How tumour-induced vascular changes alter angiogenesis: Insights from a computational model.

A computational model was developed to describe experimentally observed vascular changes induced by the introduction of a tumour on a mouse equipped with a dorsal skinfold chamber. The vascular structure of the host tissue was segmented from in vivo images and transposed into the computational framework. Simulations of tumour-induced vascular changes were performed and include the destabilizing effects of the growth factor VEGF on the integrity of the vessels walls. The integration of those effects, that include alteration of the vessel wall elasticity and wall breaching, were required to realistically reproduce the experimental observations. The model was then used to investigate the importance of the vascular changes for oxygen delivery and tumour development. To that end, we compared simulations obtained with a dynamic vasculature with those obtained with a static one. The results showed that the tumour growth was strongly impeded by the constant vascular changes. More precisely, it is the angiogenic process itself that was affected by vascular changes occurring in bigger upstream vessels and resulting in a less efficient angiogenic network for oxygen delivery. As a consequence, tumour cells are mostly kept in a non-proliferative hypoxic state. Tumour dormancy thus appears as one potential consequence of the intense vascular changes in the host tissue.

[Effects of fine particulate matter from on bronchial epithelial cells]. / Effets des particules fines sur les cellules épithéliales bronchiques.

INTRODUCTION: Ambient air contains a variety of pollutants including solid particles. Human bronchial epithelial cells (HBEC) play a key role following inhalation of these toxic particles. In a cell culture system of HBEC, we investigated the effects of several fractions of Lyons air-derived particles on cell viability/proliferation and production of the inflammatory mediators IL-8 and TGF-ß. METHODS: Air particles were collected in Lyon (France) by filtration of the air and impaction on filters located on a tapered element oscillating microbalance. Several diameter-based fractions of particles were prepared. HBEC were then exposed to different concentrations of these fractions. RESULTS: HBEC survival was not altered after 48hours of culture in the presence of particles regardless of their diameter and concentration. A dose-dependent inhibitory effect on cell growth was observed for all fractions. The particles caused an increase of both TGF-ß and Il-8 protein levels as a function of their diameters and/or concentrations. CONCLUSION: Air-derived particle fractions exhibit both an inhibitory effect on cell proliferation and a pro-inflammatory activity on HBEC.