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https://www.readbyqxmd.com/read/29662630/type-ii-raf-inhibitor-causes-superior-erk-pathway-suppression-compared-to-type-i-raf-inhibitor-in-cells-expressing-different-braf-mutant-types-recurrently-found-in-lung-cancer
#1
Amir Noeparast, Philippe Giron, Sylvia De Brakeleer, Carolien Eggermont, Ulrike De Ridder, Erik Teugels, Jacques De Grève
A large fraction of somatic driver BRAF mutations in lung cancer are non-V600 and impaired-kinase. Non-V600 BRAF mutations predict sensitivity to combination of a type I RAF inhibitor, Dabrafenib, and a MEK inhibitor, Trametinib. Singly, Dabrafenib only weakly suppresses mutant BRAF-induced ERK signaling and can induce ERK paradoxical activation in CRAF-overexpressing cells. The present study compared the effects of Dabrafenib and a type II RAF inhibitor, AZ628, on ERK activity in HEK293T cells expressing several tumor-derived BRAF mutants, and in a non-V600 and impaired-kinase BRAF-mutant lung cancer cell line (H1666)...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29660597/risk-stratification-of-sentinel-node-positive-melanoma-patients-defines-surgical-management-and-adjuvant-therapy-treatment-considerations
#2
Daniëlle Verver, David van Klaveren, Alexander C J van Akkooi, Piotr Rutkowski, Barry W E M Powell, Caroline Robert, Alessandro Testori, Barbara L van Leeuwen, Astrid A M van der Veldt, Ulrich Keilholz, Alexander M M Eggermont, Cornelis Verhoef, Dirk J Grünhagen
BACKGROUND: In light of the evolving landscape of adjuvant therapy in melanoma and the recently confirmed absent survival benefit of completion lymph node dissection (CLND), it becomes important to explore possible consequences of omitting CLND, and whether it is possible to adequately stratify positive sentinel node (SN) patients solely based on information retrieved from the melanoma up to the sentinel lymph node biopsy (SLNB). METHODS: A retrospective cohort from nine European Organization for Research and Treatment of Cancer Melanoma Group centres was used...
April 13, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29658430/adjuvant-pembrolizumab-versus-placebo-in-resected-stage-iii-melanoma
#3
Alexander M M Eggermont, Christian U Blank, Mario Mandala, Georgina V Long, Victoria Atkinson, Stéphane Dalle, Andrew Haydon, Mikhail Lichinitser, Adnan Khattak, Matteo S Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A Ascierto, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Michele Maio, Alfonsus J M van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Paul Lorigan, Nageatte Ibrahim, Sandrine Marreaud, Alexander C J van Akkooi, Stefan Suciu, Caroline Robert
Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred...
April 15, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29607800/feasibility-and-impact-study-of-a-reward-based-mobile-application-to-improve-adolescents-snacking-habits
#4
Nathalie De Cock, Wendy Van Lippevelde, Jolien Vangeel, Melissa Notebaert, Kathleen Beullens, Steven Eggermont, Benedicte Deforche, Lea Maes, Lien Goossens, Sandra Verbeken, Ellen Moens, Leentje Vervoort, Caroline Braet, Lieven Huybregts, Patrick Kolsteren, John Van Camp, Carl Lachat
OBJECTIVE: Adolescents' snacking habits are driven by both explicit reflective and implicit hedonic processes. Hedonic pathways and differences in sensitivity to food rewards in addition to reflective determinants should be considered. The present study evaluated the feasibility and impact of a mobile phone-delivered intervention, incorporating explicit reflective and implicit rewarding strategies, on adolescents' snack intake. DESIGN: Adolescents (n 988; mean age 14·9 (sd 0·70) years, 59·4 % boys) completed a non-randomized clustered controlled trial...
April 2, 2018: Public Health Nutrition
https://www.readbyqxmd.com/read/29572779/how-social-and-mass-media-relate-to-youth-s-self-sexualization-taking-a-cross-national-perspective-on-rewarded-appearance-ideals
#5
Jolien Trekels, Kathrin Karsay, Steven Eggermont, Laura Vandenbosch
Although media exposure has been related to cognitive preoccupation with appearance, research rarely investigated adolescents' behavioral self-sexualization. To address this gap, the present study among 12- to 16-year-olds (N = 1527; 50.2% girls) in Austria, Belgium, Spain, and South-Korea (1) investigates whether different types of media use relate to self-sexualization, (2) explores the explanatory value of rewarded appearance ideals, and (3) considers culture and gender as moderating factors. Despite cultural variation, a general trend of increasing self-sexualization with social media use and magazine reading appeared across the countries...
