Identification of common and distinctive mechanisms of resistance to different anti-IGF-IR agents in Ewing's sarcoma

IGF system contributes significantly to many human malignancies. Targeting IGF-I receptor (IGF-IR) has been reported to be active against several tumors, but particular efficacy was observed only against a minority of Ewing's sarcoma patients. Identification of mechanisms of acquired resistance to anti- IGF-IR agents is mandatory to individualize their use in clinics and optimize cure costs. In this study, we compared gene expression profiles of cells made resistant with three different anti-IGF-IR drugs (human antibodies AVE1642, Figitumumab, or tyrosine kinase inhibitor NVP-AEW541) to highlight common and distinctive mechanisms of resistance. Among common mechanisms, we identified two molecular signatures that distinguish sensitive from resistant cells. Annotation analysis indicated some common altered pathways, such as insulin signaling, MAPK pathway, endocytosis, and modulation of some members of the interferon-induced transmembrane protein family. Among distinctive pathways/ processes, resistance to human antibodies involves mainly genes regulating neural differentiation and angiogenesis, whereas resistance to NVP-AEW541 is mainly associated with alterations in genes concerning inflammation and antigen presentation. Evaluation of the common altered pathways indicated that resistant cells seem to maintain intact the IGF-IR internalization/degradation route of sensitive cells but constantly down-regulated its expression. In resistant cells, the loss of proliferative stimulus, normally sustained by IGF-I/IGF-IR autocrine loop in Ewing's sarcoma cells, is compensated by transcriptional up-regulation of IGF-II and insulin receptor-A; this signaling seems to favor the MAPK pathway over the v-akt murine thymoma viral oncogene homolog 1 pathway. Overall, complexity of IGF system requires analytical evaluation of its components to select those patients that may really benefit from this targeted therapy and support the idea of cotargeting IGF-IR and insulin receptor-A to increase the efficacy

Giorgio Vasari a Palazzo Abatellis. Percorsi del Rinascimento in Sicilia

La mostra si inserisce nell'ambito delle celebrazioni per i 500 anni della nascita di Giorgio Vasari (1511-2011), ricorrenza che, nel corso dell'anno, \ue8 stata oggetto di numerosi eventi culturali italiani e internazionali. L'iniziativa nasce dalla collaborazione tra la Biblioteca Centrale della Regione siciliana "A. Bombace", la sezione "Sfera" del Dipartimento di Architettura dell'Universit\ue0 degli Studi di Palermo, e la Galleria Interdisciplinare Regionale della Sicilia, istituzione che custodisce, nella prestigiosa sede di Palazzo Abatellis, due grandi dipinti su tavola di Vasari, costituenti le ricurve parti laterali del trittico della "Caduta della manna" realizzato nel 1545 per il refettorio di Santa Maria di Monteoliveto a Napoli. Le lunette vasariane, esposte in modo permanente dal 2009 ma ancora quasi del tutto sconosciute a studiosi e pubblico, per l'occasione sono state ricollocate secondo gli originali rapporti dimensionali con il perduto quadro centrale e poste in relazione con il disegno preparatorio dello stesso Vasari, oggi custodito presso l'Ecole nationale superieure des beaux-arts di Parigi. Il percorso analitico, che si \ue8 avvalso anche del prezioso contributo di Claudia Conforti, tra le pi\uf9 autorevoli studiose dell'artista aretino, e delle competenze tecniche dell'Associazione culturale LapiS, \ue8 stato svolto secondo tre tematiche connesse alla poliedrica attivit\ue0 vasariana e al suo contesto culturale: la pittura e l'arte del disegno, la produzione letteraria, l'architettura. Al patrimonio pittorico e grafico della Galleria, riconducibile a quella che lo stesso Vasari definisce \uabmaniera moderna\ubb, sono stati quindi associati preziosi volumi a stampa, a partire dalla rara edizione del 1568 delle "Vite de' pi\uf9 eccellenti architetti, pittori e scultori italiani", e pannelli illustrativi riferiti a opere siciliane di architetti e scultori citati nelle "Vite" vasariane, costituenti alcune pregnanti testimonianze del Rinascimento in Sicili

The Seascape of Demersal Fish Nursery Areas in the North Mediterranean Sea, a First Step Towards the Implementation of Spatial Planning for Trawl Fisheries

