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Hybrid mathematical model of glioma progression
Authors:M L Tanaka†§  W Debinski‡  I K Puri†§
Institution:Department of Orthopaedic Surgery, Wake Forest University, Winston-Salem, North Carolina, USA;, Virginia Tech–Wake Forest University School of Biomedical Engineering, Blacksburg, VA, USA;, Brain Tumor Center of Excellence, Department of Neurosurgery, Radiation Oncology, and Cancer Biology, Wake Forest University, Winston-Salem, North Carolina, USA;, and Department of Engineering Science and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
Abstract:Objectives:  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.
Materials and Methods:  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.
Results and Conclusions:  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.
Keywords:
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