March 23, 2018: Journal of Youth and Adolescence
https://www.readbyqxmd.com/read/29555205/store-independent-coupling-between-the-secretory-pathway-ca-2-transport-atpase-spca1-and-orai1-in-golgi-stress-and-hailey-hailey-disease
#6
Susanne Smaardijk, Jialin Chen, Sara Kerselaers, Thomas Voets, Jan Eggermont, Peter Vangheluwe
The Secretory Pathway Ca2+ ATPases SPCA1 and SPCA2 transport Ca2+ and Mn2+ into the Golgi and Secretory Pathway. SPCA2 mediates store-independent Ca2+ entry (SICE) via STIM1-independent activation of Orai1, inducing constitutive Ca2+ influx in mammary epithelial cells during lactation. Here, we show that like SPCA2, also the overexpression of the ubiquitous SPCA1 induces cytosolic Ca2+ influx, which is abolished by Orai1 knockdown and occurs independently of STIM1. This process elevates the Ca2+ concentration in the cytosol and in the non-endoplasmic reticulum (ER) stores, pointing to a functional coupling between Orai1 and SPCA1...
March 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29508905/effect-of-different-ct-scanners-and-settings-on-femoral-failure-loads-calculated-by-finite-element-models
#7
Florieke Eggermont, Loes Derikx, Jeffrey Free, Ruud van Leeuwen, Yvette van der Linden, Nico Verdonschot, Esther Tanck
In a multi-center patient study, using different CT scanners, CT-based finite element (FE) models are utilized to calculate failure loads of femora with metastases. Previous studies showed that using different CT scanners can result in different outcomes. This study aims to quantify the effects of 1) different CT scanners, 2) different CT protocols with variations in slice thickness, field of view (FOV) and reconstruction kernel, and 3) air between calibration phantom and patient, on Hounsfield Units (HU), bone mineral density (BMD) and FE failure load...
March 6, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29505581/parkinson-disease-related-atp13a2-evolved-early-in-animal-evolution
#8
Danny Mollerup Sørensen, Tine Holemans, Sarah van Veen, Shaun Martin, Tugce Arslan, Ida Winther Haagendahl, Henrik Waldal Holen, Norin Nabil Hamouda, Jan Eggermont, Michael Palmgren, Peter Vangheluwe
Several human P5-type transport ATPases are implicated in neurological disorders, but little is known about their physiological function and properties. Here, we investigated the relationship between the five mammalian P5 isoforms ATP13A1-5 in a comparative study. We demonstrated that ATP13A1-4 isoforms undergo autophosphorylation, which is a hallmark P-type ATPase property that is required for substrate transport. A phylogenetic analysis of P5 sequences revealed that ATP13A1 represents clade P5A, which is highly conserved between fungi and animals with one member in each investigated species...
2018: PloS One
https://www.readbyqxmd.com/read/29488886/quality-difference-of-neointima-following-the-implantation-of-bioresorbable-scaffold-and-metallic-stent-in-patients-with-st-elevation-myocardial-infarction-quantitative-assessments-by-light-intensity-light-attenuation-and-backscatter-on-optical-coherence-tomography
#9
Yohei Sotomi, Yoshinobu Onuma, Shengnan Liu, Taku Asano, Jeroen Eggermont, Yuki Katagiri, Rafael Cavalcante, Robbert J de Winter, Joanna J Wykrzykowska, Salvatore Brugaletta, Lorenz Räber, Manel Sabaté, Stephan Windecker, Jouke Dijkstra, Patrick W Serruys
AIMS: We aimed to assess possible difference of the neointimal quality after everolimus-eluting bioresorbable scaffold (BVS) implantation in comparison with cobalt chromium everolimus-eluting scaffold (CoCr-EES) by optical frequency domain imaging (OFDI). METHODS AND RESULTS: This study is a post-hoc analysis of TROFI II trial assessing neointimal quality 6-month after the implantation of BVS(N=82) and CoCr-EES(N=87) in STEMI patients. Neointimal light property analysis by OFDI full-automatically computed light attenuation, backscatter and light intensity for superficial and deep neointima...
