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https://www.readbyqxmd.com/read/28624801/bromodomain-inhibition-shows-antitumoral-activity-in-mice-and-human-luminal-breast-cancer
#1
Montserrat Pérez-Salvia, Laia Simó-Riudalbas, Pere Llinàs-Arias, Laura Roa, Fernando Setien, Marta Soler, Manuel Castro de Moura, James E Bradner, Eva Gonzalez-Suarez, Catia Moutinho, Manel Esteller
BET bromodomain inhibitors, which have an antitumoral effect against various solid cancer tumor types, have not been studied in detail in luminal breast cancer, despite the prevalence of this subtype of mammary malignancy. Here we demonstrate that the BET bromodomain inhibitor JQ1 exerts growth-inhibitory activity in human luminal breast cancer cell lines associated with a depletion of the C-MYC oncogene, but does not alter the expression levels of the BRD4 bromodomain protein. Interestingly, expression microarray analyses indicate that, upon JQ1 administration, the antitumoral phenotype also involves downregulation of relevant breast cancer oncogenes such as the Breast Carcinoma-Amplified Sequence 1 (BCAS1) and the PDZ Domain-Containing 1 (PDZK1)...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#2
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28619845/the-prohibitin-binding-compound-fluorizoline-induces-apoptosis-in-chronic-lymphocytic-leukemia-cells-through-the-upregulation-of-noxa-and-synergizes-with-ibrutinib-aicar-or-venetoclax
#3
Ana M Cosialls, Helena Pomares, Daniel Iglesias-Serret, José Saura-Esteller, Sonia Núñez-Vázquez, Diana M González-Gironès, Esmeralda de la Banda, Sara Preciado, Fernando Albericio, Rodolfo Lavilla, Gabriel Pons, Eva M González-Barca, Joan Gil
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28603881/early-palliative-care-for-adults-with-advanced-cancer
#4
REVIEW
Markus W Haun, Stephanie Estel, Gerta Rücker, Hans-Christoph Friederich, Matthias Villalobos, Michael Thomas, Mechthild Hartmann
BACKGROUND: Incurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and psychosocial well-being. In standard cancer care, palliative measures generally are initiated when it is evident that disease-modifying treatments have been unsuccessful, no treatments can be offered, or death is anticipated. In contrast, early palliative care is initiated much earlier in the disease trajectory and closer to the diagnosis of incurable cancer...
June 12, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28581523/a-dna-methylation-map-of-human-cancer-at-single-base-pair-resolution
#5
E Vidal, S Sayols, S Moran, A Guillaumet-Adkins, M P Schroeder, R Royo, M Orozco, M Gut, I Gut, N Lopez-Bigas, H Heyn, M Esteller
Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28578692/comprehensive-dna-methylation-study-identifies-novel-progression-related-and-prognostic-markers-for-cutaneous-melanoma
#6
Jasper Wouters, Miguel Vizoso, Anna Martinez-Cardus, F Javier Carmona, Olivier Govaere, Teresa Laguna, Jesuchristopher Joseph, Peter Dynoodt, Claudia Aura, Mona Foth, Roy Cloots, Karin van den Hurk, Balazs Balint, Ian G Murphy, Enda W McDermott, Kieran Sheahan, Karin Jirström, Bjorn Nodin, Girish Mallya-Udupi, Joost J van den Oord, William M Gallagher, Manel Esteller
BACKGROUND: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses...
June 5, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28541128/epigenetic-drugs-more-than-meets-the-eye
#7
Manel Esteller
No abstract text is available yet for this article.
May 4, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28535802/n-blr-a-primate-specific-non-coding-transcript-leads-to-colorectal-cancer-invasion-and-migration
#8
Isidore Rigoutsos, Sang Kil Lee, Su Youn Nam, Simone Anfossi, Barbara Pasculli, Martin Pichler, Yi Jing, Cristian Rodriguez-Aguayo, Aristeidis G Telonis, Simona Rossi, Cristina Ivan, Tina Catela Ivkovic, Linda Fabris, Peter M Clark, Hui Ling, Masayoshi Shimizu, Roxana S Redis, Maitri Y Shah, Xinna Zhang, Yoshinaga Okugawa, Eun Jung Jung, Aristotelis Tsirigos, Li Huang, Jana Ferdin, Roberta Gafà, Riccardo Spizzo, Milena S Nicoloso, Anurag N Paranjape, Maryam Shariati, Aida Tiron, Jen Jen Yeh, Raul Teruel-Montoya, Lianchun Xiao, Sonia A Melo, David Menter, Zhi-Qin Jiang, Elsa R Flores, Massimo Negrini, Ajay Goel, Menashe Bar-Eli, Sendurai A Mani, Chang Gong Liu, Gabriel Lopez-Berestein, Ioana Berindan-Neagoe, Manel Esteller, Scott Kopetz, Giovanni Lanza, George A Calin
BACKGROUND: Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. RESULTS: We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival...
