Melanoma contains CD133 and ABCG2 positive cells with enhanced tumorigenic potential

The failure to eradicate most cancers and in particular melanoma may be as fundamental as a misidentification of the target. The identification of cancer stem/initiating cells within the tumour population with a crucial role for tumour formation may open new pharmacological perspectives. Our data show three main novelties for human melanoma: firstly, melanoma biopsy contains a subset of cells expressing CD133 (CD133+) and the latter is able to develop a Mart-1 positive tumour in NOD-SCID mice. Secondly, the WM115, a human melanoma cell line, has been found to express both CD133 and ABCG2 markers. This cell line grows as floating spheroids, expresses typical progenitors and mature neuronal/oligodendrocyte markers and is able to transdifferentiate into astrocytes or mesenchymal lineages under specific growth conditions. As in xenografts generated with CD133+ biopsy melanoma cells, those produced by the cell line displayed lower levels of CD133 and ABCG2. Thirdly, the WM115 cells express the most important angiogenic and lymphoangiogenic factors such as notch 4, prox1 and podoplanin which can cooperate in the development of the tumourigenic capability of melanoma in vivo. Therefore, in this study, we demonstrate the presence of stem/initiating subsets in melanoma both in biopsy and in an established melanoma cell line grown in vitro and in xenografts. Interestingly, considering that melanoma gives metastasis primarily through lymphatic vessels, herein, we demonstrated that a melanoma cell line expresses typical lymphoangiogenic factors

Reperfusion Injury after ischemic Stroke Study (RISKS): single-centre (Florence, Italy), prospective observational protocol study

Introduction Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood\u2013brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury. Methods and analysis Observational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered at http://www. clinicaltrials. gov ( ClinicalTrials. gov ID: NCT03041753). Ethics and dissemination The study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Universit\ue0 degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis. Trial registration number NCT03041753

Terapia farmacologica dell'influenza e delle sue complicanze

L'influenza \ue8 una patologia respiratoria causata da virus influenzali di tipo A (pi\uf9 comuni) e di tipo B. La prevenzione mediante i vaccini \ue8 la procedura pi\uf9 pratica e pi\uf9 conveniente per il controllo dei virus influenzali. Attualmente \ue8 possibile attuare sia prevenzione che trattamento dell'influenza mediante farmaci antivirali, in alcune popolazioni particolari ed in soggetti ad alto rischio. I farmaci antivirali possono contrastare l'azione dei virus e per essere efficaci debbono essere assunti entro 36 ore dall'esposizione ai virus. I farmaci attualmente disponibili appartengono a due categorie: i bloccanti M2 e gli inibitori della neuraminidasi. I primi sono caratterizzati da elevata biodisponibilit\ue0 orale e relativa tollerabilit\ue0 ma sono attivi solo nei confronti di virus di tipo A. Inoltre presentano una relativamente rapido sviluppo di resistenza. I secondi sono ben tollerati e sono attivi nei confronti di virus di tipo A e B e possiedono un potenziale di resistenza inferiore a quello dei bloccanti M2. Le superinfezioni batteriche nel corso di patologie respiratorie virali rappresentano un fenomeno clinicamente ben documentato. Le epidemie di influenza sono accompagnate da un aumento di ricoveri per polmonite batterica sostenuta da pneumococco, H. influenzae e S. aureus e da un incremento di incidenza di infezioni da meningococco. Le complicanze batteriche dell'influenza necessitano terapia antibiotica ma non giustificano l'uso sistematico di antibiotici in corso di patologie esclusivamente virali

Cancer stem cells and therapeutic perspectives

The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for increasing evolution toward malignancy. Herein, we discuss the evidences reported in literature on existence of cancer stem cells in several tumors and mechanisms of the extrinsic and intrinsic circuitry controlling stem cell fate as well as their possible connections to cancer. In particular, the review will focus on recent results on conserved Polycomb Group (PcG) gene family, an epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. There are two distinct multiprotein PcG complexes identified, Polycomb repressive complex (PRC) 1 and 2. The fact that either PRC1 Bmil than PRC2 SU(Z)12 components are implicated in self-renewal stem cells and up-regulated in several kind of human cancer, confirm the importance of (dc)regulation of the PcG genes in cancer and stem cell biology. Moreover, Bmil and SU(Z)12 are downstream target of Sonic hedgehog (Shh) and Writ signaling respectively, providing for a connection between epigenetic change regulators (PcG) and developmental-signaling pathways. Finally, potential therapies using inhibitors acting on cancer stem cell population such as cyclopamine, an inhibitor of hedgehog signalling, 6-bromoindirubin-3'-oxime (BIO) which acts on GSK3 and inhibitors of beta-catenin signaling such as exisulind and the tyrosine-kinase inhibitor ST1571/Gleevac/imatinib will also discuss

A 3D gravity model of crustal structure in the Central-Eastern Alpine sector

Assuming as a starting model the pattern of the Moho boundary as interpreted in a recent study on the basis of the available DSS profiles, a preliminary 3D gravity model of the crustal structures in the Central-Eastern Alpine sector is proposed. The aim of the present work is to confirm the seismic results concerning the Moho and to better shape the main discontinuities in the intermediate and upper crust, where the seismic data are too scattered to allow a reliable interpretation. The gravity field is calculated along twelve cross-sections oriented S-N and crossing the Alpine range from the Padan-Venetian plain to the Bavarian molasse and to the Austrian calcareous Alps. The westernmost section coincides with the European Geotraverse while the easternmost one is positioned at the longitude of about 14ºeast. The assumed density model is very simple (only 6 layers); for each unit the density is maintained constant. The model describes a European mantle dipping southwards underneath an overlapping, uplifted Adriatic mantle. As far as the lower crust is concerned, its top is found at depths between 18 and 28 km, the deepest values being reached in the south-eastern sector; the density appears higher in the Adriatic domain than in the European one and the Adriatic lower crust seems to be deeply indented northwards. The low density surface layers appear very thin in a large area of the northwestern sector, while in the south and southeast their thickness reaches about 10 km. This study must be considered as a complement to the seismic interpretation both as a validation of the model of the deep crust and Moho boundary and as an additional source of information on the upper crust

A 3D gravity model of crustal structure in the Central-Eastern Alpine sector

Assuming as a starting model the pattern of the Moho boundary as interpreted in a recent study on the basis of the available DSS profiles, a preliminary 3D gravity model of the crustal structures in the Central-Eastern Alpine sector is proposed. The aim of the present work is to confirm the seismic results concerning the Moho and to better shape the main discontinuities in the intermediate and upper crust, where the seismic data are too scattered to allow a reliable interpretation. The gravity field is calculated along twelve cross-sections oriented S-N and crossing the Alpine range from the Padan-Venetian plain to the Bavarian molasse and to the Austrian calcareous Alps. The westernmost section coincides with the European Geotraverse while the easternmost one is positioned at the longitude of about 14ºeast. The assumed density model is very simple (only 6 layers); for each unit the density is maintained constant. The model describes a European mantle dipping southwards underneath an overlapping, uplifted Adriatic mantle. As far as the lower crust is concerned, its top is found at depths between 18 and 28 km, the deepest values being reached in the south-eastern sector; the density appears higher in the Adriatic domain than in the European one and the Adriatic lower crust seems to be deeply indented northwards. The low density surface layers appear very thin in a large area of the northwestern sector, while in the south and southeast their thickness reaches about 10 km. This study must be considered as a complement to the seismic interpretation both as a validation of the model of the deep crust and Moho boundary and as an additional source of information on the upper crust