1,720,990 research outputs found
Effects of osilodrostat and metyrapone on 2D and 3D models of adrenocortical carcinoma cell lines viability: preliminary results
Full text linkAdrenocortical carcinoma (ACC) is a rare but aggressive malignancy, with a poor overall survival. It can present itself in different ways, but most of the patients display symptoms of hormonal excess. Mitotane is a treatment option as an adjuvant therapy after surgery or for unresectable/advanced ACC, also combined in a platinum-based therapy. It is an adrenolytic drug that affects adrenal steroidogenesis and interferes with mitochondrial function reducing cell viability. Other therapeutics are used to relieve the symptoms of ACC with hypercortisolism, such as metyrapone and osilodrostat, both steroidogenesis inhibitors. Specifically, osilodrostat is a drug that inhibits adrenal 11β-hydroxylase and blocks aldosterone synthase, which are enzymes acting in the final step of cortisol and aldosterone synthesis. The main objective of this research consists of the comparison of effects of mitotane, metyrapone and osilodrostat on adrenocortical carcinoma cell lines, such as SW-13 and NCI-H295R: the first is a non-secreting cell line, the second is a glucocorticoids-, mineralocorticoids-, and adrenal androgen-secreting line, often used as a model in experiments on human steroidogenesis. While the effects of metyrapone and osilodrostat on ACC hypercortisolism have been proven in the last few years, there is no specific data about their effects on tumoral cells viability and how they can influence them. In this view, a study involving both cell lines could be an effective method to assess valuable information from an in vitro model. Both for SW-13 and NCI-H295R cells, the experiments were performed with 2D cultures and then 3D models (e.g. spheroids) to reproduce the complex structure of an in vivo environment. The cultures were treated with different concentrations of mitotane, metyrapone and osilodrostat. Moreover, a combination of mitotane and osilodrostat and of mitotane and metyrapone were tested on ACC cell cultures. 2D models were cultured in DMEM-F12 medium supplemented with 10% of fetal bovine serum (SW13 cells) or with DMEM-F12 medium supplemented with 2.5% of Nu-Serum and ITS+ Premix supplement (NCI-H295R). Cell viability was assessed with MTS assay. 3D models were obtained using specific microwell plates to be evaluated via a physical cytometer establishing information about spheroids features and indirectly to cell death extent. Although the study is currently in a preliminary phase, we evaluated changes in cell viability and in steroidogenesis in 2D models. The next step will consist of a deeper characterization and evaluation of 3D models
Survivin (BIRC5): Implications in cancer therapy
Full text linkInhibitors of Apoptosis proteins (IAPs) were discovered through experiments aimed at rescuing apoptosis in insects. Classically associated with the inhibition of apoptosis, the IAP member Survivin also regulates cell cycle progression and is an essential component of the Chromosomal Passenger Complex (CPC), responsible for chromosomal segregation. Although undetectable in most adult tissues, Survivin is expressed in Adult Stem Cells (ASCs) and plays a crucial role in their maintenance. Survivin is overexpressed in most cancers, contributing to their clonal expansion. As a result, it has been proposed as a possible anticancer target for nearly two decades. In this discussion, we will explore the rationale behind Survivin as a therapeutic target, focusing on common cancer types such as carcinomas, sarcomas, and leukemias. We will delve into the modulation of Survivin by cancer pro-survival cell signaling, the association between SNPs and tumorigenesis, and its regulation by miRNAs. Finally, we will compare cell growth, clonogenic capacity, and apoptosis, along with different strategies for Survivin inhibition, including gene expression and protein activity modulation
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
The promising approach of 3D bioprinting for diabetic foot ulcer treatment: A concise review of recent developments
Full text linkDiabetic foot ulcer (DFU), one of the most significant complications of diabetes, is a condition that causes anatomical and functional alterations of the foot resulting in an important social and economic impact, related to disability and health care costs. Recently, three-dimensional bioprinting - which allows the fabrication of complex and biocompatible structures - has been identified as a promising approach in the field of regenerative medicine to promote the healing of chronic wounds, such as DFU. In this concise review we highlight the most relevant and recent attempts of using 3D bioprinted constructs in vivo - both on animals and people - in order to treat non-healing diabetic ulcers and prevent their worsening. Finally, we briefly focus on the future implications of bioprinting, suggesting its forthcoming importance not only for DFU treatment but also for other areas of clinical care
Irisin: A Possible Marker of Adipose Tissue Dysfunction in Obesity
Full text linkAdipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-α (TNFα) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNFα-induced ECM remodeling and a possible implication of irisin in AT impairment in obesity. ASCs and AMCs were exposed to TNFα treatment and nuclear factor–kappa (NF-kB) pathway was investigated: Tissue Inhibitor of Metalloproteinase (TIMP-1), Twist Family Transcription Factor 1 (TWIST-1), and peroxisome proliferator-activated receptor-γ (PPARγ) expression levels were analyzed. The proteolytic activity of matrix metalloproteinases (MMPs) -2 and -9 was analyzed by zymography, and the irisin protein content was measured by ELISA. In inflamed AMCs, a TIMP-1/TWIST-1 imbalance leads to a drop in PPARγ. Adipogenesis and lipid storage ability impairment come with local tissue remodeling due to MMP-9 overactivation. In vitro and ex vivo measurements confirm positive correlations among inflammation, adipose secreting irisin levels, and circulating irisin levels in patients with visceral obesity. Our findings identify the NF-kB downstream effectors as molecular initiators of AT dysfunction and suggest irisin as a possible AT damage and obesity predictive factor
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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