May 24, 2017: Genome Biology
https://www.readbyqxmd.com/read/28523560/stem-cell-technology-for-epi-genetic-brain-disorders
#9
Renzo J M Riemens, Edilene S Soares, Manel Esteller, Raul Delgado-Morales
Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28517110/outcome-after-medical-and-surgical-intervention-in-horses-with-temporohyoid-osteoarthropathy
#10
P M Espinosa, J E Nieto, K E Estell, P H Kass, M Aleman
BACKGROUND: Temporohyoid osteoarthropathy (THO) is a cause of neurological disease in horses characterised by facial and vestibulocochlear nerve deficits. Studies reporting and comparing survival following medical or surgical treatment of THO are lacking. OBJECTIVES: To compare survival and prognosis of horses with THO treated medically or surgically; and to report surgical complications. STUDY DESIGN: Retrospective. METHODS: Medical records of horses diagnosed with THO were retrieved, and signalment, clinical signs and duration, presence of corneal ulceration and bilateral occurrence were recorded...
May 18, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28508402/risk-factors-for-human-immunodeficiency-virus-among-blood-donors-in-cameroon-evidence-for-the-design-of-an-africa-specific-donor-history-questionnaire
#11
Claude T Tagny, Georges Nguefack-Tsague, Diderot Fopa, Celestin Ashu, Estel Tante, Pauline Ngo Balogog, Olivier Donfack, Dora Mbanya, Syria Laperche, Edward Murphy
BACKGROUND: In sub-Saharan Africa improving the deferral of at-risk blood donors would be a cost-effective approach to reducing transfusion-transmitted human immunodeficiency virus (HIV) infections. We performed a pilot case-control study to identify the risk factors for HIV infection and to develop an adapted donor history questionnaire (DHQ) for sub-Saharan Africa. STUDY DESIGN AND METHODS: We recruited 137 HIV-positive donors (cases) and 256 HIV-negative donors (controls) and gathered risk factor data using audio computer-assisted self-interview...
May 15, 2017: Transfusion
https://www.readbyqxmd.com/read/28494874/molecular-subtype-specific-biomarkers-improve-prediction-of-prognosis-in-colorectal-cancer
#12
Jesper Bertram Bramsen, Mads Heilskov Rasmussen, Halit Ongen, Trine Block Mattesen, Mai-Britt Worm Ørntoft, Sigrid Salling Árnadóttir, Juan Sandoval, Teresa Laguna, Søren Vang, Bodil Øster, Philippe Lamy, Mogens Rørbæk Madsen, Søren Laurberg, Manel Esteller, Emmanouil Theophilos Dermitzakis, Torben Falck Ørntoft, Claus Lindbjerg Andersen
Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC into natural molecular subtypes; however, this strategy is not yet able to provide clinicians with improved tools for decision making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including >300 previously unpublished samples, we identify cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the microbiome...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28492093/higher-prevalence-of-cerebral-white-matter-hyperintensities-in-homozygous-apoe-%C3%A9-4-allele-carriers-aged-45-75-results-from-the-alfa-study
#13
Santiago Rojas, Anna Brugulat-Serrat, Nuria Bargalló, Carolina Minguillón, Alan Tucholka, Carles Falcon, Andreia Carvalho, Sebastian Morán, Manel Esteller, Nina Gramunt, Karine Fauria, Jordi Camí, José L Molinuevo, Juan D Gispert
Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28476014/advanced-paternal-age-is-associated-with-earlier-schizophrenia-onset-in-offspring-results-from-the-national-multicentric-face-sz-cohort
#14
Guillaume Fond, Ophélia Godin, Laurent Boyer, Pierre-Michel Llorca, Meja Andrianarisoa, Lore Brunel, Bruno Aouizerate, Fabrice Berna, Delphine Capdevielle, Thierry D'Amato, Hélène Denizot, Caroline Dubertret, Julien Dubreucq, Catherine Faget, Franck Gabayet, Jasmina Mallet, David Misdrahi, Christine Passerieux, Romain Rey, Raphaelle Richieri, Aurélie Schandrin, Mathieu Urbach, Pierre Vidailhet, Marion Leboyer, Ewa Bulzacka, Franck Schürhoff, Meja Andrianarisoa, Bruno Aouizerate, Fabrice Berna, Olivier Blanc, Lore Brunel, Ewa Bulzacka, Delphine Capdevielle, Isabelle Chereau-Boudet, Géraldine Chesnoy-Servanin, Jean-Michel Danion, Thierry D'Amato, Arnaud Deloge, Céline Delorme, Hélène Denizot, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Catherine Faget, Cécile Fluttaz, Guillaume Fond, Sophie Fonteneau, Franck Gabayet, Elisabeth Giraud-Baro, Marie-Christine Hardy-Bayle, Lacelle Delphine, Christophe Lançon, Hakim Laouamri, Marion Leboyer, Tifenn Le Gloahec, Yann Le Strat, Pierre-Michel Llorca, Jasmina Mallet, Emeline Metairie, David Misdrahi, Isabelle Offerlin-Meyer, Christine Passerieux, Pauline Peri, Sylvie Pires, Céline Portalier, Romain Rey, Céline Roman, Aurélie Schandrin, Franck Schürhoff, Arnaud Tessier, Anne-Marie Tronche, Mathieu Urbach, Florence Vaillant, Aurélie Vehier, Pierre Vidailhet, Estel Vilà, Hanan Yazbek, Anna Zinetti-Bertschy
The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort...
