1,721,012 research outputs found
Alterata espressione dei geni coinvolti nel processo di sumoilazione nel carcinoma papillare della tiroide.
No full textLa modificazione post-traslazionale di proteine da parte delle proteine SUMO (small ubiquitin-related modifiers) consiste nella loro coniugazione covalente e reversibile a specifici residui di lisina di proteine bersaglio, con conseguente alterazione della localizzazione subcellulare e dell’attività di queste ultime. La SUMOilazione è implicata in svariati processi biologici tra cui la proliferazione cellulare, l’apoptosi, la riparazione del DNA e la sopravvivenza cellulare. Studi recenti hanno mostrato che la deregolazione del sistema SUMO contribuisce alla trasformazione tumorale modificando l’attività di molteplici oncoproteine e oncosoppressori. Ad oggi, si conosce molto poco riguardo al ruolo della SUMOilazione nel carcinoma papillare della tiroide (PTC). Pertanto, la presente ricerca è stata volta a caratterizzare l’espressione a livello di mRNA di un pannello di geni coinvolti nel processo di SUMOilazione in questo tumore. In particolare, è stata analizzata l’espressione dei geni: a) codificanti per gli enzimi SENP, cistein-proteasi in grado di rimuovere le proteine SUMO dalle proteine bersaglio; b) codificanti per SAE1 e UBA2 che formano un eterodimero attivante le proteine SUMO; c) codificante l’enzima coniugante Ubc9; d) codificanti le E3 ligasi PIAS1-4, RanBP2, NSMCE2, CBX4 e ZMIZ1-2. A tal fine, 20 campioni di tessuto normale e tumorale prelevati da pazienti affetti da PTC sono stati sottoposti a RT-PCR quantitativa, e l’analisi dei dati è stata eseguita con il software Lightcycler Relative Quantification. I risultati ottenuti hanno evidenziato una diminuzione significativa dei livelli di mRNA dei geni SAE1, ZMIZ1, PIAS1, PIAS2 e SENP8. Benché la rilevanza di tali alterazioni nel contesto degli eventi di SUMOilazione debba essere ancora determinata, le nostre osservazioni evidenziano una deregolazione del processo di SUMOilazione nei PTC, che merita ulteriori approfondimenti al fine di accertarne l’eventuale ruolo patogenetico
Ability of selective small molecule inhibitors of Aurora-A and Aurora-B in inhibiting tumorigenicity of anaplastic thyroid carcinoma-derived cell lines.
No full textAurora kinases are a family of serine/threonine kinases which play an essential role in cell division. Their aberrant expression and/or function bring about severe mitotic abnormalities resulting in either cell death or aneuploidy. Aurora kinases are often found overexpressed in a variety of malignancies among which thyroid cancers, and particularly in the most aggressive form, the anaplastic thyroid carcinoma (ATC). In previous studies we demonstrated the in vitro efficacy of small molecule inhibitors of Aurora kinases in restraining cell growth and survival of different ATC derived cell lines. In the present preclinical study we sought to establish which of the Auroras is the best drug target for ATC therapy. To this end, the effects of two selective inhibitors of Aurora-A (MLN8237/Alisertib) and Aurora-B (AZD1152/Barasertib) have been analyzed on a panel of human ATC derived cell lines (CAL-62, BHT-101, 8305C, 8505C). Both inhibitors reduced proliferation of the different cancer cells in a time- and dose-dependent manner, with IC50 ranges of 17.5-86 nM for MLN8237 and of 59-380 nM for AZD1152. Western blot experiments demonstrated that concentrations of inhibitors exerting maximal anti-proliferative effects were still selective for Aurora-A or -B. Moreover, as evidenced by immunofluorescence and time-lapse experiments, each inhibitor induced a distinct cellular phenotype depending on the kinase targeted. Polyploidy increased significantly in all the cell lines treated with AZD1152 and in 2 out of 4 lines treated with MLN8237, while apoptosis was induced by both treatments in all cells. Both drugs were also capable to block anchorage-independent ATC cell growth.
In conclusion, our results indicate that selective inhibitors of Aurora-A or Aurora-B display similar efficacy in inhibiting tumorigenicity of ATC-derived cell lines and they might represent new therapeutic options for ATC treatment
New molecular approaches in the diagnosis and prognosis of thyroid cancer patients
Get PDFThyroid nodules are very common in the adult population, but only a minority of them harbor a malignant lesion. Therefore, the first aim in their clinical evaluation is to exclude malignancy. To date, the fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules and cervical lymph nodes (CLN) suspected of metastatic disease. It has to be mentioned, however, that FNAC on thyroid nodules suffers from a major diagnostic limit represented by cellular atypias of indeterminate significance, which require the histological diagnosis. Also the FNAC performed on CLN may be a challenging diagnostic category as CLN could harbor metastases from a multiplicity of extrathyroidal malignancies or be affected by several non-tumoral diseases. In addition, inadequate cellularity obtained from both thyroid nodules or CLN prevents diagnosis in about 20% of specimens. Total thyroidectomy followed by adjuvant therapy with 131I is the treatment of choice for most patients affected by DTC. Although the prognosis of DTC patients is favorable, about 20% of them face the morbidity of disease recurrence and tumor-related deaths. Thus far, the prognosis of these patients still relies on clinic-pathological variables such as patient’s age, tumor size, histology, lymph node or distant metastasis, which are not accurate in predicting the long-term outcome. As a consequence, the identification of new molecular biomarkers strictly related to the risk of DTC relapse is highly needed. In the present review we’ll attempt to summarize the recent characterization of new molecular markers able to ameliorate the diagnosis and prognosis of thyroid cancer patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
