Latest PUBLICATIONS

  • Management of QT prolongation induced by anti-cancer drugs: Target therapy and old agents. Different algorithms for different drugs.
    Publication Date: 06/12/2017, on Cancer treatment reviews
    by Coppola C, Rienzo A, Piscopo G, Barbieri A, Arra C, Maurea N
    DOI: 10.1016/j.ctrv.2017.11.009

    The side effects of anticancer drugs still play a critical role in survival and quality of life. Although the recent progresses of cancer therapies have significantly improved the prognosis of oncologic patients, side effects of antineoplastic treatments are still responsible for the increased mortality of cancer survivors. Cardiovascular toxicity is the most dangerous adverse effect induced by anticancer therapies. A survey conducted by the National Health and Nutrition Examination, showed that 1807 cancer survivors followed up for seven years: 51% died of cancer and 33% of heart disease (Vejpongsa and Yeh, 2014). Moreover, the risk of cardiotoxicity persists even with the targeted therapy, the newer type of cancer treatment, due to the presence of on-target and off-target effects related to this new class of drugs. The potential cardiovascular toxicity of anticancer agents includes: QT prolongation, arrhythmias, myocardial ischemia, stroke, hypertension (HTN), thromboembolism, left ventricular dysfunction and heart failure (HF). Compared to other cardiovascular disorders, the interest in QT prolongation and its complications is fairly recent. However, oncologists have to deal with it and to evaluate the risk-benefit ratio before starting the treatment or during the same. Electrolyte abnormalities, low levels of serum potassium and several drugs may favour the acquired QT prolongation. Treatment of marked QT prolongation includes cardiac monitoring, caution in the use or suspension of cancer drugs and correction of electrolyte abnormalities (hypokalaemia, hypomagnesaemia, hypocalcaemia). Syndrome of QT prolongation can be associated with potentially fatal cardiac arrhythmias and its treatment consists of intravenous administration of magnesium sulphate and the use of electrical cardioversion.

  • Triple Vectors Expand AAV Transfer Capacity in the Retina.
    Publication Date: 05/12/2017, on Molecular therapy : the journal of the American Society of Gene Therapy
    by Maddalena A, Tornabene P, Tiberi P, Minopoli R, Manfredi A, Mutarelli M, Rossi S, Simonelli F, Naggert JK, Cacchiarelli D, Auricchio A
    DOI: 10.1016/j.ymthe.2017.11.019

    Retinal gene transfer with adeno-associated viral (AAV) vectors holds great promise for the treatment of inherited retinal degenerations (IRDs). One limit of AAV is its transfer capacity of about 5 kb, which can be expanded to about 9 kb, using dual AAV vectors. This strategy would still not suffice for treatment of IRDs such as Usher syndrome type 1D or Alström syndrome type I (ALMS) due to mutations in CDH23 or ALMS1, respectively. To overcome this limitation, we generated triple AAV vectors, with a maximal transfer capacity of about 14 kb. Transcriptomic analysis following triple AAV transduction showed the expected full-length products along a number of aberrant transcripts. However, only the full-length transcripts are efficiently translated in vivo. We additionally showed that approximately 4% of mouse photoreceptors are transduced by triple AAV vectors and showed correct localization of recombinant ALMS1. The low-photoreceptor transduction levels might justify the modest and transient improvement we observe in the retina of a mouse model of ALMS. However, the levels of transduction mediated by triple AAV vectors in pig retina reached 40% of those observed with single vectors, and this bodes well for further improving the efficiency of triple AAV vectors in the retina.

  • The Closing-In Phenomenon in an Ecological Walking Task.
    Publication Date: 04/12/2017, on Journal of the International Neuropsychological Society : JINS
    by De Lucia N, Grossi D, Milan G, Trojano L
    DOI: 10.1017/S1355617717001229

    Alzheimer's disease (AD) patients may show the Closing-in (CI), a tendency to reproduce figures close to or superimposed on the model. AD patients with CI might manifest reduced functional independence compared to AD patients without CI, but no study directly assessed if CI can hamper common daily living activities. To address this issue here we investigated whether AD patients with CI veer their walking trajectory toward irrelevant objects more often than AD patients without CI.

