Latest PUBLICATIONS

  • Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test in western countries.
    Publication Date: 01/12/2014, on The Pediatric infectious disease journal
    by Chiappini E, Bonsignori F, Mazzantini R, Sollai S, Venturini E, Mangone G, Cortimiglia M, Olivito B, Azzari C, Galli L, de Martino M
    DOI: 10.1097/INF.0000000000000432

    Tuberculin skin test, QuantiFERON-TB Gold In-Tube and T-SPOT.TB were performed in 338 children at risk for tuberculosis (TB), including 70 active TB cases. In children <5 years of age, QuantiFERON-TB Gold In-Tube sensitivity was 73.3% [95% confidence interval (CI): 57.5-89.1]; and T-SPOT.TB sensitivity was 59.3% (95% CI: 40.1-77.8); both were inferior to tuberculin skin test sensitivity (90.0%; 95% CI: 79.3-100). In children ≥ 5 years QuantiFERON-TB Gold In-Tube sensitivity was 92.5% (95% CI: 84.4-100); T-SPOT.TB sensitivity was 73.0% (95% CI: 58.6-87.3) ; and tuberculin skin test sensitivity was 97.5% (95% CI: 92.6-100).Test specificities were similar in all age groups.

  • Macular function and morphologic features in juvenile stargardt disease: longitudinal study.
    Publication Date: 01/12/2014, on Ophthalmology
    by Testa F, Melillo P, Di Iorio V, Orrico A, Attanasio M, Rossi S, Simonelli F
    DOI: 10.1016/j.ophtha.2014.06.032

    To evaluate disease progression in a cohort of patients with a clinical and genetic diagnosis of Stargardt disease.

  • Foix-Chavany-Marie syndrome in a 17-year-old female with congenital cytomegalovirus infection.
    Publication Date: 20/11/2014, on Neuropsychiatric disease and treatment
    by Conforti R, Capasso R, Capaldo G, Dato C, Saracino D, Di Iorio G, Melone MA
    DOI: 10.2147/NDT.S68098

    Foix-Chavany-Marie syndrome is characterized by bilateral facio-glosso-pharyngo-masticatory paralysis of voluntary movement due to bilateral anterior opercular lesions. We describe the case of a 17-year-old female affected by Foix-Chavany-Marie syndrome and congenital cytomegalovirus infection, evaluating the possible etiopathogenetic correlation between cerebral cortical dysplasia and intrauterine infections.

  • Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid.
    Publication Date: 15/11/2014, on Oncotarget
    by Porru M, Zappavigna S, Salzano G, Luce A, Stoppacciaro A, Balestrieri ML, Artuso S, Lusa S, De Rosa G, Leonetti C, Caraglia M
    DOI: 10.18632/oncotarget.2182

    Glioblastomas are highly aggressive adult brain tumors with poor clinical outcome. In the central nervous system (CNS) the blood-brain barrier (BBB) is the most important limiting factor for both development of new drugs and drug delivery. Here, we propose a new strategy to treat glioblastoma based on transferrin (Tf)-targeted self-assembled nanoparticles (NPs) incorporating zoledronic acid (ZOL) (NPs-ZOL-Tf). NPs-ZOL-Tf have been assessed on the glioblastoma cell line U373MG-LUC that showed a refractoriness in vitro to temozolomide (TMZ) and fotemustine (FTM). NPs-ZOL-Tf treatment resulted in higher in vitro cytotoxic activity than free ZOL. However, the potentiation of anti-proliferative activity of NPs-ZOL-Tf was superimposable to that one induced by NPs-ZOL (not armed with Tf). On the other hand, NPs-ZOL-Tf showed a higher antitumor efficacy if compared with that one caused by NPs-ZOL in immunosuppressed mice intramuscularly bearing U373MG-LUC xenografts, inducing a significant tumor weight inhibition (TWI). The experiments performed on mice with intracranial U373MG-LUC xenografts confirmed the efficacy of NPs-ZOL-Tf. These effects were paralleled by a higher intratumour localization of fluorescently-labeled-NPs-Tf both in intramuscular and intracranial xenografts. In conclusion, our results demonstrate that the encapsulation of ZOL increases the antitumor efficacy of this drug in glioblastoma through the acquisition of ability to cross the BBB.

