Latest PUBLICATIONS

  • Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by Differential Inhibition of EGFR Signaling Pathways in Non-Small Cell Lung Cancer.
    Publication Date: 15/11/2015, on Clinical cancer research : an official journal of the American Association for Cancer Research
    by De Rosa V, Iommelli F, Monti M, Fonti R, Votta G, Stoppelli MP, Del Vecchio S
    DOI: 10.1158/1078-0432.CCR-15-0375

    One of the hallmarks of cancer cells is the excessive conversion of glucose to lactate under normoxic conditions, also known as the Warburg effect. Here, we tested whether the targeted inhibition of EGFR may revert this effect and reactivate mitochondrial oxidative phosphorylation in non-small cell lung cancer (NSCLC).

  • Editorial: Further Understanding of Serotonin 7 Receptors' Neuro-psycho-pharmacology.
    Publication Date: 13/11/2015, on Frontiers in behavioral neuroscience
    by Perrone-Capano C, Adriani W
    DOI: 10.3389/fnbeh.2015.00307

  • Aptamer targeting EGFRvIII mutant hampers its constitutive autophosphorylation and affects migration, invasion and proliferation of glioblastoma cells.
    Publication Date: 10/11/2015, on Oncotarget
    by Camorani S, Crescenzi E, Colecchia D, Carpentieri A, Amoresano A, Fedele M, Chiariello M, Cerchia L
    DOI: 10.18632/oncotarget.6066

    Glioblastoma Multiforme (GBM) is the most common and aggressive human brain tumor, associated with very poor survival despite surgery, radiotherapy and chemotherapy.The epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor β (PDGFRβ) are hallmarks in GBM with driving roles in tumor progression. In approximately half of the tumors with amplified EGFR, the EGFRvIII truncated extracellular mutant is detected. EGFRvIII does not bind ligands, is highly oncogenic and its expression confers resistance to EGFR tyrosine kinase inhibitors (TKIs). It has been demonstrated that EGFRvIII-dependent cancers may escape targeted therapy by developing dependence on PDGFRβ signaling, thus providing a strong rationale for combination therapy aimed at blocking both EGFRvIII and PDGFRβsignaling.We have recently generated two nuclease resistant RNA aptamers, CL4 and Gint4.T, as high affinity ligands and inhibitors of the human wild-type EGFR (EGFRwt) and PDGFRβ, respectively.Herein, by different approaches, we demonstrate that CL4 aptamer binds to the EGFRvIII mutant even though it lacks most of the extracellular domain. As a consequence of binding, the aptamer inhibits EGFRvIII autophosphorylation and downstream signaling pathways, thus affecting migration, invasion and proliferation of EGFRvIII-expressing GBM cell lines.Further, we show that targeting EGFRvIII by CL4, as well as by EGFR-TKIs, erlotinib and gefitinib, causes upregulation of PDGFRβ. Importantly, CL4 and gefitinib cooperate with the anti-PDGFRβ Gint4.T aptamer in inhibiting cell proliferation.The proposed aptamer-based strategy could have impact on targeted molecular cancer therapies and may result in progresses against GBMs.

  • Analysis of the role of O-glycosylation in GH51 α-L-arabinofuranosidase from Pleurotus ostreatus.
    Publication Date: 01/11/2015, on Biotechnology and applied biochemistry
    by Amore A, Serpico A, Amoresano A, Vinciguerra R, Faraco V
    DOI: 10.1002/bab.1325

    In this study, the recombinant α-L-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis with the aim of elucidating the role of glycosylation on the properties of the enzyme at the level of S160 residue. As a matter of fact, previous mass spectral analyses had led to the localization of a single O-glycosylation at this site. Recombinant expression and characterization of the rPoAbf mutant S160G was therefore performed. It was shown that the catalytic properties are slightly changed by the mutation, with a more evident modification of the Kcat and KM toward the synthetic substrate pN-glucopyranoside. More importantly, the mutation negatively affected the stability of the enzyme at various pHs and temperatures. Circular dichroism (CD) analyses showed a minimum at 210 nm for wild-type (wt) rPoAbf, typical of the beta-sheets structure, whereas this minimum is shifted for rPoAbf S160G, suggesting the presence of an unfolded structure. A similar behavior was revealed when wt rPoAbf was enzymatically deglycosylated. CD structural analyses of both the site-directed mutant and the enzymatically deglycosylated wild-type enzyme indicate a role of the glycosylation at the S160 residue in rPoAbf secondary structure stability.

