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https://www.readbyqxmd.com/read/28925175/dream-to-become-dr-canady-inspires-an-aspiring-surgeon
#1
Estell Williams
No abstract text is available yet for this article.
February 2017: Bulletin of the American College of Surgeons
https://www.readbyqxmd.com/read/28924151/dna-methylomes-reveal-biological-networks-involved-in-human-eye-development-functions-and-associated-disorders
#2
María Berdasco, Antonio Gómez, Marcos J Rubio, Jaume Català-Mora, Vicente Zanón-Moreno, Miguel Lopez, Cristina Hernández, Shigeo Yoshida, Takahito Nakama, Keijiro Ishikawa, Tatsuro Ishibashi, Amina M Boubekeur, Lotfi Louhibi, Miguel A Pujana, Sergi Sayols, Fernando Setien, Dolores Corella, Carmen de Torres, Andreu Parareda, Jaume Mora, Ling Zhao, Kang Zhang, Matilde E Lleonart, Javier Alonso, Rafael Simó, Josep M Caminal, Manel Esteller
This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919484/lung-cancer-epigenetics-from-knowledge-to-applications
#3
REVIEW
Michaël Duruisseaux, Manel Esteller
Lung cancer is the leading cause of cancer-related mortality worldwide. Advances in our understanding of the genomics of lung cancer have led to substantial progress in the treatment of specific molecular subsets. Immunotherapy also emerges as a major breakthrough in lung cancer treatment. However, challenges remain as a consensual approach for early lung cancer detection remains elusive while primary or secondary drug resistance eventually leads to treatment failure in all patients with advanced disease. Furthermore, a large portion of patients are still treated with conventional chemotherapy that is only modestly effective...
September 14, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28883545/copy-number-rather-than-epigenetic-alterations-are-the-major-dictator-of-imprinted-methylation-in-tumors
#4
Alex Martin-Trujillo, Enrique Vidal, Ana Monteagudo-Sa Nchez, Marta Sanchez-Delgado, Sebastian Moran, Jose Ramon Hernandez Mora, Holger Heyn, Miriam Guitart, Manel Esteller, David Monk
It has been postulated that imprinting aberrations are common in tumors. To understand the role of imprinting in cancer, we have characterized copy-number and methylation in over 280 cancer cell lines and confirm our observations in primary tumors. Imprinted differentially methylated regions (DMRs) regulate parent-of-origin monoallelic expression of neighboring transcripts in cis. Unlike single-copy CpG islands that may be prone to hypermethylation, imprinted DMRs can either loose or gain methylation during tumorigenesis...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28882223/micrornas-and-epigenetics
#5
Catia Moutinho, Manel Esteller
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression mainly at the posttranscriptional level. Similar to protein-coding genes, their expression is also controlled by genetic and epigenetic mechanisms. Disruption of these control processes leads to abnormal expression of miRNAs in cancer. In this chapter, we discuss the supportive links between miRNAs and epigenetics in the context of carcinogenesis. miRNAs can be epigenetically regulated by DNA methylation and/or specific histone modifications...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/28881673/bromodomain-inhibition-shows-antitumoral-activity-in-mice-and-human-luminal-breast-cancer
#6
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)...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28857715/predictive-factors-of-flares-in-systemic-lupus-erythematosus-patients-data-from-a-multiethnic-latin-american-cohort
#7
M F Ugarte-Gil, D Wojdyla, C A Pastor-Asurza, R V Gamboa-Cárdenas, E M Acevedo-Vásquez, L J Catoggio, M A García, E Bonfá, E I Sato, L Massardo, V Pascual-Ramos, L A Barile, G Reyes-Llerena, A Iglesias-Gamarra, J F Molina-Restrepo, R Chacón-Díaz, G S Alarcón, B A Pons-Estel
Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28838480/self-expanding-versus-balloon-expandable-stents-for-iliac%C3%A2-artery%C3%A2-occlusive-disease-the%C3%A2-randomized-ice-trial
#8
Hans Krankenberg, Thomas Zeller, Maja Ingwersen, Josefin Schmalstieg, Hans Martin Gissler, Sigrid Nikol, Iris Baumgartner, Nicolas Diehm, Estell Nickling, Stefan Müller-Hülsbeck, Rainer Schmiedel, Giovanni Torsello, Willibald Hochholzer, Christian Stelzner, Klaus Brechtel, Wulf Ito, Ralph Kickuth, Erwin Blessing, Marcus Thieme, Jaroslaw Nakonieczny, Thomas Nolte, Ragnar Gareis, Harald Boden, Sebastian Sixt
OBJECTIVES: Atherosclerosis of iliac arteries is widespread. As inflow vessels, they are of great clinical significance and increasingly being treated by endovascular means. Most commonly, stents are implanted. BACKGROUND: So far, due to a lack of comparative data, no guideline recommendations on the preferable stent type, balloon-expandable stent (BE) or self-expanding stent (SE), have been issued. METHODS: In this randomized, multicenter study, patients with moderate to severe claudication from common or external iliac artery occlusive disease were assigned 1:1 to either BE or SE...
