1,720,954 research outputs found
Leukaemia inhibitory factor protects cholangiocarcinoma cells from drug-induced apoptosis via a STAT3-independent, PI3K-dependent, Mcl-1 activation
No full textBackground and Aim. Cholangiocarcinoma (CCA) is an aggressive, chemoresistant liver malignancy characterised by an abundant desmoplasia. Tumour-stromal interactions promote cancer development and thus could be targets of interventional therapies. Leukaemia inhibitory factor (LIF), an IL-6 family cytokine, promotes development and progression of various epithelial cancers, however very little is known about its effects in CCA. We aimed to investigate a possible role of LIF and its receptor (LIFR) in the pathogenesis of CCA.
Methods. LIF, LIFR and gp130 distributions were evaluated by immunohistochemistry in archived human histological samples derived from surgical resection (n=19). LIF secretion (ELISA) and LIFR expression (Western blotting) were assessed in freshly isolated human primary cholangiocytes (n=8) and established CCA cell lines (n=3). Using the two established CCA cell lines that expressed LIFR, we tested LIF’s effects on: proliferation, viability (both MTS) and apoptosis (caspase 3 and 7 activation) with/without chemotherapeutic agents (cisplatin, gemcitabine, paclitaxel or camptothecin), migration (scratch assay), invasion (Boyden chambers), stem cell-like phenotype (Nanog and Oct4 gene expression by real-time PCR), and expression levels of pro-apoptotic (pBax) and anti-apoptotic (Mcl-1 with/without PI3K inhibition) proteins, and pSTAT3 (Western blotting).
Results. LIF and LIFR were more extensive in neoplastic than control bile ducts; LIF was also widespread amongst tumour stromal cells. LIF had minimal effects on cell proliferation, migration, invasion, and induction of a stem cell-like phenotype, whilst it significantly counteracted drug-induced apoptosis. Upon LIF stimulation, decreased caspase 3/7 activation was associated with increased Mcl-1 expression attenuated by PI3K inhibition whereas pBax and pSTAT3 remained unchanged.
Conclusions. Autocrine and paracrine LIF signalling may promote chemoresistance in CCA by up-regulating Mcl-1. This pro-survival capability may be mediated by a novel STAT3-independent, PI3K-dependent pathway.Razionale e scopo. Il colangiocarcinoma (CCA) è una neoplasia epatica estremamente aggressiva e chemioresistente, caratterizzata da un’abbondante desmoplasia. Le interazioni stroma-tumore possono promuovere lo sviluppo tumorale e per questo possono risultare dei buoni bersagli per una terapia potenzialmente curativa. Il leukaemia inhibitory factor (LIF), è una citochina appartenente alla famiglia dell’IL-6 ed è in grado di promuovere lo sviluppo e la progressione di un ampio numero di tumori epiteliali, ma poco si sa della sua funzione e dei suoi effetti nel CCA. Il nostro scopo è quello di studiare il ruolo di LIF e del suo recettore (LIFR) nella patogenesi del CCA.
Metodi. La distribuzione di LIF, LIFR e gp130 è stata valutata tramite immunoistochimica su tessuti umani di archivio derivanti da resezioni chirurgiche per CCA (n=19). La secrezione di LIF (ELISA) e l’espressione di LIFR (Western blotting) sono state valutate su colture primarie di colangiociti umani ottenuti da resezioni per CCA (n=8) e su linee stabili di CCA (n=3). Abbiamo quindi testato su due linee stabilizzate di CCA esprimenti LIFR: la proliferazione, la vitalità (entrambi con MTS) e l’apoptosi cellulare (attivazione delle caspasi 3/7) con/senza trattamento con agenti chemioterapici (cis-platino, gemcitabina, paclitaxel o camptotecina), la migrazione (scratch assay), l’invasione (camere di Boyden), l’induzione di un fenotipo simil-staminale (espressione genica di Nanog e Oct4 con real-time PCR) ed infine i livelli di espressione di proteine pro- (pBax) ed anti-apoptotiche (Mcl-1 con/senza inibizione di PI3K) e di pSTAT3 (Western blot).
Risultati. LIF e LIFR risultano maggiormente espressi nelle strutture neoplastiche che nei dotti biliari peritumorali; LIF risulta inoltre espressa da gran parte delle cellule dello stroma tumorale. Gli effetti del LIF su proliferazione, migrazione, invasione e induzione di un fenotipo simil-staminale sono minimi, di contro esso protegge le cellule tumorali dall’apoptosi indotta da farmaci. Dopo la stimolazione con LIF, si osserva una riduzione dell’attivazione delle caspasi 3/7 associata ad un aumento dell’espressione di Mcl-1, la quale viene diminuita dall’inibizione della PI3K; l’espressione di pBax e pSTAT3 non risultano invece modulate.
Conclusioni. Il segnale di LIF può promuovere, sia per via autocrina che paracrina, la chemioresistenza del CCA aumentando i livelli di espressione di Mcl-1. Queste capacità favorenti la sopravvivenza cellulare sono mediate da una nuova via di segnale STAT3-indipendente e PI3K-dipendente
Protein kinase A-dependent pSer(675) -beta-catenin, a novel signaling defect in a mouse model of congenital hepatic fibrosis
No full textThese data show that in fibrocystin-defective cholangiocytes, cAMP/PKA signaling stimulates pSer(675) -phosphorylation of ?-catenin and Rac-1 activity. In the presence of activated Rac-1, pSer(675) -?-catenin is translocated to the nucleus, becomes transcriptionally active, and is responsible for increased motility of Pkhd1(del4/del4) cholangiocytes. ?-Catenin-dependent changes in cell motility may be central to the pathogenesis of the disease and represent a potential therapeutic targe
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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