  • Editorial: Novel Mechanism of Radioactive Iodine Refractivity in Thyroid Cancer.
    Publication Date: 01/12/2017, on Journal of the National Cancer Institute
    by Paladino S, Melillo RM
    DOI: 10.1093/jnci/djx106

  • Diagnostic contribution of magnetic resonance imaging in an atypical presentation of motor neuron disease.
    Publication Date: 01/12/2017, on Quantitative imaging in medicine and surgery
    by Ugga L, Coppola C, Cocozza S, Saracino D, Caranci F, Tuccillo F, Signoriello E, Casertano S, Di Iorio G, Tedeschi E
    DOI: 10.21037/qims.2017.10.06

    Motor neuron disease (MND) is a neurodegenerative disease determining progressive and relentless motor deterioration involving both upper and lower motor neurons (UMN and LMN); several variants at onset are described. Here we describe a case of MND presenting as pure spastic monoparesis in which magnetic resonance imaging (MRI) gave a substantial contribution in confirming the diagnosis and assessing the severity of UMN involvement. An isolated pyramidal syndrome, with complete absence of LMN signs, is a rare phenotype in the context of MND (less than 4% of total cases), especially if restricted to only one limb. Several other elements made this case an unusual presentation of MND: the late age of onset (8th decade), the subacute evolution of symptoms (raising the suspicion of an ischemic or inflammatory, rather than degenerative, etiology), the patient's past medical history (achalasia, erythema nodosum), the increase of inflammatory indices. Conventional MRI showed no focal lesions that could explain the clinical features; therefore, we used advanced MR sequences. Diffusion tensor imaging (DTI) evaluation evidenced bilateral impairment of corticospinal tract (CST) diffusion metrics, with clear right-left asymmetry, pointing to a neurodegenerative etiology, which clinically appeared less likely at that time. Magnetic resonance spectroscopy (MRS) showed a significant reduction of NAA/Cho + Cr ratio in the motor cortex (MC), further supporting the hypothesis of UMN degeneration. In conclusion, in this particular case of MND, whose nosographic framing has not been fully defined, advanced MRI techniques with DTI and MRS proved to be of great usefulness in confirming a diffuse UMN involvement, possibly at a more advanced stage than its clinical expression.

  • GPI-anchored proteins are confined in subdiffraction clusters at the apical surface of polarized epithelial cells.
    Publication Date: 01/12/2017, on The Biochemical journal
    by Paladino S, Lebreton S, Lelek M, Riccio P, De Nicola S, Zimmer C, Zurzolo C
    DOI: 10.1042/BCJ20170582

    Spatio-temporal compartmentalization of membrane proteins is critical for the regulation of diverse vital functions in eukaryotic cells. It was previously shown that, at the apical surface of polarized MDCK cells, glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are organized in small cholesterol-independent clusters of single GPI-AP species (homoclusters), which are required for the formation of larger cholesterol-dependent clusters formed by multiple GPI-AP species (heteroclusters). This clustered organization is crucial for the biological activities of GPI-APs; hence, understanding the spatio-temporal properties of their membrane organization is of fundamental importance. Here, by using direct stochastic optical reconstruction microscopy coupled to pair correlation analysis (pc-STORM), we were able to visualize and measure the size of these clusters. Specifically, we show that they are non-randomly distributed and have an average size of 67 nm. We also demonstrated that polarized MDCK and non-polarized CHO cells have similar cluster distribution and size, but different sensitivity to cholesterol depletion. Finally, we derived a model that allowed a quantitative characterization of the cluster organization of GPI-APs at the apical surface of polarized MDCK cells for the first time. Experimental FRET (fluorescence resonance energy transfer)/FLIM (fluorescence-lifetime imaging microscopy) data were correlated to the theoretical predictions of the model.

  • Motor, behavioural, and cognitive correlates of fatigue in early, de novo Parkinson disease patients.
    Publication Date: 01/12/2017, on Parkinsonism & related disorders
    by Siciliano M, Trojano L, De Micco R, De Mase A, Garramone F, Russo A, Tedeschi G, Tessitore A
    DOI: 10.1016/j.parkreldis.2017.10.004

    Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.

  • Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study.
    Publication Date: 28/11/2017, on Neurology
    by Laroni A, Signori A, Maniscalco GT, Lanzillo R, Russo CV, Binello E, Lo Fermo S, Repice A, Annovazzi P, Bonavita S, Clerico M, Baroncini D, Prosperini L, La Gioia S, Rossi S, Cocco E, Frau J, Torri Clerici V, Signoriello E, Sartori A, Zarbo IR, Rasia S, Cordioli C, Cerqua R, Di Sapio A, Lavorgna L, Pontecorvo S, Barrilà C, Saccà F, Frigeni B, Esposito S, Ippolito D, Gallo F, Sormani MP,
    DOI: 10.1212/WNL.0000000000004686

    To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.

  • Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques.
    Publication Date: 28/11/2017, on International ophthalmology
    by Rossi S, Santamaria C, Boccia R, De Rosa L, D'Alterio FM, Simonelli F, De Rosa G
    DOI: 10.1007/s10792-017-0772-3

    To evaluate the clinical results of standard, transepithelial (TE) and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive keratoconus.