August 28, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28741488/extraordinary-cancer-epigenomics-thinking-outside-the-classical-coding-and-promoter-box
#9
REVIEW
Matthew Murtha, Manel Esteller
The advent of functional genomics powered by high-throughput sequencing has given us a new appreciation of the genomic sequences that lie outside the canonical promoter-coding sequence box. These regions harbor distant regulatory elements, enhancers, super-enhancers, insulators, alternative promoters, and sequences that transcribe as noncoding RNAs (ncRNAs) such as miRNAs and long ncRNAs. These functional genomics studies have also enabled a clearer understanding of the role of the 3D structure of the genome in epigenetic regulation...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28734945/the-epigenomic-revolution-in-breast-cancer-from-single-gene-to-genome-wide-next-generation-approaches
#10
REVIEW
Veronica Davalos, Anna Martinez-Cardus, Manel Esteller
From the first identification of aberrant DNA methylation in primary tumors in humans >3 decades ago, progress in cancer epigenetics research has been exponential. For many years, cancer epigenetics studies relied on the identification of DNA methylation and histone modifications at specific genes. Those studies laid the foundation for the field and revealed the epigenetic alterations as a hallmark of cancer, as well as the crucial role of epigenetic mechanisms in tumorigenesis. The introduction of next-generation sequencing and array-based technologies for analyzing epigenetic states has accelerated our understanding about cancer and have become potent tools in our fight against the disease...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#11
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28716465/fibroblast-like-synoviocyte-mechanosensitivity-to-fluid-shear-is-modulated-by-interleukin-1%C3%AE
#12
Eben G Estell, Lance A Murphy, Amy M Silverstein, Andrea R Tan, Roshan P Shah, Gerard A Ateshian, Clark T Hung
Fibroblast-like synoviocytes (FLS) reside in the synovial membrane of diarthrodial joints and are exposed to a dynamic fluid environment that presents both physical and chemical stimuli. The ability of FLS to sense and respond to these stimuli plays a key role in their normal function, and is implicated in the alterations to function that occur in osteoarthritis (OA). The present work characterizes the response of FLS to fluid flow-induced shear stress via real-time calcium imaging, and tests the hypothesis that this response is modulated by interleukin-1α (IL-1α), a cytokine elevated in OA...
June 28, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28714469/transancestral-mapping-and-genetic-load-in-systemic-lupus-erythematosus
#13
Carl D Langefeld, Hannah C Ainsworth, Deborah S Cunninghame Graham, Jennifer A Kelly, Mary E Comeau, Miranda C Marion, Timothy D Howard, Paula S Ramos, Jennifer A Croker, David L Morris, Johanna K Sandling, Jonas Carlsson Almlöf, Eduardo M Acevedo-Vásquez, Graciela S Alarcón, Alejandra M Babini, Vicente Baca, Anders A Bengtsson, Guillermo A Berbotto, Marc Bijl, Elizabeth E Brown, Hermine I Brunner, Mario H Cardiel, Luis Catoggio, Ricard Cervera, Jorge M Cucho-Venegas, Solbritt Rantapää Dahlqvist, Sandra D'Alfonso, Berta Martins Da Silva, Iñigo de la Rúa Figueroa, Andrea Doria, Jeffrey C Edberg, Emőke Endreffy, Jorge A Esquivel-Valerio, Paul R Fortin, Barry I Freedman, Johan Frostegård, Mercedes A García, Ignacio García de la Torre, Gary S Gilkeson, Dafna D Gladman, Iva Gunnarsson, Joel M Guthridge, Jennifer L Huggins, Judith A James, Cees G M Kallenberg, Diane L Kamen, David R Karp, Kenneth M Kaufman, Leah C Kottyan, László Kovács, Helle Laustrup, Bernard R Lauwerys, Quan-Zhen Li, Marco A Maradiaga-Ceceña, Javier Martín, Joseph M McCune, David R McWilliams, Joan T Merrill, Pedro Miranda, José F Moctezuma, Swapan K Nath, Timothy B Niewold, Lorena