  • Polyketide synthases in the microbiome of the marine sponge Plakortis halichondrioides: a metagenomic update.
    Publication Date: 14/11/2014, on Marine drugs
    by Della Sala G, Hochmuth T, Teta R, Costantino V, Mangoni A
    DOI: 10.3390/md12115425

    Sponge-associated microorganisms are able to assemble the complex machinery for the production of secondary metabolites such as polyketides, the most important class of marine natural products from a drug discovery perspective. A comprehensive overview of polyketide biosynthetic genes of the sponge Plakortis halichondrioides and its symbionts was obtained in the present study by massively parallel 454 pyrosequencing of complex and heterogeneous PCR (Polymerase Chain Reaction) products amplified from the metagenomic DNA of a specimen of P. halichondrioides collected in the Caribbean Sea. This was accompanied by a survey of the bacterial diversity within the sponge. In line with previous studies, sequences belonging to supA and swfA, two widespread sponge-specific groups of polyketide synthase (PKS) genes were dominant. While they have been previously reported as belonging to Poribacteria (a novel bacterial phylum found exclusively in sponges), re-examination of current genomic sequencing data showed supA and swfA not to be present in the poribacterial genome. Several non-supA, non-swfA type-I PKS fragments were also identified. A significant portion of these fragments resembled type-I PKSs from protists, suggesting that bacteria may not be the only source of polyketides from P. halichondrioides, and that protistan PKSs should receive further investigation as a source of novel polyketides.

  • Simplexide induces CD1d-dependent cytokine and chemokine production from human monocytes.
    Publication Date: 12/11/2014, on PloS one
    by Loffredo S, Staiano RI, Granata F, Costantino V, Borriello F, Frattini A, Lepore MT, Mangoni A, Marone G, Triggiani M
    DOI: 10.1371/journal.pone.0111326

    Monocytes are major effector cells of innate immunity and recognize several endogenous and exogenous molecules due to the expression of wide spectrum of receptors. Among them, the MHC class I-like molecule CD1d interacts with glycolipids and presents them to iNKT cells, mediating their activation. Simplexide belongs to a novel class of glycolipids isolated from marine sponges and is structurally distinct from other immunologically active glycolipids. In this study we have examined the effects of simplexide on cytokine and chemokine release from human monocytes. Simplexide induces a concentration- and time-dependent release of IL-6, CXCL8, TNF-α and IL-10 and increases the expression of IL6, CXCL8 and IL10 mRNA. Cytokine and chemokine release induced by simplexide from monocytes is dependent on CD1d since: i) a CD1d antagonist, 1,2-bis (diphenylphosphino) ethane [DPPE]-polyethylene glycolmonomethylether [PEG], specifically blocks simplexide-induced activation of monocytes; ii) CD1d knockdown inhibits monocyte activation by simplexide and iii) simplexide induces cytokine production from CD1d-transfected but not parental C1R cell line. Finally, we have shown that simplexide also induces iNKT cell expansion in vitro. Our results demonstrate that simplexide, apart from activating iNKT cells, induces the production of cytokines and chemokines from human monocytes by direct interaction with CD1d.

  • Biologically enabled sub-diffractive focusing.
    Publication Date: 03/11/2014, on Optics express
    by De Tommasi E, De Luca AC, Lavanga L, Dardano P, De Stefano M, De Stefano L, Langella C, Rendina I, Dholakia K, Mazilu M
    DOI: 10.1364/OE.22.027214

    Evolution shows that photonic structures are a constituent part of many animals and flora. These elements produce structural color and are useful in predator-prey interactions between animals and in the exploitation of light for photosynthetic organisms. In particular, diatoms have evolved patterned hydrated silica external valves able to confine light with extraordinary efficiency. Their evolution was probably guided by the necessity to survive in harsh conditions of sunlight deprivation. Here, we exploit such diatom valves, in conjunction with structured illumination, to realize a biological super-resolving lens to achieve sub-diffractive focusing in the far field. More precisely, we consider a single diatom valve of Arachnoidiscus genus which shows symmetries and fine features. By characterizing and using the transmission properties of this valve using the optical eigenmode technique, we are able to confine light to a tiny spot with unprecedented precision in terms of resolution limit ratio, corresponding in this case to 0.21λ/NA.