The identification of nursery grounds and other essential fish habitats of exploited stocks is a key requirement for the development of spatial conservation planning aimed at reducing the adverse impact of fishing on the exploited populations and ecosystems. The reduction in juvenile mortality is particularly relevant in the Mediterranean and is considered as one of the main prerequisites for the future sustainability of trawl fisheries. The distribution of nursery areas of 11 important commercial species of demersal fish and shellfish was analysed in the European Union Mediterranean waters using time series of bottom trawl survey data with the aim of identifying the most persistent recruitment areas. A high interspecific spatial overlap between nursery areas was mainly found along the shelf break of many different sectors of the Northern Mediterranean indicating a high potential for the implementation of conservation measures. Overlap of the nursery grounds with existing spatial fisheries management measures and trawl fisheries restricted areas was also investigated. Spatial analyses revealed considerable variation depending on species and associated habitat/depth preferences with increased protection seen in coastal nurseries and minimal protection seen for deeper nurseries (e.g. Parapenaeus longirostris 6%). This is partly attributed to existing environmental policy instruments (e.g. Habitats Directive and Mediterranean Regulation EC 1967/2006) aiming at minimising impacts on coastal priority habitats such as seagrass, coralligenous and maerl beds. The new knowledge on the distribution and persistence of demersal nurseries provided in this study can support the application of spatial conservation measures, such as the designation of no-take Marine Protected Areas in EU Mediterranean waters and their inclusion in a conservation network. The establishment of no-take zones will be consistent with the objectives of the Common Fisheries Policy applying the ecosystem approach to fisheries management and with the requirements of the Marine Strategy Framework Directive to maintain or achieve seafloor integrity and good environmental status.Versión del editor4,411

Nitric oxide synthase-dependent "on/Off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: Skeletal muscle versus cardiac muscle

10.1016/j.niox.2013.03.005Nitric Oxide - Biology and Chemistry321-12NIOX

Differential NOS expression in freshwater and aestivating Protopterus dolloi (lungfish): Heart vs kidney readjustments

10.1016/j.niox.2007.10.004Nitric Oxide - Biology and Chemistry1811-10NIOX

Spatial distribution pattern of European hake Merluccius merluccius (Pisces: Merlucciidae) in the Mediterranean Sea

The present study provides updated information on the occurrence, abundance and biomass distribution patterns and length frequencies of Merluccius merluccius in the Mediterranean Sea, by analysing a time series of data from the Medi- terranean International Trawl Surveys (MEDITS) from 1994 to 2015. The highest values of abundance and biomass were observed in the Sardinian Seas. The use of a generalized additive model, in which standardized biomass indices (kg km–2) were analysed as a function of environmental variables, explained how ecological factors could affect the spatio-temporal distribution of European hake biomass in the basin. High biomass levels predicted by the model were observed especially at 200 m depth and between 14°C and 18°C, highlighting the preference of the species for colder waters. A strong reduction of biomass was observed since the year 2009, probably due to the strengthening of the seasonal thermocline that had greatly reduced the availability of food. The general decrease in biomass of several stocks of anchovy and sardine, preys of European hake, might be indirectly connected to the decreasing biomass detected in the present study. The length analysis shows me- dian values lower than 200 mm total length of most of the investigated areas

Insulin-like growth factor-1 (IGF-1): Demographic, clinical and laboratory data in 120 consecutive adult patients with thalassaemia major

Introduction: IGF-1 deficiency in TM patients in children and adolescents has been attributed to chronic anemia and hypoxia, chronic liver disease, iron overload and other associated endocrinopathies, e.g. growth hormone deficiency (GHD). Few data are available in the literature regarding adult TM patients and growth disorders. The aim of this study was to measure IGF-1 values and other clinical data in a large number of adult patients with TM to evaluate the possible relationships between them. Patients and Methods: A cohort of 120 adult patients with TM was studied for plasma levels of IGF-1. Plasma total IGF-1 was determined by chemiluminescent immunometric assay (CLIA) method. In eleven patients (3 females) the GH response during glucagon stimulation test (GST) was also evaluated. Results: Fifty percent of patients (33 males and 27 females) had IGF-1 levels <- 2 SDs below normative values for healthy subjects matched for age and sex. In these patients endocrine complications and elevations of aminotransferases (ALT) were more common compared to TM patients with IGF1 > -2SDs. In multivariate regression analyses, height, weight, BMI, serum ferritin, ALT, HCV serology and left ventricular ejection fraction (LVEF) were not significantly related to IGF-1, but a significant correlation was found in females between HCV-RNA positivity and IGF-1, ALT and serum ferritin. AGHD was diagnosed in 6 (4 males) out of 11 patients (54.5%) who had glucagon stimulation tests and in 5 out of 8 (62.5%) with IGF-1 <-2SD. The mean age of patients with GHD was 39.3 years (range: 25-49 years, median: 39 years) versus 35.8 years (range: 27-45 years, median: 37.5 years) in non-GHD patients. A positive correlation between GH peak after GST and IGF-1 level was found (r: 0.6409; p: < 0.05). Conclusions: In 50% of TM patients the IGF-1 levels were 2SDs below average values for healthy individuals. IGF-1 deficiency was more common in TM patients with associated endocrine complications, and a significant correlation was found in HCV-RNA positive females among IGF-1, ALT, and serum ferritin. Further data in a larger group of patients are needed to confirm whether IGF-1 level <-2 SDs may be a potential criterion for additional studies in TM patients. This datum could avoid performing GH stimulation tests in the majority of them