对患者特异性胶质母细胞瘤异种移植物进行解剖感知模拟

Adam A. Malik, Cecilia Krona, Soumi Kundu, Philip Gerlee, Sven Nelander
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引用次数: 0

摘要

患者衍生细胞(PDC)小鼠异种移植在胶质母细胞瘤(GBM)研究中日益成为重要的工具,对于研究特定病例的生长模式和治疗反应至关重要。尽管异种移植模型在这一领域发挥着核心作用,但很少有好的模拟模型可用于探究肿瘤生长动态和支持治疗设计。因此,我们提出了一个新框架,用于在小鼠大脑中模拟特定患者的 GBM。与现有方法不同的是,我们的模拟利用了高分辨率的小鼠脑解剖图,得出了与实验观察结果非常一致的患者特异性结果。为了便于将我们的模型与组织学数据拟合,我们使用了近似贝叶斯计算方法。由于我们的模型使用的参数很少,反映的是生长、侵袭和生态位的依赖性,因此非常适合病例比较和治疗效果探查。我们展示了如何通过扰动不同的模型参数来模拟不同的治疗方法。我们希望小鼠异种移植肿瘤的硅学复制可以改善治疗效果评估,提高临床前 GBM 研究的统计能力。
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Anatomically aware simulation of patient-specific glioblastoma xenografts
Patient-derived cells (PDC) mouse xenografts are increasingly important tools in glioblastoma (GBM) research, essential to investigate case-specific growth patterns and treatment responses. Despite the central role of xenograft models in the field, few good simulation models are available to probe the dynamics of tumor growth and to support therapy design. We therefore propose a new framework for the patient-specific simulation of GBM in the mouse brain. Unlike existing methods, our simulations leverage a high-resolution map of the mouse brain anatomy to yield patient-specific results that are in good agreement with experimental observations. To facilitate the fitting of our model to histological data, we use Approximate Bayesian Computation. Because our model uses few parameters, reflecting growth, invasion and niche dependencies, it is well suited for case comparisons and for probing treatment effects. We demonstrate how our model can be used to simulate different treatment by perturbing the different model parameters. We expect in silico replicates of mouse xenograft tumors can improve the assessment of therapeutic outcomes and boost the statistical power of preclinical GBM studies.
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