1,720,994 research outputs found
THE COMPLEX RELATIONSHIP BETWEEN CHRONIC INFLAMMATION AND DIFFERENTIATED THYROID CANCER: EVIDENCE FROM IN VITRO AND CLINICAL STUDIES
Full text linkInflammation is an essential component of malignancies, including differentiated thyroid cancer (DTC). Thyroid cancer microenvironment is composed of a mixture of immune cells and soluble mediators. Among them, the chemokine CXCL8 exerts multiple pro-tumorigenic activities, including a chemotactic action on circulating neutrophils, induction of tumor cells growth, increase in angiogenesis and induction of the epithelial to mesenchymal transition, which promotes cell migration. Clinical studies in patients affected by several types of cancer evidenced that CXCL8 serum levels reflect the tumor burden and are related with the tumor aggressiveness. Solid evidence indicates that CXCL8 targeting can reduce tumor progression. The controversial relationship between inflammation and thyroid cancer tumorigenesis involves also the debated topic of the association between chronic-autoimmune-thyroiditis (CAT) and (DTC). DTCs are often diagnosed in the context of CAT and display an inflammatory-immune cells infiltration at histology, but whether the malignant transformation is promoted by the inflammatory response, or the peri-tumoral inflammation is induced by cancer-specific inflammatory molecules is still a matter of debate. This thesis project had two principal aims, i) to investigate the role of a pro-tumorigenic chemokine (CXCL8) in thyroid cancer microenvironment and to test in vitro the modulating properties of two different pharmacologic agents (PLX4720 and phenformin) and ii) to evaluate if CAT is a risk factor for the de novo development of DTC through a longitudinal population study. For Aim 1, thyroid cancer cell lines both BRAFV600E mutated (BCPAP, 8305C, 8505C) and RET/PTC rearranged (TPC-1), and normal human thyrocytes (NHT) were cultured alone or after treatment with two PLX4720 ore phenformin at increasing concentrations. CXCL8 concentrations were measured in the cell supernatants. Cell viability was evaluated through WST-1 and Annexin/propidium assay. Metastatic potential was assessed with migration assay and colony formation assay. For Aim 2, a retrospective longitudinal cohort study was designed including 510 CAT patients with a 10-years follow-up. The results of the first part of the thesis demonstrate that thyroid cancer cells secrete high amounts of CXCL8 and that both PLX4720 and phenformin are able to exert several anti-cancer activities within cancer microenvironment that are in part due to the inhibition of CXCL8 secretion. The results of the second part of the study indicate that the presence of CAT is not a risk factor for the new onset of DTC during long-term follow-up. The results of this thesis project suggest that two different kinds of inflammation (cancer-related and autoimmunity-related) exert different effects on DTC microenvironment and could have opposite effects on DTC development and prognosis
The multifaceted anti-cancer effects of BRAF-inhibitors
No full textThe BRAF gene is commonly involved in normal processes of cell growth and differentiation. The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade. In particular, BRAFV600E mutation is found in those melanoma or thyroid cancer refractory to the common therapy and with a more aggressive phenotype. BRAF V600E was found to influence the composition of the so-called tumour microenvironment modulating both solid (immune-cell infiltration) and soluble (chemokines) mediators, which balance characterize the ultimate behaviour of the tumour, making it more or less aggressive. In particular, the presence of BRAFV600E mutation would be associated with a change of this balance to a more aggressive phenotype of the tumour and a worse prognosis. The investigation of the possible modulation of those components of tumour microenvironment is nowadays object of several studies as a new potential target therapy in those more complicated cases. At present several clinical trials both in melanoma and thyroid cancer are using BRAF-inhibitors with encouraging results, which are derived also from numerous in vitro pre-clinical studies aimed at evaluate the possible modulation of immune-cell density and of specific pro-tumorigenic chemokine secretion (CXCL8 and CCL2) by several BRAF-inhibitors in the context of melanoma and thyroid cancer. This review will encompass in vitro and in vivo studies which investigated the modulation of the tumour microenvironment by BRAF-inhibitors, highlighting also the most recent clinical trials with a specific focus on melanoma and thyroid cancer
Per-polyfluoroalkyl substances (PFAS) as thyroid disruptors: is there evidence for multi-transgenerational effects?
No full textIntroductionThe environmental spread of pollutants has led to a persistent exposure of living beings to multiple chemicals, by now become ubiquitous in the surrounding environment. Environmental exposure to these substances has been reported to cause multi- and/or transgenerational health effects. Per- and Polyfluorinated Substances (PFAS) raise great concern, given their known effects both as endocrine disruptors and potential carcinogens. The multi/trans-generational effects of different endocrine disruptors have been investigated by several studies, and harmful effects observed also for PFAS.Areas coveredThis review examines the current data on the multi-trans-generational effects of PFAS, with a focus on their impact on the thyroid axis. The aim is to determine if there is evidence of potential multi-trans-generational effects of PFAS on the thyroid and/or if more research is needed.Expert opinionPFAS exposure impacts thyroid homeostasis and can cross the placental barrier. In addition PFAS have shown multi-transgenerational effects in laboratory experiences and animal models, but thyroid disruptive effects of PFAS were also investigated only in a small number of these studies. Efforts are needed to study the adverse effects of PFAS, as not all PFAS are regulated and removal strategies are still being developed
The interplay between subclinical hypothyroidism and poor sleep quality: A systematic review
No full textBackground: The relationship between subclinical hypothyroidism (SHYPO) and sleep disturbances is still poorly investigated. This systematic review aims to critically appraise the existing literature to provide more insights in understanding whether SHYPO favors sleep disturbances or it is the sleep disturbance per se that affects the hypothalamus-pituitary-thyroid axis regulation. Methods: Original studies on sleep quality and duration in patients with SHYPO were searched in the PubMed/ MEDLINE, Embase, Web of Science and Scopus databases. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of included studies. Results: Eight studies, including 2916 patients with SHYPO and 18,574 healthy controls, were retrieved. An overall agreement (7 out of 8 studies), about a positive correlation between decreased sleep quality and/or duration and SHYPO was observed. Five studies investigated sleep quality through self-reported surveys; only two studies explored both subjective and objective assessment of sleep quality with actigraphy (n n = 1) or polysomnography (n n = 1); finally, one study assessed subjective evaluation of sleep quality through a single question regarding the number of sleeping hours. A high level of heterogeneity among studies was manifest due to differences in population source, sleep measure assessment and criteria for diagnosing SHYPO. Discussion: Overall, the existing literature data suggest a link between SHYPO and sleep disturbances, but further studies on larger populations of patients with homogeneous study designs and outcomes are warranted
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
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