April 12, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28471259/epidemiology-of-systemic-lupus-erythematosus
#15
Guillermo J Pons-Estel, Manuel F Ugarte-Gil, Graciela S Alarcón
Systemic lupus erythematosus (SLE) is a disease distributed worldwide, which occurs in both genders, and across racial/ethnic and age groups; however, higher rates are observed in adults, in women and in non-Caucasians. Genetic, environmental, sociodemographic and methodological issues are responsible not only for these differences but for the variable course and outcome of the disease. Non-Caucasians have a more severe disease with a higher risk for early mortality and damage accrual. Males also have a more severe disease; however, a negative impact of male gender on lupus outcomes has not been firmly established...
May 16, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28457887/resistance-to-taxanes-in-triple-negative-breast-cancer-associates-with-the-dynamics-of-a-cd49f-tumor-initiating-population
#16
Jorge Gómez-Miragaya, Marta Palafox, Laia Paré, Guillermo Yoldi, Irene Ferrer, Sergi Vila, Patricia Galván, Pasquale Pellegrini, Hector Pérez-Montoyo, Ana Igea, Purificación Muñoz, Manel Esteller, Angel R Nebreda, Ander Urruticoechea, Idoia Morilla, Sonia Pernas, Fina Climent, María Teresa Soler-Monso, Ana Petit, Violeta Serra, Aleix Prat, Eva González-Suárez
Taxanes are a mainstay of treatment for breast cancer, but resistance often develops followed by metastatic disease and mortality. Aiming to reveal the mechanisms underlying taxane resistance, we used breast cancer patient-derived orthoxenografts (PDX). Mimicking clinical behavior, triple-negative breast tumors (TNBCs) from PDX models were more sensitive to docetaxel than luminal tumors, but they progressively acquired resistance upon continuous drug administration. Mechanistically, we found that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands during the acquisition of drug resistance...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28442560/obesity-and-menopause-modify-the-epigenomic-profile-of-breast-cancer
#17
Ana B Crujeiras, Angel Díaz-Lagares, Olafur A Stefansson, Manuel Macias, Juan Sandoval, Juan Cueva, Rafael López-López, Sebastian Moran, Jon G Jonasson, Laufey Tryggvadottir, Elinborg Olafsdottir, Francisco J Tinahones, Marcos C Carreira, Felipe F Casanueva, Manel Esteller
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumor were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28420071/pleuropulmonary-involvement-in-patients-with-systemic-lupus-erythematosus-from-a-latin-american-inception-cohort-gladel
#18
M J Haye Salinas, F Caeiro, V Saurit, A Alvarellos, D Wojdyla, H R Scherbarth, A C de O E Silva, J C Tavares Brenol, L T Lavras Costallat, O J Neira, A Iglesias Gamarra, G Vásquez, G A Reyes Llerena, L A Barile-Fabris, L H Silveira, M J Sauza Del Pozo, E M Acevedo Vásquez, J L Alfaro Lozano, M H Esteva Spinetti, G S Alarcón, B A Pons-Estel
Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28396363/genomic-and-molecular-screenings-identify-different-mechanisms-for-acquired-resistance-to-met-inhibitors-in-lung-cancer-cells
#19
Pol Gimenez-Xavier, Eva Pros, Ester Bonastre, Sebastian Moran, Ana Aza, Osvaldo Graña, Gonzalo Gomez-Lopez, Sophia Derdak, Marc Dabad, Anna Esteve-Codina, Jose R Hernandez Mora, Diana Salinas-Chaparro, Manel Esteller, David Pisano, Montse Sanchez-Cespedes
The development of resistance to tyrosine kinase inhibitors (TKI) limits the long-term efficacy of cancer treatments involving them. We aimed to understand the mechanisms that underlie acquired resistance (AR) to MET inhibitors in lung cancer. EBC1 cells, which have MET amplification and are sensitive to TKIs against MET, were used to generate multiple clones with AR to a MET-TKI. Whole-exome sequencing, RNA sequencing, and global DNA methylation analysis were used to scrutinize the genetic and molecular characteristics of the resistant cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28370075/cancer-incidence-after-initiation-of-antimuscarinic-medications-for-overactive-bladder-in-the-united-kingdom-evidence-for-protopathic-bias
#20
James A Kaye, Andrea V Margulis, Joan Fortuny, Lisa J McQuay, Estel Plana, Jennifer L Bartsch, Christine L Bui, Susana Perez-Gutthann, Alejandro Arana
STUDY OBJECTIVE: To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs). DESIGN: Retrospective cohort study. DATA SOURCE: United Kingdom's Clinical Practice Research Datalink. PATIENTS: A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012...
March 31, 2017: Pharmacotherapy
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