  • Hepatocellular carcinoma invading portal venous system in cirrhosis: long-term results of percutaneous radiofrequency ablation of both the nodule and portal vein tumor thrombus. A case control study.
    Publication Date: 01/11/2014, on Anticancer research
    by Giorgio A, Calisti G, Montesarchio L, Scognamiglio U, Matteucci P, Coppola C, Scarano F, Amendola F, Giorgio V
    DOI:

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Portal vein tumor thrombus (PVTT) is one of the most dreadful complications of HCC and is associated with a median survival time of 2.7-4.0 months. The optimal treatment for HCC with PVTT has not yet been established. The aim of the present study was to report long-term results of percutaneous radiofrequency (RF) ablation of both HCC single nodule (up to 5 cm in diameter) and neoplastic main portal vein thrombus, compared to no-treatment.

  • Unusual Stüve-Wiedemann syndrome with complete maternal chromosome 5 isodisomy.
    Publication Date: 01/11/2014, on Annals of clinical and translational neurology
    by Melone MA, Pellegrino MJ, Nolano M, Habecker BA, Johansson S, Nathanson NM, Knappskog PM, Hahn AF, Boman H
    DOI: 10.1002/acn3.126

    A woman was isozygous for a novel mutation in the leukemia inhibitory factor receptor gene (LIFR) (c.2170C>G; p.Pro724Ala) which disrupts LIFR downstream signaling and results in Stüve-Wiedemann syndrome (STWS). She inherited two identical chromosomes 5 from her mother, heterozygous for the LIFR mutation. The presentation was typical for STWS, except there was no long bone dysplasia. Prominent cold-induced sweating and heat intolerance lead to an initial diagnosis of cold-induced sweating syndrome, excluded by exome sequencing. Skin biopsies provide the first human evidence of failed postnatal cholinergic differentiation of sympathetic neurons innervating sweat glands in cold-induced sweating, and of a neuropathy.

  • Brain synaptosomes harbor more than one cytoplasmic system of protein synthesis.
    Publication Date: 01/11/2014, on Journal of neuroscience research
    by Cefaliello C, Eyman M, Melck D, De Stefano R, Ferrara E, Crispino M, Giuditta A
    DOI: 10.1002/jnr.23435

    Synaptosomal protein synthesis from rat brain is selectively increased by learning and is massively enhanced during the recovery period from brain ischemia. To lay the groundwork for identification of the involved synaptic elements, we examined the effects induced by varying the concentrations of extracellular cations and endogenous calcium. Most of the recorded rate response curves exhibited biphasic profiles that suggested the presence of more than one translation system. Because comparable profiles were obtained by fully inhibiting mitochondrial translation, the data indicated the involvement of cytoplasmic translation systems present in different synaptosomal classes. Their properties may be individually investigated by exploiting the partially inhibited conditions we have described. The identification of the synaptic elements from which they originated and their newly synthesized proteins will significantly expand our understanding of the synaptic contribution to brain plastic events.

  • Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence.
    Publication Date: 30/10/2014, on Oncotarget
    by Finicelli M, Benedetti G, Squillaro T, Pistilli B, Marcellusi A, Mariani P, Santinelli A, Latini L, Galderisi U, Giordano A
    DOI: 10.18632/oncotarget.1936

    The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.

