3,230 research outputs found
Multiscale modelling of tumour growth and therapy: the influence of vessel normalisation on chemotherapy
Following the poor clinical results of antiangiogenic drugs, particularly when applied in isolation, tumour biologists and clinicians are now turning to combinations of therapies in order to obtain better results. One of these involves vessel normalisation strategies. In this paper, we investigate the effects on tumour growth of combinations of antiangiogenic and standard cytotoxic drugs, taking into account vessel normalisation. An existing multiscale framework is extended to include new elements such as tumour-induced vessel dematuration. Detailed simulations of our multiscale framework allow us to suggest one possible mechanism for the observed vessel normalisation-induced improvement in the efficacy of cytotoxic drugs: vessel dematuration produces extensive regions occupied by quiescent (oxygen-starved) cells which the cytotoxic drug fails to kill. Vessel normalisation reduces the size of these regions, thereby allowing the chemotherapeutic agent to act on a greater number of cells
The impact of cell crowding and active cell movement on vascular tumour growth
A multiscale model for vascular tumour growth is presented which includes systems of ordinary differential equations for the cell cycle and regulation of apoptosis in individual cells, coupled to partial differential equations for the spatio-temporal dynamics of nutrient and key signalling chemicals. Furthermore, these subcellular and tissue layers are incorporated into a cellular automaton framework for cancerous and normal tissue with an embedded vascular network. The model is the extension of previous work and includes novel features such as cell movement and contact inhibition. We presented a detailed simulation study of the effects of these additions on the invasive behaviour of tumour cells and the tumour's response to chemotherapy. In particular, we find that cell movement alone increases the rate of tumour growth and expansion, but that increasing the tumour cell carrying capacity leads to the formation of less invasive dense hypoxic tumours containing fewer tumour cells. However, when an increased carrying capacity is combined with significant tumour cell movement, the tumour grows and spreads more rapidly, accompanied by large spatio-temporal fluctuations in hypoxia, and hence in the number of quiescent cells. Since, in the model, hypoxic/quiescent cells produce VEGF which stimulates vascular adaptation, such fluctuations can dramatically affect drug delivery and the degree of success of chemotherapy
Modelling the response of vascular tumours to chemotherapy: A multiscale approach
An existing multiscale model is extended to study the response of a vascularised tumour to treatment with chemotherapeutic drugs which target proliferating cells. The underlying hybrid cellular automaton model couples tissue-level processes (e.g. blood flow, vascular adaptation, oxygen and drug transport) with cellular and subcellular phenomena (e.g. competition for space, progress through the cell cycle, natural cell death and drug-induced cell kill and the expression of angiogenic factors). New simulations suggest that, in the absence of therapy, vascular adaptation induced by angiogenic factors can stimulate spatio-temporal oscillations in the tumour's composition.\ud
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Numerical simulations are presented and show that, depending on the choice of model parameters, when a drug which kills proliferating cells is continuously infused through the vasculature, three cases may arise: the tumour is eliminated by the drug; the tumour continues to expand into the normal tissue; or, the tumour undergoes spatio-temporal oscillations, with regions of high vascular and tumour cell density alternating with regions of low vascular and tumour cell density. The implications of these results and possible directions for future research are also discussed
Cost of porcine reproductive and respiratory syndrome virus at individual farm level – An economic disease model
Porcine reproductive and respiratory syndrome (PRRS) is reported to be among the diseases with the highest economic impact in modern pig production worldwide. Yet, the economic impact of the disease at farm level is not well understood as, especially in endemically infected pig herds, losses are often not obvious. It is therefore difficult for farmers and veterinarians to appraise whether control measures such as virus elimination or vaccination will be economically beneficial for their farm. Thus, aim of this study was to develop an epidemiological and economic model to determine the costs of PRRS for an individual pig farm. In a production model that simulates farm outputs, depending on farm type, farrowing rhythm or length of suckling period, an epidemiological model was integrated. In this, the impact of PRRS infection on health and productivity was estimated. Financial losses were calculated in a gross margin analysis and a partial budget analysis based on the changes in health and production parameters assumed for different PRRS disease severities. Data on the effects of endemic infection on reproductive performance, morbidity and mortality, daily weight gain, feed efficiency and treatment costs were obtained from literature and expert opinion. Nine different disease scenarios were calculated, in which a farrow-to-finish farm (1000 sows) was slightly, moderately or severely affected by PRRS, based on changes in health and production parameters, and either in breeding, in nursery and fattening or in all three stages together. Annual losses ranged from a median of € 75′724 (90% confidence interval (C.I.): € 78′885–€ 122′946), if the farm was slightly affected in nursery and fattening, to a median of € 650′090 (90% C.I. € 603′585–€ 698′379), if the farm was severely affected in all stages. Overall losses were slightly higher if breeding was affected than if nursery and fattening were affected. In a herd moderately affected in all stages, median losses in breeding were € 46′021 and € 422′387 in fattening, whereas costs were € 25′435 lower in nursery, compared with a PRRSV-negative farm. The model is a valuable decision-support tool for farmers and veterinarians if a farm is proven to be affected by PRRS (confirmed by laboratory diagnosis). The output can help to understand the need for interventions in case of significant impact on the profitability of their enterprise. The model can support veterinarians in their communication to farmers in cases where costly disease control measures are justified
Exploring Agricultural Production Systems and Their Fundamental Components with System Dynamics Modelling
Agricultural production in the United States is undergoing marked changes due to rapid shifts in consumer demands, input costs, and concerns for food safety and environmental impact. Agricultural production systems are comprised of multidimensional components and drivers that interact in complex ways to influence production sustainability. In a mixed-methods approach, we combine qualitative and quantitative data to develop and simulate a system dynamics model that explores the systemic interaction of these drivers on the economic, environmental and social sustainability of agricultural production. We then use this model to evaluate the role of each driver in determining the differences in sustainability between three distinct production systems: crops only, livestock only, and an integrated crops and livestock system. The result from these modelling efforts found that the greatest potential for sustainability existed with the crops only production system. While this study presents a stand-alone contribution to sector knowledge and practice, it encourages future research in this sector that employs similar systems-based methods to enable more sustainable practices and policies within agricultural production
Structural adaptation in normal and cancerous vasculature
The dynamics of cancerous tissue growth involves the complex interaction of a number of phenomena interacting over a range of temporal and spatial scales. While several processes involved have been studied, the adaptation of the vasculature within a growing tumour has thus far received little attention. We consider a hybrid cellular automaton model which analyses the interaction between the tumour vascular network and tissue growth. We compute the temporal behaviour of the cancerous cell population under different hypotheses of structural adaptation in the vasculature. This may provide a possible method of determining experimentally which adaptation mechanisms are at work
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