February 27, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29451373/regional-structural-and-functional-specialisations-in-the-urethra-of-the-female-rat-evidence-for-complex-physiological-control-systems
#10
Monica Eggermont, Stefan De Wachter, Jane Eastham, James Gillespie
The present study characterises the complex structural and functional elements of the female rat urethra that may be involved in controlling urethral closure and continence. Urethras were dissected from female Sprague-Dawley rats (n=12) euthanized by pentobarbital overdose. Tissues were fixed (4% paraformaldehyde), frozen and sectioned (8μm) for light microscopy and immunohistochemistry. Antibodies were used to detect immunoreactivity to calcitonin gene related peptide, nitric oxide synthase, vesicular acetylcholine transporter and tyrosine hydroxylase...
February 16, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29432281/lymph-node-ratio-as-a-prognostic-factor-in-melanoma-results-from-european-organization-for-research-and-treatment-of-cancer-18871-18952-and-18991-studies
#11
Alessandro A Testori, Stefan Suciu, Alexander C J van Akkooi, Mariano Suppa, Alexander M M Eggermont, Esther de Vries, Arjen Joosse
The aim of this study was to assess the prognostic importance of lymph node ratio (LNR) in stage III melanoma after complete lymph nodal dissections. From European Organization for Research and Treatment of Cancer randomized trials 18871, 18952, and 18991, 2358 patients had full information on positive and examined lymph nodes (LNs) and were included. Cox proportional hazards models stratified by trial were used to assess the prognostic impact of LNR adjusted for confounders on melanoma-specific survival. Optimal cutoff values for LNR were calculated for each LN dissection site (axillary, inguinal, and neck)...
February 9, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29361473/neoadjuvant-therapy-in-melanoma-the-next-step
#12
Paolo A Ascierto, Alexander M M Eggermont
No abstract text is available yet for this article.
February 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29337119/sox10-single-transcription-factor-based-fast-and-efficient-generation-of-oligodendrocytes-from-human-pluripotent-stem-cells
#13
Juan Antonio García-León, Manoj Kumar, Ruben Boon, David Chau, Jennifer One, Esther Wolfs, Kristel Eggermont, Pieter Berckmans, Nilhan Gunhanlar, Femke de Vrij, Bas Lendemeijer, Benjamin Pavie, Nikky Corthout, Steven A Kushner, José Carlos Dávila, Ivo Lambrichts, Wei-Shou Hu, Catherine M Verfaillie
Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+ ) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29312568/transcriptional-response-to-hypoxic-stress-in-melanoma-and-prognostic-potential-of-gbe1-and-bnip3
#14
Stéphanie Buart, Stéphane Terry, Muhammad Z Noman, Emilie Lanoy, Céline Boutros, Paul Fogel, Philippe Dessen, Guillaume Meurice, Yann Gaston-Mathé, Philippe Vielh, Séverine Roy, Emilie Routier, Virginie Marty, Sophie Ferlicot, Luc Legrès, Morad El Bouchtaoui, Nyam Kamsu-Kom, Jane Muret, Eric Deutsch, Alexander Eggermont, Jean-Charles Soria, Caroline Robert, Salem Chouaib
Gradients of hypoxia occur in most solid tumors and cells found in hypoxic regions are associated with the most aggressive and therapy-resistant fractions of the tumor. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia in melanoma. Using microarray technology, whole genome gene expression profiling was first performed on established melanoma cell lines. From gene set enrichment analyses, we derived a robust 35 probes signature (hypomel for HYPOxia MELanoma) associated with hypoxia-response pathways, including 26 genes up regulated, and 9 genes down regulated...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29171676/tween-television-and-peers-reinforcing-social-agents-in-early-adolescents-body-surveillance-and-self-objectification
#15
Ann Rousseau, Steven Eggermont
Sociocultural models of body image posit that the media and peers play a role in early adolescents' body dissatisfaction. Introducing a sociocultural perspective on youth sexualization, the present three-wave panel study (N = 968, Mage  = 11.30) sought to examine the role of tween television and peer appearance conversations in early adolescents' body surveillance and self-objectification over time. Special attention was given to the mediating role of media internalization in these relationships. The results showed evidence for a reciprocal interaction between media internalization and peer appearance conversations and identified this reciprocal interaction as the underlying mechanism linking tween television exposure to higher levels of body surveillance and self-objectification 1 year later...