  • Neuronal differentiation dictates estrogen-dependent survival and ERK1/2 kinetic by means of caveolin-1.
    Publication Date: 28/10/2014, on PloS one
    by Volpicelli F, Caiazzo M, Moncharmont B, di Porzio U, Colucci-D'Amato L
    DOI: 10.1371/journal.pone.0109671

    Estrogens promote a plethora of effects in the CNS that profoundly affect both its development and mature functions and are able to influence proliferation, differentiation, survival and neurotransmission. The biological effects of estrogens are cell-context specific and also depend on differentiation and/or proliferation status in a given cell type. Furthermore, estrogens activate ERK1/2 in a variety of cellular types. Here, we investigated whether ERK1/2 activation might be influenced by estrogens stimulation according to the differentiation status and the molecular mechanisms underling this phenomenon. ERK1/2 exert an opposing role on survival and death, as well as on proliferation and differentiation depending on different kinetics of phosphorylation. Hence we report that mesencephalic primary cultures and the immortalized cell line mes-c-myc A1 express estrogen receptor α and activate ERK1/2 upon E2 stimulation. Interestingly, following the arrest of proliferation and the onset of differentiation, we observe a change in the kinetic of ERKs phosphorylation induced by estrogens stimulation. Moreover, caveolin-1, a main constituent of caveolae, endogenously expressed and co-localized with ER-α on plasma membrane, is consistently up-regulated following differentiation and cell growth arrest. In addition, we demonstrate that siRNA-induced caveolin-1 down-regulation or disruption by means of ß-cyclodextrin treatment changes ERK1/2 phosphorylation in response to estrogens stimulation. Finally, caveolin-1 down-regulation abolishes estrogens-dependent survival of neurons. Thus, caveolin-1 appears to be an important player in mediating, at least, some of the non-genomic action of estrogens in neurons, in particular ERK1/2 kinetics of activation and survival.

  • Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells.
    Publication Date: 01/10/2014, on Journal of cellular physiology
    by Quintavalle C, Di Costanzo S, Zanca C, Tasset I, Fraldi A, Incoronato M, Mirabelli P, Monti M, Ballabio A, Pucci P, Cuervo AM, Condorelli G
    DOI: 10.1002/jcp.24569

    PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70 kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms.

  • The brain network for self-feeling: a symptom-lesion mapping study.
    Publication Date: 01/10/2014, on Neuropsychologia
    by Grossi D, Di Vita A, Palermo L, Sabatini U, Trojano L, Guariglia C
    DOI: 10.1016/j.neuropsychologia.2014.08.004

    Ongoing signals from one's own body (interoception) allow experience of self-feeling. In early studies interoception strictly referred to the awareness of visceral sensation but recent theories have expanded this concept to denote the ongoing status of the body. Here we asked left and right focal brain-damaged patients to answer questions about their interoceptive feelings, and correlated their responses to a quantitative measure of their lesions (voxel-based symptom-lesion mapping). By these means we could reveal that three key structures contribute to building up the feeling of self, namely insula (interoceptive modulator), amygdala (emotional modulator) and putamen (motor modulator). This brain network may be necessary for the integrity of self-feeling. A dysfunction of this network might impair perception of the inner body state, and also account for psychological disturbances, such as the somatic symptom disorders, in which individuals experience subjective symptoms suggesting physical illness or injury despite medical test results which are normal, and clinical examination do not disclose relevant medical conditions.

  • The paired box transcription factor Pax8 is essential for function and survival of adult thyroid cells.
    Publication Date: 01/10/2014, on Molecular and cellular endocrinology
    by Marotta P, Amendola E, Scarfò M, De Luca P, Zoppoli P, Amoresano A, De Felice M, Di Lauro R
    DOI: 10.1016/j.mce.2014.08.004

    The transcription factor Pax8 is already known to be essential at very early stages of mouse thyroid gland development, before the onset of thyroid hormone production. In this paper we show, using a conditional inactivation strategy, that the removal of the Pax8 protein late in gland development results in severe hypothyroidism, consequent to a reduced gland size and a deranged differentiation. These results demonstrate that Pax8 is also an essential player in controlling survival and differentiation of adult thyroid follicular cells.