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• W6064184 abstract "The work presented in this thesis is concerned with modelling the effects of cell movement onthe growth and formation of cell cycle phase specific regions within solid tumours. A model isproposed in the context of multicellular tumour spheroids (MCTS) and includes a simple modelof the cell cycle, where cells move between each cell cycle phase depending on the availabilityof extracellular nutrient, as well as cell movement via chemotaxis, which varies depending uponthe respective cell cycle phase of the cell.Numerical and asymptotic solutions show the model re-produces the well known MCTS structureof an internal quiescent cell region surrounded by a rim of proliferating cells. A further,more interesting result, describes a tumour surrounded by a rim of quiescent cells, with an innerquiescent and an interim proliferating cell region. The resultant solutions are a result of thedifferent cell velocity profiles along with the effects of the cell cycle kinetics in different regions ofthe tumour. The non-linear form of the conservation equations describing the movement of cellsmeans that solutions with spatial discontinuities in the cell concentrations (shocks) are observedfor specific parameter values.Analysis of the effects of the chemotactic response and the cell cycle kinetics, both spatialand temporal, provide insight in to the model's behaviour and shows an understanding of cellcycle kinetics, cell movement and the spatial structure of tumours is important in assistingtherapeutic strategies. The effectiveness of apoptosis, as an anti-cancer strategy, is shown tobe dependent upon the concentration and spatial organisation of proliferating cells within therespective tumour.Comparison with the experimentally verified model of tumour growth developed by Gompertzallows specific model parameters to be expressed in terms of experimentally known variables.Such analysis shows that Gompertz's model is good at predicting the growth of solid tumourswith a proliferating rim, but other models are required to understand the growth of non-uniform,heterogeneous tumours.Experimental justification of the model is provided by considering the observed internalisationof H3 Thymidine labelled cells and inert microspheres within MCTS. Here experimental resultsshow that following adherence to the spheroid edge, the microspheres were all advected towardsthe centre of the spheroids whilst the labelled cells were spread throughout the proliferatingand quiescent outer regions. The cell cycle model which is developed is, unlike previous models,able to account for this observed behaviour. Various simulations are discussed in relation to theoriginal experimental results. These results show the importance of cell movement in providingpossible ways of assisting with drug delivery to the more therapeutically resistant regions ofsolid tumours.Finally the importance of necrosis formation is discussed by a simple extension to the model.Necrosis as a result of quiescent cell death leads to the commonly observed formation of anecrotic core in each case. However, using the model to consider the more recent hypothesisthat apoptosis leads to the formation of necrotic regions provides interesting theoretical results." @default.
• W6064184 created "2016-06-24" @default.
• W6064184 creator A5051202360 @default.
• W6064184 date "2002-03-01" @default.
• W6064184 modified "2023-09-27" @default.
• W6064184 title "Modelling cell movement and the cell cycle in multicellular tumour spheroids." @default.
• W6064184 hasPublicationYear "2002" @default.
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