1,720,957 research outputs found
Novel molecular mechanisms involved in the pathogenesis of GH-secreting pituitary adenomas
Get PDFPituitary tumors usually show a particular benign nature, with a slow growth potential. Despite these characteristics, they can cause severe complications due to their excessive hormone secretion. Still, further investigations are needed to understand the molecular mechanisms implicated in their development in detail. AHRR (Aryl Hydrocarbon Receptor (AHR) Repressor) and HSP90 (Heat Shock Protein 90) are good candidates for playing a role in pituitary tumorigenesis due to their tumorigenic role reported in different types of tumors and their action in the metabolism of endocrine disruptors (EDs), in which AIP (Aryl Hydrocarbon Receptor Interacting Protein) is also implicated. AHR Repressor (AHRR) is the main regulator of AHR activity through a negative feedback mechanism, which impairment leads to tumor-promoting events. Accordingly, AHRR downregulation was reported in several malignancies including colon, breast and lung cancer and was correlated with a more malignant phenotype (e.g. resistance to apoptosis, increased cellular motility and angiogenic potential) in different tumor cell lines. Although several studies investigated the potential role of AHR signaling in pituitary tumorigenesis, so far no data has been available on the role of AHRR in pituitary tumorigenesis. Therefore, the primary aim of the present study was to evaluate the possible role of AHRR in influencing the tumor phenotype in the somato-lactotroph cell line GH3 in which AHRR was stably silenced or overexpressed. AHRR-silenced cells showed a less aggressive phenotype due to a decreased cell viability and to a more pronounced resistance to apoptosis-inducing stimulus in comparison to the control. Correspondingly, opposite results were obtained for the stable overexpression of AHRR. In addition, AHRR silencing increased senescence-associated beta galactosidase (SA-β Gal) staining in accordance with a slow-growing phenotype observed at proliferation level, without having effect on cell cycle progression. No correlation was observed between AHRR mRNA expression in human pituitary adenomas and tumor aggressiveness, although GH-secreting tumors displayed a higher expression of AHRR in comparison to normal pituitaries.
The second part of this thesis was aimed at the role of HSP90 in the pathogenesis of GH-secreting tumors. In addition to the stabilization of AHR, this protein plays a pivotal role in maturation and stabilization of other proteins implicated in oncogenic signaling and cancer progression, and treatment with HSP90 inhibitors has recently shown promising results in pituitary corticotroph adenomas. Therefore, the function of HSP90 was investigated in GH-secreting pituitary adenomas. An intense HSP90 immunoreactivity was reported in 8 out of 25 GH-secreting pituitary tumors. In order to study the therapeutic potential of HSP90 inhibition in these tumors, the cell line GH3 was treated with different HSP90 inhibitors. The C-terminal HSP90 inhibitors novobiocin and KU174 dose-dependently decreased GH promoter activity, whereas only KU174 decreased GH secretory levels.
Conclusively, the data presented herein provide novel insights in the pathogenesis of GH-secreting pituitary adenomas. AHRR might have an oncogenic role by influencing tumor aggressiveness, as shown in the cellular model. Moreover, the results obtained in the second part suggest that HSP90 might have a role in the tumorigenesis of GH-secreting pituitary tumors and a potential for HSP90 C-terminal inhibitors in managing the excess of GH secretion
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Translational research in pituitary tumours
Get PDFAlthough effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing's disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.Fil: Stalla, Günter K. No especifíca;Fil: Dimopoulou, Christina. Technische Universitat München; AlemaniaFil: Jung Sievers, Caroline. No especifíca;Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Paez Pereda, Marcelo. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Theodoropoulou, Marily. Technische Universitat München; AlemaniaFil: Ciato, Denis. Technische Universitat München; AlemaniaFil: Renner, Ulrich. Max Planck Institut Fur Psychiatrie; Alemani
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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