1,720,966 research outputs found
Effetti del lisofosfolipide edelfosina e della tricostatina A sulla crescita di cellule di adenocarcinoma pancreatico e meccanismi molecolari associati
No full textGli alchilisofosfolipidi sono una classe di molecole di nuova generazione con forte attività
antitumorale che agisce a livello delle membrane cellulari, anziché avere come bersaglio il DNA. In
particolare, negli ultimi anni, l’attenzione si è concentrata su una in particolare di queste molecole,
l’edelfosina. E’ stato dimostrato, soprattutto in cellule leucemiche, che l’utilizzo di edelfosina è in
grado di indurre inibizione della proliferazione cellulare attraverso molteplici vie, quali, ad
esempio, l’induzione dell’apoptosi, il blocco di ciclo cellulare, il blocco delle vie di traduzione del
segnale, la produzione di specie reattive dell’ossigeno (ROS). Infatti, esperimenti in vitro hanno
messo in evidenza come l’edelfosina possa indurre aggregazione del recettore di Fas permettendo
l’avvio di una cascata del segnale che porta a morte apoptotica. Inoltre, l’edelfosina interferisce con
proteine appartenenti a determinate vie di traduzione del segnale bloccandone l’attività ed
impedendo così la proliferazione cellulare. L’utilizzo, poi, di analoghi dell’edelfosina con inibitori
delle deacetilasi istoniche ha mostrato un forte effetto sinergico sull’inibizione della proliferazione
cellulare e sull’induzione dell’apoptosi, in associazione con l’inattivazione di ERK1/2 e di Akt.
In questo lavoro abbiamo dimostrato che TSA ed edelfosina determinano inibizione della
crescita cellulare in cinque linee di adenocarcinoma pancreatico. Entrambe queste molecole, però,
non hanno mostrato effetto sulla crescita di fibroblasti primari umani. Abbiamo anche dimostrato
che TSA ed edelfosina, in trattamento combinato, determinano un forte effetto sinergico
sull’inibizione della proliferazione cellulare in tutte e cinque le linee analizzate.
L’analisi dei profili di espressione genica ha messo in evidenza che TSA è in grado di indurre
geni coivolti nella regolazione del ciclo cellulare, come p27 e p19 e che induce il gene proapoptotico
Bim, mentre reprime il gene anti-apoptotico Bcl-W. Il trattamento con edelfosina non ha
mostrato modulazioni significative dell’espressione genica, suggerendo che l’inibizione della
proliferazione cellulare provocata da edelfosina possa agire con meccanismi diversi dalla
regolazione della trascrizione genica.. Il trattamento combinato TSA/edelfosina, invece, ha messo in
evidenza la regolazione di alcuni geni che intervengono in diversi processi biologici: Neuropilina-1
e Heat Shock Protein 90 regolano la proliferazione cellulare, Tissue Factor Pathway Inhibitor-2,
Dineina, “Clusterina”, Death Inducine Protein intervengono nella regolazione dell’apoptosi,
Proteina Chinasi-Calcio/Calmodulina-dipendente nella trasduzione del segnale e Angiopoietina-4
nel rimodellamento vascolare.
Infine, esperimenti atti a chiarire quali fossero i meccanismi molecolari coinvolti
nell’inibizione della crescita hanno dimostrato che nel trattamento con TSA le cellule vanno
incontro a morte apoptotica e a blocco del ciclo cellulare in fase G2/M; nel trattamento con
edelfosina non si osserva apoptosi, ma solo un blocco di ciclo in fase G1. Il trattamento combinato
non mostra l’effetto sinergico in nessuno dei due fenomeni, suggerendo che i meccanismi coinvolti
nell’inibizione della proliferazione e nell’instaurarsi del sinergismo siano altri e dovranno essere
indagati ulteriormente.not availabl
Immunophenotypic measurable residual disease monitoring in adult acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation
Full text linkAllogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a survival benefit to adult patients affected by acute lymphoblastic leukemia (ALL). However, to avoid an overt disease relapse, patients with pre or post transplant persistence or occurrence of measurable residual disease (MRD) may require cellular or pharmacological interventions with eventual side effects. While the significance of multiparametric flow cytometry (MFC) in the guidance of ALL treatment in both adult and pediatric patients is undebated, fewer data are available regarding the impact of MRD monitoring, as assessed by MFC analysis, in the allo-HSCT settings. Aim of this article is to summarize and discuss currently available information on the role of MFC detection of MRD in adult ALL patients undergoing allo-HSCT. The significance of MFC-based MRD according to sensitivity level, timing, and in relation to molecular techniques of MRD and chimerism assessment will be also discussed
Mitochondrial sensorineural hearing loss: a retrospective study and a description of cochlear implantation in a MELAS patient.
No full textHearing impairment is common in patients with mitochondrial disorders, affecting over half of all cases at some time in the course of the disease. In some patients, deafness is only part of a multisystem disorder. By contrast, there are also a number of "pure" mitochondrial deafness disorders, the most common probably being maternally inherited. We retrospectively analyzed the last 60 genetically confirmed mitochondrial disorders diagnosed in our Department: 28 had bilateral sensorineural hearing loss, whereas 32 didn't present ear's abnormalities, without difference about sex and age of onset between each single group of diseases. We reported also a case of MELAS patient with sensorineural hearing loss, in which cochlear implantation greatly contributed to the patient's quality of life. Our study suggests that sensorineural hearing loss is an important feature in mitochondrial disorders and indicated that cochlear implantation can be recommended for patients with MELAS syndrome and others mitochondrial disorders
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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