Nikolaos Sfakianakis

Nikolaos Sfakianakis, Niklas Kolbe, Nadja Hellmann et al.

We propose a multiscale model of the invasion of the extracellular matrix by two types of cancer cells, the differentiated cancer cells and the cancer stem cells. We assume that the epithelial mesenchymal-like transition between them is driven primarily by the epidermal growth factors. We moreover take into account the transidifferentiation program of the cancer stem cells and the cancer associated fibroblast cells as well as the fibroblast-driven remodelling of the extracellular matrix. The proposed haptotaxis model combines the macroscopic phenomenon of the invasion of the extracellular matrix with the microscopic dynamics of the epidermal growth factors. We analyse our model in a component-wise manner and compare our findings with the literature. We investigate pathological situations regarding the epidermal growth factors and accordingly propose "mathematical-treatment" scenarios to control the aggressiveness of the tumour.

Niklas Kolbe, Jana Katuchova, Nikolaos Sfakianakis et al.

In the present work we investigate the chemotactically and proteolytically driven tissue invasion by cancer cells. The model employed is a system of advection-reaction-diffusion equations that features the role of the serine protease urokinase-type plasminogen activator. The analytical and numerical study of this system constitutes a challenge due to the merging, emerging, and travelling concentrations that the solutions exhibit. Classical numerical methods applied to this system necessitate very fine discretization grids to resolve these dynamics in an accurate way. To reduce the computational cost without sacrificing the accuracy of the solution, we apply adaptive mesh refinement techniques, in particular h-refinement. Extended numerical experiments exhibit that this approach provides with a higher order, stable, and robust numerical method for this system. We elaborate on several mesh refinement criteria and compare the results with the ones in the literature. We prove, for a simpler version of this model, $L^\infty$ bounds for the solutions, we study the stability of its conditional steady states, and conclude that it can serve as a test case for further development of mesh refinement techniques for cancer invasion simulations.

Niklas Kolbe, Maria Lukacova-Medvidova, Nikolaos Sfakianakis et al.

We present a problem-suited numerical method for a particularly challenging cancer invasion model. This model is a multiscale haptotaxis advection-reaction-diffusion system that describes the macroscopic dynamics of two types of cancer cells coupled with microscopic dynamics of the cells adhesion on the extracellular matrix. The difficulties to overcome arises from the non-constant advection and diffusion coefficients, a time delay term, as well as stiff reaction terms. Our numerical method is a second order finite volume implicit-explicit scheme adjusted to include a) non-constant diffusion coefficients in the implicit part, b) an interpolation technique for the time delay, and c) a restriction on the time increment for the stiff reaction terms.

Maria Lukacova-Medvidova, Nikolaos Sfakianakis

Non-uniform grids and mesh adaptation have been a growing part of numerical simulation over the past years. It has been experimentally noted that mesh adaptation leads not only to locally improved solution but also to numerical stability of the underlying method. There have been though only few results on the mathematical analysis of these schemes due to the lack of proper tools that incorporate both the time evolution and the mesh adaptation step of the overall algorithm. In this paper we provide a method to perform the analysis of the mesh adaptation method, including both the mesh reconstruction and evolution of the solution. We moreover employ this method to extract sufficient conditions -on the adaptation of the mesh- that stabilize a numerical scheme in the sense of the entropy dissipation.

Nadja Hellmann, Niklas Kolbe, Nikolaos Sfakianakis

Current biological knowledge supports the existence of a secondary group of cancer cells within the body of the tumour that exhibits stem cell-like properties. These cells are termed Cancer Stem Cells (CSCs}, and as opposed to the more usual Differentiated Cancer Cells (DCCs), they exhibit higher motility, they are more resilient to therapy, and are able to metastasize to secondary locations within the organism and produce new tumours. The origin of the CSCs is not completely clear; they seem to stem from the DCCs via a transition process related to the Epithelial-Mesenchymal Transition (EMT) that can also be found in normal tissue. In the current work we model and numerically study the transition between these two types of cancer cells, and the resulting "ensemble" invasion of the extracellular matrix. This leads to the derivation and numerical simulation of two systems: an algebraic-elliptic system for the transition and an advection-reaction-diffusion system of Keller-Segel taxis type for the invasion.

Nikolaos Sfakianakis

We consider 3-point numerical schemes for scalar Conservation Laws, that are oscillatory either to their dispersive or anti-diffusive nature. Oscillations are responsible for the increase of the Total Variation (TV); a bound on which is crucial for the stability of the numerical scheme. It has been noticed (\cite{Arvanitis.2001}, \cite{Arvanitis.2004}, \cite{Sfakianakis.2008}) that the use of non-uniform adaptively redefined meshes, that take into account the geometry of the numerical solution itself, is capable of taming oscillations; hence improving the stability properties of the numerical schemes. In this work we provide a model for studying the evolution of the extremes over non-uniform adaptively redefined meshes. Based on this model we prove that proper mesh reconstruction is able to control the oscillations; we provide bounds for the Total Variation (TV) of the numerical solution. We moreover prove under more strict assumptions that the increase of the TV -due to the oscillatory behaviour of the numerical schemes- decreases with time; hence proving that the overall scheme is TV Increase-Decreasing (TVI-D).