Cellular and molecular bases of biomineralization in sea urchin embryos

Sea urchin embryos construct their skeleton following a precise gene-regulated time- and space-dependent programme, in concert with factors promoting cell adhesion and differentiation. The biomineral is deposited in a privileged extracellular space produced by the fused filopodia processes of the primary mesenchyme cells, the only cells producing a set of necessary matrix proteins. More than ten years ago we showed for the first time that signals from ectoderm cells promoted the expression of one of the major skeleton matrix genes by the primary mesenchyme cells. Since then, many of the crucial steps of this complex activation cascade, from ectoderm cells to embryonic spicules, have been el…

TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)

ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…

Association Between Tumor Egfr and Kras Mutation Status and Clinical Outcomes in Nsclc Patients Randomized to Sorafenib Plus Best Supportive Care (BSC) or Bsc Alone: Subanalysis of the Phase III Mission Trial

ABSTRACT Background Tumor EGFR and KRas mutations are both predictive and prognostic biomarkers in patients with advanced NSCLC. We analyzed the correlation between these biomarkers and treatment outcomes in a phase III trial of 3rd/4th line sorafenib in patients with NSCLC. Methods The global, randomized, placebo-controlled MISSION trial enrolled 703 patients with advanced relapsed/refractory NSCLC of predominantly non-squamous histology. The primary study endpoint was overall survival (OS). EGFR and KRas mutations were analyzed in archival tumor samples and in circulating tumor DNA isolated from plasma. Results Tumor and/or plasma mutation data were available from 347 patients (49%). EGFR…

Biotecnologie e monitoraggio ambientale: sviluppo e applicazione di biomarcatori molecolari.

Deflazacort in Duchenne dystrophy: Study of long-term effect

A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P < 0.01), in rising from a chair, Gower's maneuver, and walking (P < 0.0025) after 6 months of treatment. After 1 year, all the above changes remained significantly improved and the MRC index was significantly better (P < 0.05) in the treated group. After 2 years, a significant change was found in the MRC index: higher scores in walking, chair rising (P < 0.02), and grade and time of Gower's maneuver (P < 0.05) were found. The mea…

MALATTIA OSSEA DI PAGET NELL’ANZIANO: UNA POSSIBILITÀ DIAGNOSTICA DA NON TRASCURARE

La malattia ossea di Paget è una delle principali alte-razioni del metabolismo scheletrico, seconda per frequenza solo all’osteoporosi. È caratterizzata da un di-sordine focale e progressivo del rimaneggiamento osseo, nel quale il tessuto osseo normale viene rimosso e sostituito con tessuto osseo patologico. La malattia è di solito diagnosticata in soggetti di età superiore ai 55 anni con una maggiore prevalenza nel sesso maschile. Sulla base di reperti autoptici, si è stimato che possa colpire fino al 4% dei soggetti di età superiore ai 50 anni e la probabilità che compaia aumenta con l’età con un’incidenza di circa il 10% nei soggetti molto anziani. I segni clinici vengono solitamente esp…

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, RealWorld Study

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinua…

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes includ…

Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulativ…

αααanti-4.2 Haplotype and heterozygous β° thalassemia in a Sicilian family

The presence of the αααanti-4.2 haplotype and heterozygous β° thalassemia in a Sicilian family is described. These findings confirm the presence in Italy of a leftward deletion (−α4.2) and indicate that this may not be rare. Furthermore, although the β thalassemia determinant in this family has a severe expression, the interaction with the triplicated α gene does not necessarily express itself as thalassemia intermedia.

Genome wide survey of the Toll-like receptor family in the Mediterranean sea urchin

Toll-like receptors (TLRs) represent a conserved family of proteins widely expressed in eukaryotes. They play crucial roles in the innate immune system recognizing different pathogen-associated molecular patterns. In mammals the TLR family comprises 10-13 members, while a huge number of TLR-like genes were recovered in S.purpuratus[1-3]. The Paracentrotus lividus genome project recently generated a new highquality assembly of the genome that represents a valuable resource also for clarifying the evolutionary origin of immune system. In order to identify TLR genes in P.lividus, a genome wide survey was carried out and BLAT searches retrieved 119 TLR genes (PlivTLRs). Ab initio gene predictio…