Tanaka M L, Debinski W, Puri I K
Department of Orthopaedic Surgery, Wake Forest University, Winston-Salem, North Carolina, USA.
Cell Prolif. 2009 Oct;42(5):637-46. doi: 10.1111/j.1365-2184.2009.00631.x. Epub 2009 Jul 17.
Gliomas are an important form of brain cancer, with high mortality rate. Mathematical models are often used to understand and predict their behaviour. However, using current modeling techniques one must choose between simulating individual cell behaviour and modeling tumours of clinically significant size.
We propose a hybrid compartment-continuum-discrete model to simulate glioma growth and malignant cell invasion. The discrete portion of the model is capable of capturing intercellular interactions, including cell migration, intercellular communication, spatial cell population heterogeneity, phenotype differentiation, epigenetic events, proliferation, and apoptosis. Combining this with a compartment and continuum model allows clinically significant tumour sizes to be evaluated.
This model is used to perform multiple simulations to determine sensitivity to changes in important model parameters, specifically, the fundamental length parameter, necrotic cell degradation rate, rate of cell migration, and rate of phenotype transformation. Using these values, the model is able to simulate tumour growth and invasion behaviour, observed clinically. This mathematical model provides a means to simulate various tumour development scenarios, which may lead to a better understanding of how altering fundamental parameters can influence neoplastic progression.
神经胶质瘤是脑癌的一种重要形式,死亡率很高。数学模型常被用于理解和预测其行为。然而,使用当前的建模技术,必须在模拟单个细胞行为和对具有临床意义大小的肿瘤进行建模之间做出选择。
我们提出了一种混合的隔室 - 连续体 - 离散模型来模拟神经胶质瘤的生长和恶性细胞侵袭。该模型的离散部分能够捕捉细胞间相互作用,包括细胞迁移、细胞间通讯、空间细胞群体异质性、表型分化、表观遗传事件、增殖和凋亡。将其与隔室和连续体模型相结合,可以评估具有临床意义的肿瘤大小。
该模型用于进行多次模拟,以确定对重要模型参数变化的敏感性,具体而言,即基本长度参数、坏死细胞降解率、细胞迁移率和表型转化率。利用这些值,该模型能够模拟临床上观察到的肿瘤生长和侵袭行为。这个数学模型提供了一种模拟各种肿瘤发展情况的方法,这可能有助于更好地理解改变基本参数如何影响肿瘤进展。