November 24, 2017: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/29152869/linking-magazine-exposure-to-social-appearance-anxiety-the-role-of-appearance-norms-in-early-adolescence
#16
Jolien Trekels, Steven Eggermont
Early adolescents (N = 1,591; Mage  = 11.698; SD = 0.892) participated in a two-wave panel study (6-month interval) to examine the longitudinal association between appearance-focused magazine exposure and social appearance anxiety. We revealed that magazine exposure positively correlated with the internalization of appearance ideals and the attribution of social rewards to attractiveness which, in turn, related to social appearance anxiety. Internalization and attribution of social rewards formed a reinforcing spiral; once internalized, early adolescents associate positive things with appearance ideals (e...
December 2017: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/29100546/the-need-for-a-network-to-establish-and-validate-predictive-biomarkers-in-cancer-immunotherapy
#17
EDITORIAL
Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and social need...
November 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29097494/gut-microbiome-influences-efficacy-of-pd-1-based-immunotherapy-against-epithelial-tumors
#18
Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie P M Duong, Maryam Tidjani Alou, Romain Daillère, Aurélie Fluckiger, Meriem Messaoudene, Conrad Rauber, Maria P Roberti, Marine Fidelle, Caroline Flament, Vichnou Poirier-Colame, Paule Opolon, Christophe Klein, Kristina Iribarren, Laura Mondragón, Nicolas Jacquelot, Bo Qu, Gladys Ferrere, Céline Clémenson, Laura Mezquita, Jordi Remon Masip, Charles Naltet, Solenn Brosseau, Coureche Kaderbhai, Corentin Richard, Hira Rizvi, Florence Levenez, Nathalie Galleron, Benoit Quinquis, Nicolas Pons, Bernhard Ryffel, Véronique Minard-Colin, Patrick Gonin, Jean-Charles Soria, Eric Deutsch, Yohann Loriot, François Ghiringhelli, Gérard Zalcman, François Goldwasser, Bernard Escudier, Matthew D Hellmann, Alexander Eggermont, Didier Raoult, Laurence Albiges, Guido Kroemer, Laurence Zitvogel
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29095202/simultaneous-inhibition-of-tumor-necrosis-factor-receptor-1-and-matrix-metalloproteinase-8-completely-protects-against-acute-inflammation-and-sepsis
#19
Sophie Steeland, Sara Van Ryckeghem, Jolien Vandewalle, Marlies Ballegeer, Elien Van Wonterghem, Melanie Eggermont, Johan Decruyenaere, Liesbet De Bus, Claude Libert, Roosmarijn E Vandenbroucke
OBJECTIVES: Sepsis causes very high mortality and morbidity rates and remains one of the biggest medical challenges. This study investigates whether plasma levels of both matrix metalloproteinase 8 and tumor necrosis factor receptor 1 are associated with sepsis severity and also investigates the therapeutic applicability of simultaneous inhibition of the two molecules in sepsis. DESIGN: Observational human pilot study-prospective controlled animal study. SETTING: University hospital and research laboratory...
January 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29095056/-i-can-should-look-like-a-media-figure-the-association-between-direct-and-indirect-media-exposure-and-teens-sexualizing-appearance-behaviors
#20
Jolien Trekels, Steven Eggermont
Prior research has examined the influence of media exposure on adolescents' sexualized self-concept, but engagement in sexualizing appearance behaviors remains understudied, especially among a younger age group (i.e., early adolescents). This three-wave panel study among 971 nine- to 14-year-olds (Mage = 12.99, SD = 1.03) showed that discussing media content with friends (i.e., indirect media exposure) was indirectly related to sexualizing appearance behaviors through perceived attainability of the appearance ideal...
November 2, 2017: Journal of Sex Research
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