  • Hormonal regulation and characterization of MHG30 gene, a desaturase-like gene of hamster harderian gland.
    Publication Date: 01/11/2015, on The Journal of steroid biochemistry and molecular biology
    by Esposito T, Tammaro P, Paolisso G, Varriale B
    DOI: 10.1016/j.jsbmb.2015.07.010

    The harderian gland (HG) is an orbital gland of the vast majority of land vertebrates. In the Syrian hamster these glands display a marked sexual dimorphism. Here we present data on a male specific clone named MHG30. The MHG30 cDNA (1470 bp) has significant sequence homologies with human #15μ10#Δ6-desaturase enzymes. The expression of MHG30 has been found in male HG and in the liver of both sexes, no other tissue showing the presence of MHG30 mRNA. Castration brings the MHG30 levels below detectable level in about 7 days. In in vitro cultures of male hamster HG cells, androgens (A) determine an enhancement of MHG30 expression in a time-dependent manner. Conversely, a continuous decrement has been observed in control cells and in cells treated with A plus flutamide (F) or with A and cycloheximide (Cy). Incubation of cells in cultures supplemented with desamethason (Dex) or thyroid hormone (T3) also increases MHG30 expression while 17β-estradiol prevents the stimulatory effect exerted by A, Dex and T3. Findings strongly suggest that the MHG30 gene could be involved in supporting the sexual dimorphism and its expression is likely triggered by a series of hormonal interactions.

  • Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis.
    Publication Date: 01/11/2015, on Brain : a journal of neurology
    by Iaffaldano P, Lucisano G, Pozzilli C, Brescia Morra V, Ghezzi A, Millefiorini E, Patti F, Lugaresi A, Zimatore GB, Marrosu MG, Amato MP, Bertolotto A, Bergamaschi R, Granella F, Coniglio G, Tedeschi G, Sola P, Lus G, Ferrò MT, Iuliano G, Corea F, Protti A, Cavalla P, Guareschi A, Rodegher M, Paolicelli D, Tortorella C, Lepore V, Prosperini L, Saccà F, Baroncini D, Comi G, Trojano M,
    DOI: 10.1093/brain/awv260

    The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.

  • Cerebral Involvement in Stargardt's Disease: A VBM and TBSS Study.
    Publication Date: 01/11/2015, on Investigative ophthalmology & visual science
    by Olivo G, Melillo P, Cocozza S, D'Alterio FM, Prinster A, Testa F, Brunetti A, Simonelli F, Quarantelli M
    DOI: 10.1167/iovs.15-16899

    To assess whether and to what extent macro- and/or microstructural modifications are present in the brain of patients with selective central visual loss due to a juvenile macular degeneration, Stargardt's disease (STGD), taking advantage of the complementary information provided by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

  • Ocriplasmin use in a selected case with preserved visual acuity.
    Publication Date: 29/10/2015, on BMC ophthalmology
    by Rossi S, Orrico A, Melillo P, Testa F, Simonelli F, Della Corte M
    DOI: 10.1186/s12886-015-0141-9

    Previous studies described cases of Ocriplasmin injections in patients with vitreo-macular traction and reduced central visual acuity. We describe the first case of a patient with 20/20 visual acuity and vitreo-macular traction treated with Ocriplasmin, and, for the first time in literature, we evaluated the functional changes of the macula in response to pharmacological treatment through multifocal-electroretinogram.

  • Deglycosylation Step to Improve the Identification of Egg Proteins in Art Samples.
    Publication Date: 20/10/2015, on Analytical chemistry
    by Vinciguerra R, Galano E, Vallone F, Greco G, Vergara A, Bonaduce I, Marino G, Pucci P, Amoresano A, Birolo L
    DOI: 10.1021/acs.analchem.5b02423

    A deglycosylation step using Peptide-N-Glycosidase F (PNGaseF) has been introduced in a standard proteomic protocol to more confidently identify egg based binders. The ingenuity of introducing a PNGaseF digestion was aimed at removing the molecular hindrance, made up by the heavily glycosylated egg proteins, before the protease(s) hydrolysis. This novelty in the protocol resulted in obtaining a significant increase of proteolytic egg peptides thus improving the quality and reliability of egg identification in artwork samples. The protocol has been set up on paint replicas and successfully tested on two historical samples of different origin.

  • Serratiopeptidase: a well-known metalloprotease with a new non-proteolytic activity against S. aureus biofilm.
    Publication Date: 09/10/2015, on BMC microbiology
    by Selan L, Papa R, Tilotta M, Vrenna G, Carpentieri A, Amoresano A, Pucci P, Artini M
    DOI: 10.1186/s12866-015-0548-8

    The use of indwelling medical devices is associated with a significant risk of infections by Staphylococcus aureus (S. aureus) which possesses a variety of virulence factors including many toxins and the ability to invade eukaryotic cells or to form biofilm on biotic and abiotic surfaces. The virulence factors above described are often related to proteins exposed on the bacterial surface. Blocking S. aureus colonization may reduce the incidence of invasive infectious diseases. Previously reports evaluated the anti-infective properties of serratiopeptidase (Spep), an extracellular metalloprotease produced by Serratia marcescens ATCC 21074 (E-15), in impairing virulence-related staphylococcal properties, such as attachment to inert surfaces and adhesion/invasion on eukaryotic cells. However, to date its mechanism of action is unknown.

