Refine
Language
- English (18)
Has Fulltext
- yes (18)
Keywords
- haptotaxis (4)
- multiscale model (4)
- asymptotic behavior (2)
- cancer cell invasion (2)
- degenerate diffusion (2)
- delay (2)
- global existence (2)
- pH-taxis (2)
- parabolic system (2)
- weak solution (2)
Faculty / Organisational entity
We propose and study a strongly coupled PDE-ODE system with tissue-dependent degenerate diffusion and haptotaxis that can serve as a model prototype for cancer cell invasion through the
extracellular matrix. We prove the global existence of weak solutions and illustrate the model behaviour by numerical simulations for a two-dimensional setting.
We propose and study a strongly coupled PDE-ODE-ODE system modeling cancer cell invasion through a tissue network
under the go-or-grow hypothesis asserting that cancer cells can either move or proliferate. Hence our setting features
two interacting cell populations with their mutual transitions and involves tissue-dependent degenerate diffusion and
haptotaxis for the moving subpopulation. The proliferating cells and the tissue evolution are characterized by way of ODEs
for the respective densities. We prove the global existence of weak solutions and illustrate the model behaviour by
numerical simulations in a two-dimensional setting.
We propose a model for acid-mediated tumor invasion involving two different scales: the microscopic one, for the dynamics of intracellular protons and their exchange with their extracellular counterparts, and the macroscopic scale of interactions between tumor cell and normal cell populations, along with the evolution of extracellular protons. We also account for the tactic behavior of cancer cells, the latter being assumed to biase their motion according to a gradient of extracellular protons (following [2,31] we call this pH taxis). A time dependent (and also time delayed) carrying capacity for the tumor cells in response to the effects of acidity is considered as well. The global well posedness of the resulting multiscale model is proved with a regularization and fixed point argument. Numerical simulations are performed in order to illustrate the behavior of the model.
We prove the global existence, along with some basic boundedness properties, of weak solutions to a PDE-ODE system modeling the multiscale invasion of tumor cells through the surrounding tissue matrix. The model has been proposed in [22] and accounts on the macroscopic level for the evolution of cell and tissue densities, along with the concentration of a chemoattractant, while on the subcellular level it involves the binding of integrins to soluble and insoluble components of the peritumoral region. The connection between the two scales is realized with the aid of a contractivity function characterizing the ability of the tumor cells to adapt their motility behavior
to their subcellular dynamics.
The resulting system, consisting of three partial and three ordinary differential equations including a temporal delay, in particular involves chemotactic and haptotactic cross-diffusion. In order to overcome technical obstacles stemming from the corresponding highest-order interaction terms, we base our analysis on a certain functional, inter alia involving the cell and tissue densities in the diffusion and haptotaxis terms respectively, which is shown to enjoy a quasi-dissipative property. This will be used as a starting point for the derivation of a series of integral estimates finally allowing for the construction of a generalized solution as the limit of solutions to suitably regularized problems.
We investigate a PDE-ODE system describing cancer cell invasion in a tissue network. The model is an extension of the multiscale setting in [28,40], by considering two subpopulations of tumor cells interacting mutually and with the surrounding tissue. According to the go-or-grow hypothesis, these subpopulations consist of moving and proliferating cells, respectively. The mathematical setting also accommodates the effects of some therapy approaches. We prove the global existence of weak solutions to this model and perform numerical simulations to illustrate its behavior for different therapy strategies.
Cancer cell migration is an essential feature in the process of tumor spread and establishing of metastasis. It characterizes the invasion observed on the level of the cell population, but it is also tightly connected to the events taking place on the subcellular level. These are conditioning the motile and proliferative behavior of the cells, but are also influenced by it. In this work we propose a multiscale model linking these two levels and aiming to assess their interdependence. On the subcellular, microscopic scale it accounts for integrin binding to soluble and insoluble components present in the peritumoral environment, which is seen as the onset of biochemical events leading to changes in the cell's ability to contract and modify its shape. On the macroscale of the cell population this leads to modifications in the diffusion and haptotaxis performed by the tumor cells and implicitly to changes in the tumor environment. We prove the (local) well posedness of our model and perform numerical simulations in order to illustrate the model predictions.
Starting from the two-scale model for pH-taxis of cancer cells introduced in [1], we consider here an extension accounting for tumor heterogeneity w.r.t. treatment sensitivity and a treatment approach including chemo- and radiotherapy. The effect of peritumoral region alkalinization on such therapeutic combination is investigated with the aid of numerical simulations.
The aim is to prove global existence and uniqueness of square integrable solutions to a class of multiscale models for tumour
cell migration involving chemotaxis, haptotaxis, and subcellular dynamics. This approach allows the tissue
fibre and cell densities as well as concentrations of chemotactic signals to be less regular and the conditions sufficient for well-posedness of the multiscale model to be less restrictive than in previous settings.
We propose a model for glioma patterns in a microlocal tumor environment under
the influence of acidity, angiogenesis, and tissue anisotropy. The bottom-up model deduction
eventually leads to a system of reaction–diffusion–taxis equations for glioma and endothelial cell
population densities, of which the former infers flux limitation both in the self-diffusion and taxis
terms. The model extends a recently introduced (Kumar, Li and Surulescu, 2020) description of
glioma pseudopalisade formation with the aim of studying the effect of hypoxia-induced tumor
vascularization on the establishment and maintenance of these histological patterns which are typical
for high-grade brain cancer. Numerical simulations of the population level dynamics are performed
to investigate several model scenarios containing this and further effects.
Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns (not necessarily of Turing type), including pseudopalisades, can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related .
