型的合理性，同时揭示了缺氧与组织刚度在化疗条件下对肿瘤细胞动力学的单独及协同作用机制。