用BlenX和Kinfer建模和估计肿瘤收缩动力学

P. Lecca, Ozan Kahramanoğulları, D. Morpurgo, C. Priami, R. Soo
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引用次数: 6

摘要

我们提出CoSBiLab BlenX作为药效学系统建模的开发和分析平台。BlenX与其用于推断动力学参数的辅助工具CoSBiLab KInfer一起,在基于微分方程和基于机制的药效学系统建模方法之间提供了有效的折衷。在本文中,我们用模型来支持这一说法,该模型描述了在接受吉西他滨和卡铂治疗的肺癌患者化疗过程中肿瘤大小的变化。我们的第一个简单的高级模型依赖于一些可识别的和生物学相关的参数。这些参数的估计只需要体内的肿瘤生长曲线,通常在临床环境中可用。这个模型是我们正在进行的工作中必不可少的第一步,我们的目标是用第二个模型解释高级行为。后一种模型结合了药物的分子机制,决定了导致肿瘤缩小的细胞毒性作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modelling and Estimating Dynamics of Tumor Shrinkage with BlenX and Kinfer
We present CoSBiLab BlenX as a development and analysis platform for modeling pharmacodynamical systems. Together with its supporting tool CoSBiLab KInfer for inferring kinetic parameters, BlenX provides an effective compromise between the differential equations-based and mechanisms-based approaches to modeling of pharmacodynamical systems. In this paper, we support this claim with models that describe the tumor size changes over the time course of chemotherapy in lung cancer patients treated with gemcitabine and carboplatin. Our first simple high-level model relies on a few identifiable and biologically relevant parameters. The estimation of these parameters requires only the tumor growth curve in vivo, typically available in the clinical setting. This model is an essential first step of our ongoing work where we aim at explaining the high-level behavior with our second model. This latter model incorporates the molecular machinery of the drug that determines the cytotoxic effect resulting in the shrinkage of the tumor.
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