Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts

A New Agile Hybridization Approach and a Set of Related Guidelines for Mechatronic Product Development

Part 11: Model Based Systems EngineeringInternational audienceIn industry 4.0, the growing incorporation of cyber-physical systems (CPS) into manufacturing facilities composed of mechatronic products brings forth the need of reducing development cost while maintaining the quality and in parallel the need to adapt changes along the lifecycle of the product development. Most of the traditional development methods fail to solve such new challenges. However, some agile methods, widely used in the software industry, could meet these requirements. It is then essential to identify the criticalities of agile methods regarding mechatronic system development specificities.As a result, our research work focuses on combining traditional and agile approaches to improve mechatronic products development in a changing market context. The development of hybrid approach is based on the analysis of traditional, agile methods and consideration of challenges in the development of mechatronic products. To illustrate the advantages of such hybridization, we propose a first hybrid approach consisting of some elements of the Scrum method (the most popular agile approach) into the V-Model. Differentiating advantages of this new approach, compared to other agile methods, include the freedom to propagate necessary changes in product architecture during the development of its different modules.This new approach focuses on the hybridization of traditional and agile methods and the required guidelines to adopt and use for enhanced mechatronic products development. These guidelines are the base for changing the organizational culture and values which were previously associated with traditional development approaches