1,720,976 research outputs found
Exploring whether Traditional Lecture or Problem Based Learning approaches improve knowledge gain and student perceptions within neuroanatomy near-peer teaching
No full textUsing multimedia approaches to strengthen the application of radiology to anatomy teaching in a clinical neuroanatomy module
No full textThe radiological paradigm shift: using cross-sectional imaging to improve the understanding of anatomy in the gastrointestinal module
No full textLeukaemia 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
Evaluation of a new automated spotter style exam for assessment of anatomical knowledge
No full textThe use of traditional specimen-based anatomy spotters as a means of assessment has declined in recent years. This is partly due to increasing student numbers and thus time required for conducting such exams; marker variability and impartiality are also issues. In an attempt to address these problems, we introduced a robust and modified MCQ-style spotter exam for dental students. Predominantly image based, the examination requires students to choose from multiple answer options. Either a positive whole mark per question is awarded or fraction thereof according to the following algorithm: x = a/max(b,c), where x = score per question, a = number of matched correct answers, b = actual number of correct answers, and c = total number of answers selected by candidate. Performance in conventional specimen-based spotter assessments was compared with that of the MCQ-style format, and minimal differences between average marks were noted. Advantages of the MCQ format include automated marking and thus consistent accurate scores, reduced marking time, and consistency between different administrators. Disadvantages include initial time for preparation and checking of master answer sheet, clear instructions for students who require a formative assessment. In conclusion, this MCQ-style examination may provide significant advantages for institutions unable to conduct traditional spotter exams
Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies
No full textCholangiocarcinoma (CCA) is a very aggressive neoplasm, whose incidence has steadily increased in the last decade. Despite its growing epidemiological impact, therapeutic chances with a curative intent are still limited to surgical resection and, in highly selected cases, to liver transplantation. Unfortunately, in most cases at the time of diagnosis, CCA has already metastasized to regional lymph nodes, thereby reducing the opportunities for curative treatment. Mechanisms governing CCA invasiveness are unclear. A critical element of CCA is the abundant “tumor reactive stroma”, which develops in close association with tumor growth. An abundant reactive stroma is present in a number of carcinomas characterized by strong invasiveness, namely gastric, colorectal and pancreatic cancers, as well as breast cancer. In tumor stroma, a variety of signals and mediators are reciprocally exchanged between stromal and cancer cells that, in turn acquire pro-invasive properties. These paracrine communications have started to be elucidated only recently, and may represent targets amenable of specific therapeutic intervention. In this review, we will highlight the cell types that compose the tumor reactive stroma in CCA and some of the molecular interactions possibly responsible for increased invasiveness of CCA. The possibility of dissecting, and likely exploiting, these interactions for potential new treatments will be also describe
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
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