  • Mild Cognitive Impairment in newly diagnosed Parkinson's disease: A longitudinal prospective study.
    Publication Date: 01/10/2015, on Parkinsonism & related disorders
    by Santangelo G, Vitale C, Picillo M, Moccia M, Cuoco S, Longo K, Pezzella D, di Grazia A, Erro R, Pellecchia MT, Amboni M, Trojano L, Barone P
    DOI: 10.1016/j.parkreldis.2015.08.024

    In PD, Mild Cognitive Impairment (PD-MCI) occurs since early stages of disease. The aims were to assess presence of PD-MCI in untreated, drug-naive PD patients, and to follow-up the sample over 4 years to ascertain evolution of neurocognitive profile.

  • An Italian multicentre validation study of the coma recovery scale-revised.
    Publication Date: 01/10/2015, on European journal of physical and rehabilitation medicine
    by Estraneo A, Moretta P, De Tanti A, Gatta G, Giacino JT, Trojano L,
    DOI:

    Rate of misdiagnosis of disorders of consciousness (DoC) can be reduced by employing validated clinical diagnostic tools, such as the Coma Recovery Scale-Revised (CRS-R). An Italian version of the CRS-R has been recently developed, but its applicability across different clinical settings, and its concurrent validity and diagnostic sensitivity have not been estimated yet.

  • Walking indoors, walking outdoors: an fMRI study.
    Publication Date: 01/10/2015, on Frontiers in psychology
    by Dalla Volta R, Fasano F, Cerasa A, Mangone G, Quattrone A, Buccino G
    DOI: 10.3389/fpsyg.2015.01502

    An observation/execution matching system for walking has not been assessed yet. The present fMRI study was aimed at assessing whether, as for object-directed actions, an observation/execution matching system is active for walking and whether the spatial context of walking (open or narrow space) recruits different neural correlates. Two experimental conditions were employed. In the execution condition, while being scanned, participants performed walking on a rolling cylinder located just outside the scanner. The same action was performed also while observing a video presenting either an open space (a country field) or a narrow space (a corridor). In the observation condition, participants observed a video presenting an individual walking on the same cylinder on which the actual action was executed, the open space video and the narrow space video, respectively. Results showed common bilateral activations in the dorsal premotor/supplementary motor areas and in the posterior parietal lobe for both execution and observation of walking, thus supporting a matching system for this action. Moreover, specific sectors of the occipital-temporal cortex and the middle temporal gyrus were consistently active when processing a narrow space versus an open one, thus suggesting their involvement in the visuo-motor transformation required when walking in a narrow space. We forward that the present findings may have implications for rehabilitation of gait and sport training.

  • Impaired healing of fragility fractures in type 2 diabetes: clinical and radiographic assessments and serum cytokine levels.
    Publication Date: 01/10/2015, on Aging clinical and experimental research
    by Liuni FM, Rugiero C, Feola M, Rao C, Pistillo P, Terracciano C, Giganti MG, Tarantino U
    DOI: 10.1007/s40520-015-0422-4

    Diabetes induces bone alterations accompanied by altered cytokine expression patterns. These alterations lead to modified fracture healing, contributing to musculoskeletal fragility in the elderly.

  • Cloud-Based Smart Health Monitoring System for Automatic Cardiovascular and Fall Risk Assessment in Hypertensive Patients.
    Publication Date: 01/10/2015, on Journal of medical systems
    by Melillo P, Orrico A, Scala P, Crispino F, Pecchia L
    DOI: 10.1007/s10916-015-0294-3

    The aim of this paper is to describe the design and the preliminary validation of a platform developed to collect and automatically analyze biomedical signals for risk assessment of vascular events and falls in hypertensive patients. This m-health platform, based on cloud computing, was designed to be flexible, extensible, and transparent, and to provide proactive remote monitoring via data-mining functionalities. A retrospective study was conducted to train and test the platform. The developed system was able to predict a future vascular event within the next 12 months with an accuracy rate of 84 % and to identify fallers with an accuracy rate of 72 %. In an ongoing prospective trial, almost all the recruited patients accepted favorably the system with a limited rate of inadherences causing data losses (<20 %). The developed platform supported clinical decision by processing tele-monitored data and providing quick and accurate risk assessment of vascular events and falls.