  • Bisphenol A and Bisphenol S release in milk under household conditions from baby bottles marketed in Italy.
    Publication Date: 27/11/2017, on Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes
    by Russo G, Barbato F, Cardone E, Fattore M, Albrizio S, Grumetto L
    DOI: 10.1080/03601234.2017.1388662

    A simple and sensitive validated analytical method based on liquid chromatography coupled to tandem fluorescence (FD) and ultraviolet (UV) spectrophotometry was applied to monitor the presence of bisphenol A and bisphenol S in plastic baby bottles marketed in Italy. The limits of detection (LOD) were 3.75 ng mL-1 and 80.00 ng mL-1, and those of quantification (LOQ) were 12.51 ng mL-1 and 260.00 ng mL-1 for BPA (FD detection) and for BPS (UV detection), respectively. BPA was found in only four samples, two samples undergone to microwave heating and two samples undergone to bottle warmer heating either at 40°C or at 80°C. Although the quantities of leached BPA were well below the reference dose for daily intake established by the European Food Safety Authority (EFSA) (4.0 µg kg-1 bw/day), the release of BPA and BPS from these plastic materials should be carefully considered by the government authorities to increase people's awareness on this issue and to protect the most vulnerable population group.

  • Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.
    Publication Date: 03/11/2017, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Cardinale A, Fusco FR, Paldino E, Giampà C, Marino M, Nuzzo MT, D'Angelo V, Laurenti D, Straccia G, Fasano D, Sarnataro D, Squillaro T, Paladino S, Melone MAB
    DOI: 10.1007/s10072-017-3168-2

    Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

  • Probing the Eumelanin-Silica Interface in Chemically Engineered Bulk Hybrid Nanoparticles for Targeted Subcellular Antioxidant Protection.
    Publication Date: 01/11/2017, on ACS applied materials & interfaces
    by Silvestri B, Vitiello G, Luciani G, Calcagno V, Costantini A, Gallo M, Parisi S, Paladino S, Iacomino M, D'Errico G, Caso MF, Pezzella A, d'Ischia M
    DOI: 10.1021/acsami.7b11839

    We disclose herein the first example of stable monodispersed hybrid nanoparticles (termed MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a silica nanoscaffold matrix and endowed with high antioxidant and cytoprotective effects associated with a specific subcellular localization. MelaSil-NPs have been fabricated by an optimized sol-gel methodology involving ammonia-induced oxidative polymerization of a covalent conjugate of the eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA) with 3-aminopropyltriethoxysilanes (APTS). They displayed a round-shaped (ca. 50-80 nm) morphology, exhibited the typical electron paramagnetic resonance signal of eumelanin biopolymers, and proved effective in promoting decomposition of hydrogen peroxide under physiologically relevant conditions. When administered to human ovarian cancer cells (A2780) or cervical cancer cells (HeLa), MelaSil-NPs were rapidly internalized and colocalized with lysosomes and exerted efficient protecting effects against hydrogen peroxide-induced oxidative stress and cytotoxicity.

  • Antitumour activity of resveratrol on human melanoma cells: A possible mechanism related to its interaction with malignant cell telomerase.
    Publication Date: 01/11/2017, on Biochimica et biophysica acta
    by Platella C, Guida S, Bonmassar L, Aquino A, Bonmassar E, Ravagnan G, Montesarchio D, Roviello GN, Musumeci D, Fuggetta MP
    DOI: 10.1016/j.bbagen.2017.08.001

    trans-Resveratrol (tRES) is a polyphenolic stilbene found in plant products which has attracted great attention because of its antioxidant, anti-inflammatory and anticancer properties.

  • Binding of Harmine Derivatives to DNA: A Spectroscopic Investigation.
    Publication Date: 27/10/2017, on Molecules (Basel, Switzerland)
    by Pagano B, Caterino M, Filosa R, Giancola C
    DOI: 10.3390/molecules22111831

    Harmine belongs to a group of β-carboline alkaloids endowed with antitumor properties. Harmine and its derivatives are thought to bind to DNA and interfere with topoisomerase activities. We investigated the base-dependent binding of harmine, and three of its synthetic anticancer-active derivatives to the genomic DNA from calf thymus and two synthetic 20-mer double helices, the poly(dG-dC)·poly(dG-dC) and the poly(dA-dT)·poly(dA-dT), by means of UV-Vis and circular dichroism (CD) spectroscopies. The data show that the DNA binding and stabilising properties of the investigated derivatives are base pair-dependent. These results could be used as a guide to design and develop further bioactive analogues.

  • Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences.
    Publication Date: 26/10/2017, on Oncogene
    by Valentino A, Calarco A, Di Salle A, Finicelli M, Crispi S, Calogero RA, Riccardo F, Sciarra A, Gentilucci A, Galderisi U, Margarucci S, Peluso G
    DOI: 10.1038/onc.2017.216

    Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.