446 research outputs found
MicroRNAs as biomarker of Parkinson disease? Small but mighty.
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Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD. [Neurology. 2015
Efficiency, products and mechanisms of ethyl acetate oxidative degradation in air non-thermal plasma
No full textEthyl acetate (EA) is a popular solvent and diluent in many products and one of the most ubiquitous organic pollutants of indoor air. Although EA's ascertained toxicity is classified as low, exposure to its vapors at concentrations 400 ppm causes serious problems in humans. EA is thus a frequent target in testing novel technologies for air purification. We report here an investigation of EA oxidative degradation in air at room temperature and atmospheric pressure induced by corona discharges. Three corona regimes, dc-, dc+ and pulsed +, were tested in the same reactor under various experimental conditions with regard to EA initial concentration (C 0) and the presence of humidity in the system. The EA degradation process was monitored by gas chromatography (GC)-flame ionization detection, GC-mass spectrometry and Fourier transform infrared spectroscopy analysis of the treated gas. These analyses yielded the concentration of residual EA (C) and those of its major products of oxidation (CO2, CO) and revealed a few organic reaction intermediates formed along the oxidation chain. The process energy efficiency was determined as energy constant, k E (kJ-1 l) and as energy yield, EY (g kW-1 h-1). The efficiency depends on the type of corona (pulsed + >dc- >dc+), on the presence of humidity in the air (improvement in the case of dc-, little or no effect for dc+) and on C 0 (k E increases linearly with 1/C 0). CO2 and CO were the major carbon containing products, confirming the strong oxidizing power of air non-thermal plasma. Acetic acid and acetaldehyde were detected in very small amounts as reaction intermediates. The experimental results obtained in this work support the conclusion that different reactive species are involved in the initial step of EA oxidation in the case of dc- and dc+ corona air non-thermal plasma
MicroRNA Expression Profiling and Its Clinical Impact in Breast Cancer
No full textBreast cancer is the leading cause of cancer death in women worldwide.
Gene expression studies have been used over the last decades to defi ne the signature of different breast cancer subtypes and to predict outcome and response to therapies.
Recently, microRNAs (miRNAs) have been linked to several human diseases, including cancer. An aberrant miRNA expression in breast cancer was fi rst reported in 2005. Now, an increasing body of experimental evidences supports the role of these small molecules in the tumorigenic process and their potential use as cancer specifi c biomarkers. Indeed, miRNAs are detectable as circulating molecules in the blood. In this chapter, we summarize our knowledge about the involvement of miRNAs in breast cancer and their potential as diagnostic, prognostic and therapeutic tools
MicroRNA coinvolti nello sviluppo del carcinoma epatocellulare. Identificazione delle proteine bersaglio.
No full textIl complesso mosaico dei meccanismi che regolano l’espressione genica si è recentemente arricchito di un nuovo tassello grazie alla scoperta dei microRNA (miRNA). Questo gruppo di piccoli RNA con funzione regolatoria ha catalizzato su di sé l’interesse del mondo scientifico da quando si è visto che questi RNA, della lunghezza di circa 22 nucleotidi, non solo sono altamente conservati tra le diverse specie, segno di una loro origine ancestrale, ma sono anche in grado di influenzare i livelli di espressione di numerose e specifiche proteine che ne costituiscono il bersaglio.
La scoperta dei microRNA avvenne all’inizio degli anni ’90 grazie a studi svolti in C. elegans. In questo nematode, fu scoperto che un piccolo RNA, lin-4, era responsabile dello spegnimento di una proteina che regola lo sviluppo larvale. Gli studi successivi, che si estesero anche ad altri organismi, permisero di capire che i microRNA costituiscono una grande famiglia di molecole in grado di regolare l’espressione genica a livello post-trascrizionale. Il loro ruolo appare molto diffuso e circa il 50% dei geni umani codificanti per proteine potrebbe essere in parte regolato da microRNA. Infatti, ciascun miRNA è in grado di esercitare la sua azione contemporaneamente su molti bersagli tramite l’appaiamento di sequenza con regioni omologhe nel 3’UTR del mRNA: dopo i diversi passaggi maturativi da pri-miRNA a pre-miRNA, il miRNA maturo (miR), lungo 22-25 nucleotidi, si appaia, per omologia di sequenza, con il 3’UTR dei geni bersaglio inducendo o il taglio proteolitico del mRNA o il blocco della traduzione proteica (questo secondo meccanismo è quello più frequente nelle cellule animali). È perciò logico che i microRNA abbiano come bersaglio geni coinvolti in tutte le funzioni cellulari e non solo nello sviluppo.