Orozco, Norberto Ortego-Centeno, Michelle Petri, Christian A Pineau, Bernardo A Pons-Estel, Janet Pope, Prithvi Raj, Rosalind Ramsey-Goldman, John D Reveille, Laurie P Russell, José M Sabio, Carlos A Aguilar-Salinas, Hugo R Scherbarth, Raffaella Scorza, Michael F Seldin, Christopher Sjöwall, Elisabet Svenungsson, Susan D Thompson, Sergio M A Toloza, Lennart Truedsson, Teresa Tusié-Luna, Carlos Vasconcelos, Luis M Vilá, Daniel J Wallace, Michael H Weisman, Joan E Wither, Tushar Bhangale, Jorge R Oksenberg, John D Rioux, Peter K Gregersen, Ann-Christine Syvänen, Lars Rönnblom, Lindsey A Criswell, Chaim O Jacob, Kathy L Sivils, Betty P Tsao, Laura E Schanberg, Timothy W Behrens, Earl D Silverman, Marta E Alarcón-Riquelme, Robert P Kimberly, John B Harley, Edward K Wakeland, Robert R Graham, Patrick M Gaffney, Timothy J Vyse
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28699354/drug-mediated-intracellular-donation-of-nitric-oxide-potently-inhibits-5-lipoxygenase-a-possible-key-to-future-anti-leukotriene-therapy
#14
Jessica Roos, Marcus Peters, Isabelle V Maucher, Benjamin Kühn, Jasmin Fettel, Nadine Hellmuth, Camilla Brat, Benita Sommer, Anja Urbschat, Matthias Piesche, Anja Vogel, Ewgenij Proschak, René Blöcher, Estel la Buscato, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten Jürgen Maier
AIMS: 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis and cancer. Because 5-LO contains critical nucleophilic amino acids, which are sensitive to electrophilic modifications, we determined the consequences of a drug-mediated intracellular release of nitric oxide (NO) on 5-LO product formation by human granulocytes and on 5-LO-dependent pulmonary inflammation in vivo...
July 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28692793/rare-x-chromosome-abnormalities-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome
#15
Rohan Sharma, Valerie M Harris, Joshua Cavett, Biji T Kurien, Ke Liu, Kristi A Koelsch, Anum Fayaaz, Kaustubh S Chaudhari, Lida Radfar, David Lewis, Donald U Stone, C Erick Kaufman, Shibo Li, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Jennifer A Kelly, Bernardo Pons-Estel, Roland Jonsson, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Marta Alarcon-Riquelme, Xavier Mariette, Christopher J Lessard, John B Harley, Wan-Fai Ng, Astrid Rasmussen, Kathy L Sivils, R Hal Scofield
BACKGROUND: Sjögren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease suggesting a dose effect on the X chromosome. METHODS: We examined cohorts of Sjögren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects...
July 10, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28678681/profiling-of-oxbs-450k-5-hydroxymethylcytosine-in-human-placenta-and-brain-reveals-enrichment-at-imprinted-loci
#16
Jose Ramon Hernandez Mora, Marta Sanchez-Delgado, Paolo Petazzi, Sebastian Moran, Manel Esteller, Isabel Iglesias-Platas, David Monk
DNA methylation (5-methylcytosine, 5mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28675165/precision-medicine-based-on-epigenomics-the-paradigm-of-carcinoma-of-unknown-primary
#17
REVIEW
Sebastián Moran, Anna Martinez-Cardús, Stergios Boussios, Manel Esteller
Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP...
July 4, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28670349/epigenetic-mechanisms-during-ageing-and-neurogenesis-as-novel-therapeutic-avenues-in-human-brain-disorders
#18
REVIEW
Raúl Delgado-Morales, Roberto Carlos Agís-Balboa, Manel Esteller, María Berdasco
Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28624801/bromodomain-inhibition-shows-antitumoral-activity-in-mice-and-human-luminal-breast-cancer
#19
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
#20
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 & 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...
September 2017: Gastroenterology
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