University of Catania

About: University of Catania is a education organization based out in Catania, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 14599 authors who have published 41195 publications receiving 1032705 citations. The organization is also known as: Università degli Studi di Catania & Universita degli Studi di Catania.

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

Abstract: // James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Giuseppe Montalto 2 , Melchiorre Cervello 3 , Massimo Libra 4 , Saverio Candido 4 , Grazia Malaponte 4 , Maria C. Mazzarino 4 , Paolo Fagone 4 , Ferdinando Nicoletti 4 , Jorg Basecke 5 , Sanja Mijatovic 6 , Danijela Maksimovic-Ivanic 6 , Michele Milella 7 , Agostino Tafuri 8 , Francesca Chiarini 9 , Camilla Evangelisti 9 , Lucio Cocco 10 , Alberto M. Martelli 9,10 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA 2 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 3 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy 4 Department of Bio-Medical Sciences, University of Catania, Catania, Italy 5 Department of Medicine, University of Gottingen, Gottingen, Germany 6 Department of Immunology, Instititue for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia 7 Regina Elena National Cancer Institute, Rome, Italy 8 Sapienza, University of Rome, Department of Cellular Biotechnology and Hematology, Rome, Italy 9 Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute, Bologna, Italy 10 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy Correspondence: James A. McCubrey, email: // Keywords : Targeted Therapy, Therapy Resistance, Cancer Stem Cells, Raf, Akt, PI3K, mTOR Received : September 12, 2012, Accepted : October 18, 2012, Published : October 20, 2012 Abstract The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS ) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.

Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study

Abstract: Summary Background The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS. Methods 137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus. Findings MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7·4 [SD 4·2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11·2 [4·5] years; p Interpretation Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.

Increased Sclerostin Serum Levels Associated with Bone Formation and Resorption Markers in Patients with Immobilization-Induced Bone Loss

Abstract: Context: Sclerostin, a Wnt signaling antagonist on the osteoblasts produced by osteocytes, is regulated by mechanical strain and is implicated in the pathogenesis of disuse bone loss. There are no data on sclerostin in humans. Objective: The aim of the study was to evaluate sclerostin in patients immobilized after stroke, compared with control subjects, and to analyze its relationship with markers of bone formation and resorption. Design: This was a cross-sectional study. Setting and patients: We studied 40 postmenopausal women immobilized after a single episode of stroke 6 months or longer after onset, and 40 postmenopausal women from the general community. Bone status was assessed by quantitative ultrasound measurements at the calcaneus. Bone alkaline phosphatase (b-AP), carboxy-terminal telopeptide of type I collagen (CrossLaps), and sclerostin were evaluated by ELISA. We also used ELISA to measure serum levels of Dickkopf-1, another soluble inhibitor of Wnt/β-catenin signaling, highly expressed by ost...

The natural history of benign thyroid nodules.

Abstract: MAIN OUTCOMES AND MEASURES Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up. RESULTS Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer. CONCLUSIONS AND RELEVANCE Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.

Bile duct injury after laparoscopic cholecystectomy: The United States experience

Abstract: Background: Forty series reporting experience with laparoscopic cholecystectomy in the United States from 1989 to 1995 were reviewed A total of 114,005 cases were analyzed and 561 major bile duct injuries (050%) and 401 bile leaks from the cystic duct or liver bed (038%) were recorded Intraoperative cholangiography (IOC) was attempted in 415% of the laparoscopic cholecystectomies and was successful in 827% In major bile duct injuries, the common bile duct/common hepatic duct were the most frequently injured (611%) and only 14% of the patients had complete transection