SDE-driven modeling of phenotypically heterogeneous tumors: The influence of cancer cell stemness
(2018)
We deduce cell population models describing the evolution of a tumor (possibly interacting with its
environment of healthy cells) with the aid of differential equations. Thereby, different subpopulations
of cancer cells allow accounting for the tumor heterogeneity. In our settings these include cancer
stem cells known to be less sensitive to treatment and differentiated cancer cells having a higher
sensitivity towards chemo- and radiotherapy. Our approach relies on stochastic differential equations
in order to account for randomness in the system, arising e.g., by the therapy-induced decreasing
number of clonogens, which renders a pure deterministic model arguable. The equations are deduced
relying on transition probabilities characterizing innovations of the two cancer cell subpopulations,
and similarly extended to also account for the evolution of normal tissue. Several therapy approaches
are introduced and compared by way of tumor control probability (TCP) and uncomplicated tumor
control probability (UTCP). A PDE approach allows to assess the evolution of tumor and normal
tissue with respect to time and to cell population densities which can vary continuously in a given set
of states. Analytical approximations of solutions to the obtained PDE system are provided as well.
A nonlocal stochastic model for intra- and extracellular proton dynamics in a tumor is proposed.
The intracellular dynamics is governed by an SDE coupled to a reaction-diffusion
equation for the extracellular proton concentration on the macroscale. In a more general context
the existence and uniqueness of solutions for local and nonlocal
SDE-PDE systems are established allowing, in particular, to analyze the proton dynamics model both,
in its local version and the case with nonlocal path dependence.
Numerical simulations are performed
to illustrate the behavior of solutions, providing some insights into the effects of randomness on tumor acidity.
We consider the multiscale model for glioma growth introduced in a previous work and extend it to account
for therapy effects. Thereby, three treatment strategies involving surgical resection, radio-, and
chemotherapy are compared for their efficiency. The chemotherapy relies on inhibiting the binding
of cell surface receptors to the surrounding tissue, which impairs both migration and proliferation.
Cancer research is not only a fast growing field involving many branches of science, but also an intricate and diversified field rife with anomalies. One such anomaly is the
consistent reliance of cancer cells on glucose metabolism for energy production even in a normoxic environment. Glycolysis is an inefficient pathway for energy production and normally is used during hypoxic conditions. Since cancer cells have a high demand for energy
(e.g. for proliferation) it is somehow paradoxical for them to rely on such a mechanism. An emerging conjecture aiming to explain this behavior is that cancer cells
preserve this aerobic glycolytic phenotype for its use in invasion and metastasis. We follow this hypothesis and propose a new model
for cancer invasion, depending on the dynamics of extra- and intracellular protons, by building upon the existing ones. We incorporate random perturbations in the intracellular proton dynamics to account
for uncertainties affecting the cellular machinery. Finally, we address the well-posedness of our setting and use numerical simulations to illustrate the model predictions.
We propose a multiscale model for tumor cell migration in a tissue network. The system of equations involves a structured population model for the tumor cell density, which besides time and
position depends on a further variable characterizing the cellular state with respect to the amount
of receptors bound to soluble and insoluble ligands. Moreover, this equation features pH-taxis and
adhesion, along with an integral term describing proliferation conditioned by receptor binding. The
interaction of tumor cells with their surroundings calls for two more equations for the evolution of
tissue fibers and acidity (expressed via concentration of extracellular protons), respectively. The
resulting ODE-PDE system is highly nonlinear. We prove the global existence of a solution and
perform numerical simulations to illustrate its behavior, paying particular attention to the influence
of the supplementary structure and of the adhesion.
Glioma is a common type of primary brain tumor, with a strongly invasive potential, often exhibiting nonuniform, highly irregular growth. This makes it difficult to assess
the degree of extent of the tumor, hence bringing about a supplementary challenge for the treatment. It is therefore necessary to understand the
migratory behavior of glioma in greater detail.
In this paper we propose a multiscale model for glioma growth and migration. Our model couples the microscale dynamics (reduced to the binding of surface receptors to the
surrounding tissue) with a kinetic transport equation for the cell density on the mesoscopic level of individual cells. On the latter scale we also include the
proliferation of tumor cells via effects of interaction with the tissue. An adequate parabolic scaling yields a convection-diffusion-reaction equation, for which the coefficients
can be explicitly determined from the information about the tissue obtained by diffusion tensor imaging. Numerical simulations relying on DTI measurements confirm the biological
findings that glioma spreads
along white matter tracts.
We propose and analyze a multiscale model for acid-mediated tumor invasion
accounting for stochastic effects on the subcellular level.
The setting involves a PDE of reaction-diffusion-taxis type describing the evolution of the tumor cell density,
the movement being directed towards pH gradients in the local microenvironment,
which is coupled to a PDE-SDE system characterizing the
dynamics of extracellular and intracellular proton concentrations, respectively.
The global well-posedness of the model is shown and
numerical simulations are performed in order to illustrate the solution behavior.
In this paper we propose a phenomenological model for the formation of an interstitial gap between the tumor and the stroma. The gap
is mainly filled with acid produced by the progressing edge of the tumor front. Our setting extends existing models for acid-induced tumor invasion models to incorporate
several features of local invasion like formation of gaps, spikes, buds, islands, and cavities. These behaviors are obtained mainly due to the random dynamics at the intracellular
level, the go-or-grow-or-recede dynamics on the population scale, together with the nonlinear coupling between the microscopic (intracellular) and macroscopic (population)
levels. The wellposedness of the model is proved using the semigroup technique and 1D and 2D numerical simulations are performed to illustrate model predictions and draw
conclusions based on the observed behavior.