Transforming growth factor beta (TGF(beta) induces epithelial-mesenchymal transition (EMT), which correlates with sternness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by... Show moreTransforming growth factor beta (TGF(beta) induces epithelial-mesenchymal transition (EMT), which correlates with sternness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by TGF beta withdrawal and correlates with metastatic colonization. Whether TGF beta promotes sternness and invasiveness simultaneously via EMT remains unclear. We established a breast cancer cell model expressing red fluorescent protein (RFP) under the E-cadherin promoter. In 2D cultures, TGF beta induced EMT, generating RFPlow cells with a mesenchymal transcriptome, and regained RFP, with an epithelial transcriptome, after MET induced by TGF beta withdrawal. RFPlow cells generated robust mammospheres, with epithelio-mesenchymal cell surface features. Mammospheres that were forced to adhere generated migratory cells, devoid of RFP, a phenotype which was inhibited by a TGF beta receptor kinase inhibitor. Further stimulation of RFPlow mammospheres with TGF beta suppressed the generation of motile cells, but enhanced mammosphere growth. Accordingly, mammary fat-pad-transplanted mammospheres, in the absence of exogenous TGF beta treatment, established lung metastases with evident MET (RFPhigh cells). In contrast, TGF beta-treated mammospheres revealed high tumour-initiating capacity, but limited metastatic potential. Thus, the biological context of partial EMT and MET allows TGF beta to differentiate between pro-sternness and pro-invasive phenotypes. Show less
Heer, F. de; Kluin, J.; Elkhoury, G.; Jondeau, G.; Enriquez-Sarano, M.; Schafers, H.J.; ... ; Aortic Valve Repair Res Network In 2019
Objectives: Current national registries are lacking detailed pathology-driven analysis and long-term patients outcomes. The Heart Valve Society (HVS) aortic valve (AV) repair research network... Show moreObjectives: Current national registries are lacking detailed pathology-driven analysis and long-term patients outcomes. The Heart Valve Society (HVS) aortic valve (AV) repair research network started the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR) to evaluate long-term patient outcomes of AV repair and replacement. The purpose of the current report is to describe the AVIATOR initiative and report in a descriptive manner the patients included.Methods: The AV repair research network includes surgeons, cardiologists, and scientists and established an online database compliant with the guidelines for reporting valve-related events. Prospective inclusion started from January 2013. Adult patients (18 years or older) who were operated on between 1995 and 2017 with complete procedural specification of the type of repair/replacement were selected for descriptive analysis.Results: Currently 58 centers from 17 countries include 4896 patients with 89% AV repair (n = 4379) versus 11% AV replacement (n = 517). AV repair was either isolated (28%), or associated with tubular/partial root replacement (22%) or valve-sparing root replacement (49%) with an in-hospital mortality of 0.5%, 1.7%, and 1.2%, respectively. AV replacement was either isolated (24%), associated with tubular/partial root replacement (17%) or root replacement (59%) with an in-hospital mortality of 1%, 2.6%, and 2.0%, respectively.Conclusions: The multicenter surgical AVIATOR registry, by applying uniform definitions, should provide a solid evidence base to evaluate the place of repair versus replacement on the basis of long-term patient outcomes. Obtaining data completeness and adequate representation of all surgery types remain challenging. Toward the near future AVIATOR-medical will start to study natural history, as will AVIATOR-kids, with a focus on pediatric disease. Show less
