1,720,961 research outputs found
Cellular proteome alterations in response to hypoxia inducible factor HIF-2α in normoxic neuroblastoma cells
No full textIl neuroblastoma (NB) è un tumore embrionale del sistema nervoso simpatico, che deriva da cellule della cresta neurale. È il tumore extracranico più diffuso tra i bambini di età inferiore a un anno e rappresenta circa il 7% di tutti i tumori infantili. L'ipossia si sviluppa comunemente durante la crescita tumorale ed è associata ad una prognosi infausta con resistenza ai trattamenti terapeutici. Molte evidenze suggeriscono una correlazione tra i fattori ipossia-inducibile (HIF), HIF-1α e HIF-2α, con il grado di differenziamento e quindi l’aggressività tumorale. In particolare, nel Neuroblastoma HIF-2α è stabile anche in condizioni di normossiche e continua ad essere attivo anche dopo 48-72 ore dall’ipossia. In NB HIF-2α, localizzato principalmente nelle nicchie peri-vascolare del tumore ed è correlato ad una prognosi infausta. Studi recenti hanno dimostrato il coinvolgimento di HIF-2α nella proliferazione e nell’aumento della aggressività tumorale. Lo scopo del progetto è quello di acquisire ulteriori informazioni sui meccanismi molecolari indotti dall’over-espressione di HIF-2α che sono alla base della resistenza ai convenzionali trattamenti terapeutici. Il nostro progetto, quindi, propone un approccio proteomico, basato sull’analisi DIGE e sull’identificazione di antigeni di membrana (FACS), per identificare nuovi bersagli prognostici e terapeutici per il trattamento clinico di forme di NB più aggressive e resistenti ai protocolli terapeutici convenzionali. Attraverso l’indagine DIGE e studi funzionali sono stati identificati nel nostro sistema sperimentale diverse proteine coinvolte nel metabolismo cellulare e nei processi di regolazione dell’mRNA. Inoltre sono stati identificati nuovi antigeni di membrana differenzialmente espressi soffermandoci sulle proprietà antiadesive e proinvasive di CD55, marker specifico di HIF-2α.Quindi, CD55 potrebbe essere usato nella diagnosi e per la stratificazione di pazienti affetti da forme più aggressive di Neuroblastoma.Neuroblastoma (NB) is an embryonal tumor of neuroectodermal cells derived from precursor or immature cells of the sympathetic nervous system (SNS). This disease rappresents the most common extracranial tumor in infants, accounting for 8% to 10% of all childhood cancer and for approximately 15% of cancer deaths in children. The deep knowledge of NB biology is imperative toward the development of novel therapy. Hypoxia is a typical feature of several solid tumors microenvironment and is associated with a poor prognosis and resistance to therapy. The relationship among hypoxia, tumor phenotypes and clinical parameters in NB is not well characterized. Tumor adaptation to hypoxia is mainly mediated by two transcription factors: the hypoxia-inducible factors (HIFs) HIF-1α and HIF-2α. HIF-2α is stable also in normoxia condition and continues to be active even after 48–72 h of hypoxia in some neuroblastoma cell lines thus indicate that HIF-2α plays a critical role in driving the hypoxic response. Interesting, HIF-2α is correlated with poor patient prognosis in NB and is localizated in tumor peri-vascular niches. These findings indicate that HIF-2α protein expression in NB samples at normoxic levels might affect the aggressive tumor phenotype. The main aim of my phD program has been to get new insights into the molecular mechanism of tumor aggressiveness mediated by HIF-2α protein overexpression in NB cells. Interesting, HIF-2α overexpressing cells acquire an undifferentiated phenotype and the ability to grow as neurospheres in soft agar. Then I applied two different proteomic approaches, DIGE analysis and FACS detection of membrane antigens to identify new putative prognostic and therapeutic hypoxia-related targets to be used in clinical treatment of aggressive NB forms. The identified proteins have important roles in a variety of pathways such as “citrate cycle”, “glycolysis” and “splicesoma” thus indicating that HIF-2α over-expression affects the cellular metabolic balance and increases the processes of mRNA regulation. These findings might provide an innovative therapeutic strategy by combining anti-metabolic drugs and pathways inhibitors.Among the cell surface antigens which were differentialy HIF-2α regulated CD55 was the most significantly expressed marker in our cellular system. I assessed CD55 has anti-adhesive and pro-invading functions that might provide the basis for NB solid tumors to survive as microscopic residual disease. Furthermore, the use of CD55 antibody-based visualization as in PET (Positron Emission Tomography) imaging will have implications for the development of more accurate diagnosis and prognosis in challenging cases and for driving personalized treatment. In conclusion, the HIF-2α novel markers identified in this study might improve patients risk stratification and could be also used as putative drug targets being immunotherapy is one of the most promising anticancer treatment
Inhibition of hypoxia inducible factors combined with all-trans retinoic acid treatment enhances glial transdifferentiation of neuroblastoma cells
No full textNeuroblastoma (NBL) is a heterogeneous tumor characterized by a wide range of clinical manifestations. A high tumor cell differentiation grade correlates to a favorable stage and positive outcome. Expression of the hypoxia inducible factors HIF1-α (HIF1A gene) and HIF2-α (EPAS1 gene) and/or hypoxia-regulated pathways has been shown to promote the undifferentiated phenotype of NBL cells. Our hypothesis is that HIF1A and EPAS1 expression represent one of the mechanisms responsible for the lack of responsiveness of NBL to differentiation therapy. Clinically, high levels of HIF1A and EPAS1 expression were associated with inferior survival in two NBL microarray datasets, and patient subgroups with lower expression of HIF1A and EPAS1 showed significant enrichment of pathways related to neuronal differentiation. In NBL cell lines, the combination of all-trans retinoic acid (ATRA) with HIF1A or EPAS1 silencing led to an acquired glial-cell phenotype and enhanced expression of glial-cell differentiation markers. Furthermore, HIF1A or EPAS1 silencing might promote cell senescence independent of ATRA treatment. Taken together, our data suggest that HIF inhibition coupled with ATRA treatment promotes differentiation into a more benign phenotype and cell senescence in vitro. These findings open the way for additional lines of attack in the treatment of NBL minimal residue disease
Erratum to: Association Study between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population (Journal of Cardiovascular Translational Research, (2017), 10, 5-6, (455-458), 10.1007/s12265-017-9758-9)
No full textThe author affiliation for both Guido Iaccarino and Michele Ciccarelli is Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno. The currently mentioned affiliations (Department of Advanced Biomedical SciencesFederico II University NaplesItaly and IRCCS SDN Istituto di Ricerca Diagnostica e Nucleare Naples Italy respectively) are not correct
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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