Publications by authors named "Thierry Fredrich"

There are many reasons to try to achieve a good grasp of the distribution of oxygen in the tumor microenvironment. The lack of oxygen - hypoxia - is a main actor in the evolution of tumors and in their growth and appears to be just as important in tumor invasion and metastasis. Mathematical models of the distribution of oxygen in tumors which are based on reaction-diffusion equations provide partial but qualitatively significant descriptions of the measured oxygen concentrations in the tumor microenvironment, especially when they incorporate important elements of the blood vessel network such as the blood vessel size and spatial distribution and the pulsation of local pressure due to blood circulation.

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Blood vessel networks of living organisms continuously adapt their structure under the influence of hemodynamic and metabolic stimuli. For a fixed vessel arrangement, blood flow characteristics still depend crucially on the morphology of each vessel. Vessel diameters adapt dynamically according to internal and external stimuli: Endothelial wall shear stress, intravascular pressure, flow-dependent metabolic stimuli, and electrical stimuli conducted from distal to proximal segments along vascular walls.

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One of many important features of the tumour microenvironment is that it is a place of active Darwinian selection where different tumour clones become adapted to the variety of ecological niches that make up the microenvironment. These evolutionary processes turn the microenvironment into a powerful source of tumour heterogeneity and contribute to the development of drug resistance in cancer. Here, we describe a computational tool to study the ecology of the microenvironment and report results about the ecology of the tumour microenvironment and its evolutionary dynamics.

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During the past years our group published several articles using computer simulations to address the complex interaction of tumors and the vasculature as underlying transport network. Advances in imaging and lab techniques pushed in vitro research of tumor spheroids forward and animal models as well as clinical studies provided more insights to single processes taking part in tumor growth, however, an overall picture is still missing. Computer simulations are a non-invasive option to cumulate current knowledge and form a quasi in vivo system.

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We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression.

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