1,720,958 research outputs found
OXIDATIVE STRESS INDUCES CROSS-REGULATION BETWEEN EGFR AND BER PATHWAYS IN HUMAN THYROCYTES
No full textIntroduction.
The main clinical concern about thyroid nodules (TNs) is their possible hidden malignancy. To date mechanisms involved in TNs malignant transition are unresolved. In thyroid H2O2 is produced in large quantities and may play a role in the pathogenesis of TNs. Increased levels of 8-oxo-guanidine DNA adducts were recently detected in TNs and contribute to mutagenesis, which, in turn may result in cell proliferation and survival. DNA base lesions, generated by an excess of reactive oxygen species, are physiologically removed by Base Excision Repair (BER) pathway. A link between Epidermal Growth Factor Receptor (EGFR) signaling and DNA repair mechanisms has been documented, however, their cross-regulation is poorly understood in thyroid tissue pathophysiology. This study investigated the mechanisms involved in cross-regulation between EGFR and BER molecular pathways in normal human thyrocytes after H2O2 exposure and EGF treatment. Materials and Methods. Normal human thyroid epithelial cells, Nthy-ori3-1, were treated with H2O2, alone or combined with EGF and inhibitors PD98059, and LY294002 to specifically block the MAPK (Erk) kinases and PI3-kinase pathways. EGFR and BER pathways expression and activation were tested by Western Blot and quantitative gene expression (qRT-PCR).
Results. In response to H2O2, alone or combined with EGF, we observed a time-dependent increase of OGG1 and MUTYH gene expression that was reversed by EGF treatment and by LY alone or combined with H2O2. EGF alone induces EGFR over-expression as well as LY, alone and H2O2 combined. Noteworthy H2O2, alone and combined with EGF, induced a fast kinetic of ErbB2 gene expression. In contrast LY, alone and combined with H2O2, reduced its expression. These results indicated that ErbB2 is modulated in response to oxidative stress through an Akt-dependent mechanism. Surprisingly, PD enhanced the ErbB2 expression compared with untreated and H2O2-treated cells. Therefore, H2O2 treatment, alone or combined with EGF, LY, and PD resulted in EGFR activation at tyrosine residue 1068. Similar results were obtained analyzing MAPK phosphorylation except after co-treatment with EGF and H2O2. Finally, the analysis of PARP1 expression level showed a moderate reduction after treatments with H2O2 combined with EGF and inhibitors. Conclusion. Our observations present the first evidence that a pronounced stress with H2O2 may induce a cross-regulation between EGF and BER pathways in thyroid epithelial cells
Is right colectomy a complete learning procedure for a robotic surgical program?
No full textThis study analyses the utility of right colectomy as a learning procedure at the beginning of a robotic surgical program. The hypothesis is that right colectomy contains all the technical steps necessary to acquire basic abilities in robotics surgery. The first 23 consecutive robotic right colectomy performed at the beginning of a robotic program were analysed. All surgical times were recorded in the operating room and second checked on a dedicated video-database. Specific robotic times were analysed using CUSUM method to evaluate the learning curve. CUSUM-derived learning phases were compared. Fourteen males and nine females with a mean age of 68.7 (46-84) underwent robotic right colectomy. The mean overall time was 265.3 min (180-320 min), docking time was 7 min (5-12 min), console time was 205.9 min (145-260 min), and anastomotic time was 43.6 (25-60 min). CUSUM analyses identified two learning phases: "starting phase" and "consolidation phase". Interphase comparison confirmed the significant (p < 0.05) differences between the two phases. Robotic technology facilitates the training process in minimally invasive colorectal surgery. At the beginning of the learning curve, right colectomy could represent a complete procedure to be proficient in robotic colorectal surgery
The first evidence that oxidative stress induces EGFR and BER pathways cross-regulation in human thyrocytes.
No full textINTRODUCTION. The main clinical concern about thyroid nodules is their possible hidden malignancy. One of the most interesting aspects of thyroid cells is their physiological production of H2O2 for hormone synthesis, but it can increase DNA lesions, which are repaired by BER. A link between EGFR and BER has been documented, but, their cross-regulation is unclear. This study investigated the effect of oxidative stress on ERBB and BER signalling in a normal thyroid cell model. MATERIALS AND METHODS. Nthy-ori3-1 cells (Nthy), were treated with H2O2, EGF, LY294002 (LY) and PD98059 (PD) alone and combined. Goiter tissues were obtained from patients undergoing thyroidectomy. ERBB and BER were analysed by Western Blot and qRT-PCR; gene expression data were evaluated by bioinformatics tools. RESULTS. BER genes showed the same trend for each treatment in Nthy cells. In particular, MUTYH gene expression clustered with other BER genes under oxidative stress conditions, whereas EGF co-treatment induced its significant correlation with PPARγ and ERBB2, which was lost after LY and PD treatment. Gene cluster analysis suggested a pivotal role for JUN/AP1 transcription factor. In goiters tissues with clinical inflammatory features, gene expression showed MUTYH and OGG1 correlation. While JUN/AP1 gene showed a positive correlation with ERBB2 in not-inflammatory goiters. Finally, OGG1 protein expression, in Nthy cells, decreased under H2O2 treatment, contrary to EGFR phosphorylation/activation, except for co-treatment with EGF. CONCLUSIONS. Our observations present the first experimental evidence that oxidative stress may induce a cross-regulation between EGFR and BER pathways in thyroid cells
ErbB receptors and BER pathways in human gastric tumours: molecular implication of oxidative stres.
No full textBackground: Deregulation and cross-talk of intracellular signals have been shown to be the driving forces in cancers. In this study, ErbB and
BER pathways in neoplastic gastric tissues and cells, as a molecular signature for tumor progression, were investigated.
Methods: ErbBs and BER molecular signaling genes and proteins were evaluated in the gastric carcinoma cell line AGS in basal condition and after single or combined treatments with H2O2, EGF and LY294002 and in primary gastric carcinoma tissues by RT-qPCR and Western blot.
Results: Increased levels of pEGFR and pMAPK were detected in AGS cells after treatments with H2O2, although EGFR expression did not show any significant change. In addition, H2O2 treatment downregulated pAKT, as compared to control or EGF-treated cells. PARP-1 expression was decreased after H2O2 treatment, while OGG1 protein and gene expression decreased with LY294002 treatment, suggesting an Akt-dependent mechanism. An upregulation of ErbB2 gene expression was observed after EGF treatment, while ErbB4 expression increased with H2O2 and LY294002. Nrf2 and APE1 gene expression levels were reduced by H2O2 and LY294002 combined treatments. Data on gastric tissues showed that EGFR, highly expressed in intestinal-type, diffuse-type gastric carcinomas and their normal counterparts, was not phosphorylated in all cases. In contrast, diffuse-type carcinomas showed increased pMAPK, pAKT and OGG1 expression, as compared to control tissues. ErbB2 and Mutyh gene expression levels were higher in intestinal-type than in diffuse-type carcinomas, while ErbB4 showed an opposite expression pattern.
Conclusions: These data indicate that oxidative stress modify EGFR and BER signaling, suggesting an integrated role between these pathways
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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