Pur essendo ancora numerosi gli aspetti da chiarire, a partire per esempio dal numero esatto di miRNA nei diversi organismi, emerge chiaramente l’importanza del ruolo di questi piccoli RNA nella fisiologia cellulare. È pertanto plausibile che alterazioni dei miRNA siano coinvolte in patologie umane. Infatti, accanto a ricerche volte a delucidare i meccanismi d’azione dei microRNA, si sono sviluppati diversi filoni di ricerca aventi lo scopo ultimo di rispondere a questa domanda: se i microRNA hanno un ruolo fisiologico così importante per la cellula, che cosa succede se la loro espressione viene alterata? O ancora, esistono patologie la cui causa sia attribuibile ad alterazioni dell’espressione dei microRNA o nella cui patogenesi siano coinvolte anche alterazioni dei microRNA? Il mio progetto si sviluppa in questo ambito. In particolare, la mia attenzione si rivolgerà allo studio delle eventuali alterazioni dell’espressione dei microRNA in tumori umani e alla messa a punto di sistemi utili per la correzione di queste alterazioni. Vi sono già evidenze che i microRNA siano espressi in modo aberrante in tumori umani. La prima evidenza è venuta dallo studio di caratterizzazione della delezione al cromosoma 13q14 nella leucemia linfatica cronica (LLC), in cui solo i mir-15a e mir-16-1 furono ritrovati nella minima regione di delezione [1]. Successivamente, mir-143 e mir-145 sono stati trovati significativamente sotto-espressi in carcinomi del colon [2], mentre il mir-155 è stato trovato sovra-espresso in linfomi di Burkitt ed altri tipi di linfoma [3, 4]. Infine, la scoperta che let-7, significativamente sottoespresso in tumori del polmone [5], ha come bersagli gli oncogeni K-RAS, N-RAS e H-RAS [6] ha dato supporto all’idea che i microRNA possano agire come oncogeni o come oncosoppressori, suggerendo anche che un’espressione aberrante dei microRNA in cellule tumorali possa identificare microRNA coinvolti nella patogenesi tumorale.
OBIETTIVI E STRATEGIE DI INDAGINE
Partendo da queste considerazioni preliminari, il mio progetto di studio si pone i seguenti obiettivi specifici:
1. Identificare i microRNA differenzialmente espressi in neoplasie umane, in particolare in epatocarcinomi confrontati con la loro controparte normale e con tessuti cirrotici.
2. Identificare il profilo di espressione dei microRNA associati a specifiche caratteristiche clinico-patologiche.
3. Identificare i geni bersaglio dei microRNA la cui espressione sia risultata alterata in HCC.
4. Sviluppare saggi funzionali in vitro ed in vivo con linee cellulari tumorali umane per valutare l’effetto biologico e molecolare dei microRNA la cui espressione sia risultata alterata nelle neoplasie e la validazione dei geni bersaglio tramite saggio dell'attività luciferasica e westrn blot
MicroRNAs in human cancer: from research to therapy
No full textNumerous miRNAs are deregulated in human cancers, and experimental evidence indicates that they can play roles as oncogenes or tumor suppressor genes. Similarly to cancer genes that encode proteins, deregulation of miRNA-encoding genes is associated with genetic or epigenetic alterations, such as deletions, amplifications, point mutations and aberrant DNA methylation. The discovery that miRNAs interact with known oncogenes has established further links with molecular pathways implicated in malignant transformation. Finally, miRNAs can be used as diagnostic markers, and their potential as therapeutic molecules has moved miRNAs from the area of basic research to the field of cancer biotechnology
Experimental current-voltage characteristics of Bi2223/Ag tapes and BSCCO current leads
No full textThe paper presents and analyses several tests aimed at representing the electrical characteristics of a sample of commercial Bi2223/Ag tapes (length: ∼ 1.1m) and of a cave cylindrical sample of pure BSCCO, in zero applied magnetic field. A typical hysteresis phenomenon has been observed at temperature below 120 K
Clinical histopathological features and CDKN2A/CDK4/MITF mutational status of patients with multiple primary melanomas from Bologna: Italy is a fascinating but complex mosaic
No full textBACKGROUND: The incidence of cutaneous melanoma (cm) has increased in the last decades. germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2a) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer. METHODS: We retrospectively analyzed the data of patients with prior diagnosis of cm referring to our service from January 2005 to may 2017. the aim was to investigate the rate of multiple cms (mPm), assessing their clinical/pathological features. moreover, the genetic tests of patients who had undergone CDKN2A/CDKN2B, CDK4 and MITF screening were evaluated. RESULTS: One hundred fifteen patients (9.26%) were diagnosed with MPMs: 70 males (60.87%) and 45 women (39.13%). 75 patients (43 males and 32 females) underwent genetic screening for germline mutations. The screening revealed that 4/75 patients (5.33%) were carriers of the non-synonymous missense variation c.442g>a (p.ala148thr) in CDKN2A exon 2 in heterozygosis, 3 of whom had at least one in-situ melanoma. In 1 patient (1.33%) we detected the variation c.249C>A, p.His83Gln in CDKN2A exon 2 in heterozygosis and in 1 patient (1.33%) the mutation c.952g>a (p.glu318lys) in MITF gene was found. CONCLUSIONS: This study confirms the need for a full body skin examination and a prolonged surveillance in patients affected by cM, as MPMs were detected in up to 10% of total cases in our series and synchronous lesions in 1/5. Moreover, it reflects the great variability of cM high-susceptibility genes mutational status within the Italian territory. Patients carrying c.952g>a (p.glu318lys) MITF mutation have a higher risk to develop a nodular cm
A transcriptome-wide approach reveals the key contribution of NFI-A in promoting erythroid differentiation of human CD34(+) progenitors and CML cells
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Cancer of unknown primary: Challenges and progress in clinical management
No full textPatients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. Advancements have been made in the molecular characterization of this tumor, which could be used to infer the tumor site-of-origin and thus broaden the diagnostic outcome. Moreover, we describe here the novel therapeutic opportunities that are based on the genetic and immunophenotypic characterization of the tumor, and thus independent from the tumor type, which could provide most benefit to patients with cancer of unknown primary. Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3-5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies
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