The urokinase plasminogen activating system in thyroid cancer: clinical implications

The urokinase plasminogen activator (uPA) system (uPAS) comprises the uPA, its cell membrane receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the plasminogen in the serine protease plasmin, involved in a number of physiopathological processes requiring basement membrane (BM) or extracellular matrix (ECM) remodelling, including tumor progression and metastasis. The tumor-promoting role of PAS is not limited to the degradation of ECM and BM required for local diffusion and spread to distant sites of malignant cells, but widens to tumor cell proliferation, adhesion and migration, intravasation, growth at the metastatic site and neoangiogenesis. The relevance of uPAS in cancer progression has been confirmed by several studies which documented an increased expression of uPA, uPAR and PAI-1 in different human malignancies, and a positive correlation between the levels of one or more of them and a poor prognosis. For these reasons, the uPAS components have aroused considerable interest as suitable targets for anticancer therapy, and several pharmacological approaches aimed at inhibiting the uPA and/or uPAR expression or function in preclinical and clinical settings have been described. In the present manuscript, we will first glance at uPAS biological functions in human cancer progression and its clinical significance in terms of prognosis and therapy. We will then review the main findings regarding expression and function of uPAS components in thyroid cancer tissues along with the experimental and clinical evidence suggesting its potential value as molecular prognostic marker and therapeutic target in thyroid cancer patients.

Cities at risk: status of Italian planning system in reducing seismic and hydrological risks

Italy and its urban systems are under high seismic and hydrogeological risks. The awareness about the role of human activities in the genesis of disasters is achieved in the scientific debate, as well as the role of urban and regional planning in reducing risks. The paper reviews the state of Italian major cities referred to hydrogeological and seismic risk by: 1) extrapolating data and maps about seismic hazard and landslide risk concerning cities with more than 50.000 inhabitants and metropolitan contexts, and 2) outlining how risk reduction is framed in Italian planning system (at national and regional levels). The analyses of available data and the review of the normative framework highlight the existing gaps in addressing risk reduction: nevertheless a wide knowledge about natural risks afflicting Italian territory and an articulated regulatory framework, the available data about risks are not exhaustive, and risk reduction policies and multidisciplinary pro-active approaches are only partially fostered and applied.