361 research outputs found

    New insights on the role of epigenetic alterations in hepatocellular carcinoma

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    Maddalena Frau,1 Claudio F Feo,2 Francesco Feo,1 Rosa M Pascale11Department of Clinical and Experimental Medicine, Division of Experimental Pathology and Oncology, 2Department of Clinical and Experimental Medicine, Division of Surgery. University of Sassari, Sassari, ItalyAbstract: Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in methionine metabolism, promoter hypermethylation, or increased proteasomal degradation of oncosuppressors, as well as posttranscriptional deregulation by microRNA or messenger RNA (mRNA) binding proteins. Alterations in the methylation of the promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in decreased S-adenosylmethionine level, global DNA hypomethylation, and deregulation of signal transduction pathways linked to methionine metabolism and methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may also depend on MAT1A mRNA destabilization associated with MAT2A mRNA stabilization by specific proteins. Decrease in MAT1A expression has also been attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs targeting oncosuppressor genes and down-regulation of miRNAs targeting genes involved in cell-cycle and signal transduction control. Oncosuppressor gene down-regulation in HCC is also induced by promoter hypermethylation or posttranslational deregulation, leading to proteasomal degradation. The role of epigenetic changes in hepatocarcinogenesis has recently suggested new promising therapeutic approaches for HCC on the basis of the administration of methylating agents, inhibition of methyl adenosyltransferases, and restoration of the expression of tumor-suppressor miRNAs.Keywords: hepatocarcinogenesis, DNA methylation, microRNA, Piwi-interacting RNAs, stem cells, therapeutic target

    The Orbit accumulation on the CF depends on KLP3A, Feo and Polo.

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    <p>Time-lapse observation of Orbit in spermatocytes expressing dsRNA for 6 cytokinesis-related genes. Filled arrowheads show the focus of myosin, while the open arrowheads indicate the absence of the focus. (A)Normal control. (B)Depletion of <i>KLP3A</i>. Orbit foci on the CF were not detected (0 cells with detectable Orbit foci on the CF/18 total cells examined). (C) Depletion of <i>feo</i>. The Orbit foci were not observed (0/11). (D) Depletion of <i>polo</i>. The Orbit foci were not observed (0/5). (E) Depletion of <i>pav</i>. The Orbit foci appeared on the CF (10/12). (F) Depletion of <i>pebble</i>. The foci were observed on the CF (5/5). Time of onset of CF ingression was set at t = 0 min. Scale bars  = 10 µm.</p

    Analysis of lunar pyroclastic deposit FeO abundances by LRO Diviner

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    [1] Thermal infrared reflectance spectra of rock‐forming minerals include a prominent minimum near 8μm, known as the “Christiansen feature” (CF). The inflection point wavelength is sensitive to the degree of polymerization of silicates, which is strongly influenced by major cations – notably iron – in the minerals. Laboratory spectra of lunar soils demonstrate that the CF location is closely correlated to the sample's bulk FeO abundance, across the full range of Apollo soil samples, including pyroclastic glass. This correlation is the basis for estimating lunar surface FeO abundances using orbital thermal infrared measurements. The Diviner Lunar Radiometer Experiment on the Lunar Reconnaissance Orbiter includes three thermal infrared channels, selected to determine the CF positions for sites across the lunar surface. Diviner measurements are used to derive FeO abundances in the Aristarchus, Sulpicius Gallus, and Rima Fresnel pyroclastic deposits. The calculated FeO abundances for Aristarchus and Sulpicius Gallus lie within the compositional range of FeO‐rich pyroclastic glasses but outside the range of most mare soils, supporting the interpretations of these deposits as glass rich. The calculated FeO abundance for the Rima Fresnel deposit is close to that of mare soils, supporting a contention that this deposit is dominated by basaltic fragments rather than glass. The Diviner measurements hold the potential to determine FeO abundances in many lunar pyroclastic deposits. A better understanding of these compositions will provide insight into the magmatic history and composition of the lunar interior, as well as an enhanced inventory of potential resources for future human exploration

    IDATIDOSI EPATICA. TRATTAMENTO CONVENZIONALE E NUOVE METODICHE: NOSTRA ESPERIENZA.

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    Introduzione: Il trattamento dell’idatidosi epatica ha subito nel corso degli ultimi anni un profondo mutamento derivato principalmente dall’affermarsi di tecniche alternative alla chirurgia tradizionale, quali la chirurgia video-laparoscopica e il trattamento percutaneo eco-guidato. Il trattamento chirurgico tradizionale viene a tutt’oggi considerato il gold standard, mentre le indicazioni e i limiti delle altre metodiche rimangono ancora oggetto di discussione. Metodo: Abbiamo eseguito una revisione critica dei casi di idatidosi epatica trattati presso il nostro Istituto dal 1981 al giugno 2004, analizzando i risultati e i vantaggi delle diverse forme di trattamento utilizzate. Su un totale di 275 pazienti, 232 sono stati sottoposti a trattamento chirurgico tradizionale, 5 a trattamento video-laparoscopico e 38 alla metodica PAIR (puntura, aspirazione, iniezione, riaspirazione) eco-guidata. Il trattamento chirurgico tradizionale è consistito nella maggior parte dei casi in una pericistectomia radicale e in alcuni casi, all’inizio del periodo considerato, in una marsupializzazione. La PAIR è stata eseguita per cisti di tipo I e III; 25 pazienti presentavano cisti multiple, in 8 casi la lesione parassitaria era recidiva ad un pregresso intervento eseguito in altra sede. Il trattamento video-laparoscopico è stato riservato a cisti a sviluppo esofitico ed è consistito nella pericistectomia radicale “a cisti chiusa” in 4 casi e in una pericistectomia “a cisti semi-chiusa” preceduta da PAIR in uno. Risultati: Nel gruppo di pazienti sottoposti ad intervento tradizionale abbiamo osservato una mortalità dello 0,8%, una morbilità del 3% e nessun caso di recidiva. Nei pazienti sottoposti a PAIR è stata riscontrata una percentuale di recidive del 5,3% (tutte trattate con terapia medica, tranne in un caso in cui è stata ripetuta la procedura dopo otto mesi) e una percentuale di complicanze (tutte di lieve entità) del 7,9%. Nei 5 casi di tecnica vido-laparoscopica non si sono rilevate complicanze e non si sono verificate recidive. Conclusioni: L’analisi dei risultati rivela come la chirurgia tradizionale sia in grado di ottenere, rispetto alla PAIR, una maggiore sicurezza nel prevenire le recidive e come sia da considerare senza dubbio la metodica di scelta nelle cisti complicate. La tecnica per-cutanea si va affermando come una metodica efficace che in molti casi, per pazienti ad alto rischio operatorio o con particolare localizzazione delle cisti, si propone come alternativa a quella chirurgica. Il trattamento video-laparoscopico rimane appannaggio di pochi casi attentamente selezionati
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