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https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#1
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly over-expressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1 and VEGF...
March 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28319067/the-histone-demethylase-kdm3a-and-its-downstream-target-mcam-promote-ewing-sarcoma-cell-migration-and-metastasis
#2
M Sechler, J K Parrish, D K Birks, P Jedlicka
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318118/distinct-expression-of-nk2-homeobox-1-nkx2-1-and-goblet-cell-hyperplasia-in-nasal-polyps-with-different-endotypes
#3
Jintao Du, Luo Ba, Bo Li, Feng Liu, Xianting Hu, Jie Zhang, Yafeng Liu, Junming Xian, Sixi Liu, Huabin Li
BACKGROUND: Decreased expression of airway epithelial-specific transcription factor NK2 homeobox 1 (NKX2-1) was associated with allergic inflammation in asthma patients. However, the expression and role of NKX2-1 in nasal polyps (NPs) with different endotypes were undefined yet. METHODS: We examined the expression of key cytokines (interleukin [IL]-4 IL-5, IL-13, and IL-17A, etc.) and NKX2-1 in NPs with different endotypes and control tissues by immunohistochemistry staining, qualitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis...
March 20, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#4
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314835/endocrine-therapy-in-the-current-management-of-postmenopausal-estrogen-receptor-positive-metastatic-breast-cancer
#5
Virginia G Kaklamani, William J Gradishar
Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone-responsive and estrogen receptor-positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone-responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen-receptor modulation, aromatase inhibition, and selective estrogen-receptor degradation...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28301293/signatures-of-dna-target-selectivity-by-ets-transcription-factors
#6
Gregory M K Poon, Hye Mi Kim
The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation...
March 16, 2017: Transcription
https://www.readbyqxmd.com/read/28296403/distinct-roles-for-interfacial-hydration-in-site-specific-dna-recognition-by-ets-family-transcription-factors
#7
Suela Xhani, Shingo Esaki, Kenneth Huang, Noa Erlitzki, Gregory M K Poon
The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. Unlike other ETS homologs, such as Ets-1, DNA recognition by PU.1 is highly sensitive to its osmotic environment due to excess interfacial hydration in the complex. To interrogate interfacial hydration in the two homologs, we mutated a highly conserved tyrosine residue, which is exclusively engaged in coordinating a well-defined water contact between the protein and DNA among ETS proteins, to phenylalanine...
March 15, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28293523/comparison-of-peripheral-nerve-regeneration-with-side-to-side-end-to-side-and-end-to-end-repairs-an-experimental-study
#8
Henrikki Rönkkö, Harry Göransson, Hanna-Stiina Taskinen, Pasi Paavilainen, Tero Vahlberg, Matias Röyttä
BACKGROUND: The present study was conducted to find out a tool to enable improved functional recovery with proximal nerve injury. In this experimental study, nerve regeneration was compared between side-to-side (STS), end-to-side (ETS), and end-to-end repairs. METHODS: The walk track analysis was used as an outcome of functional recovery. Nerve regeneration was studied with morphometry and histology 6 or 26 weeks postoperatively. RESULTS: All 3 repair techniques showed regeneration of the nerve...
December 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28292614/embryo-transfer-simulation-improves-pregnancy-rates-and-decreases-time-to-proficiency-in-reproductive-endocrinology-and-infertility-fellow-embryo-transfers
#9
Ryan J Heitmann, Micah J Hill, John M Csokmay, Justin Pilgrim, Alan H DeCherney, Shad Deering
OBJECTIVE: To design and evaluate an ET simulator to train Reproductive Endocrinology and Infertility (REI) fellows' techniques of ET. DESIGN: Simulation model development and retrospective cohort analysis. SETTING: Not applicable. PATIENT(S): Patients undergoing IVF. INTERVENTION(S): Simulation model evaluation and implementation of ET simulation training. MAIN OUTCOME MEASURE(S): Pregnancy rates...
March 11, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28292442/eto2-glis2-hijacks-transcriptional-complexes-to-drive-cellular-identity-and-self-renewal-in-pediatric-acute-megakaryoblastic-leukemia
#10
Cécile Thirant, Cathy Ignacimouttou, Cécile K Lopez, M'Boyba Diop, Lou Le Mouël, Clarisse Thiollier, Aurélie Siret, Phillipe Dessen, Zakia Aid, Julie Rivière, Philippe Rameau, Céline Lefebvre, Mehdi Khaled, Guy Leverger, Paola Ballerini, Arnaud Petit, Hana Raslova, Catherine L Carmichael, Benjamin T Kile, Eric Soler, John D Crispino, Christian Wichmann, Françoise Pflumio, Jürg Schwaller, William Vainchenker, Camille Lobry, Nathalie Droin, Olivier A Bernard, Sébastien Malinge, Thomas Mercher
Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 and GLIS2 domains are required to drive increased self-renewal properties. ETO2-GLIS2 directly binds DNA to control transcription of associated genes by upregulation of expression and interaction with the ETS-related ERG protein at enhancer elements...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28292236/microwave-assisted-olefin-metathesis-as-pivotal-step-in-the-synthesis-of-bioactive-compounds
#11
Koffi Sénam Etsè, Alice Ngendera, Nelly Tshibalonza Ntumba, Albert Demonceau, Lionel Delaude, Ileana Dragutan, Valerian Dragutan
Over the last two decades, olefin metathesis has emerged as a new avenue in the design of new routes for the synthesis of natural products and active pharmaceutical ingredients. In many cases, syntheses based on olefin metathesis strategies provide elegant routes in terms of increasing the overall yields, improving the synthesis scope, and decreasing the number of steps. On the other hand, over the last decade, microwave-assisted chemistry has experienced an incredible development, which rapidly opened new vistas in organic synthesis and in homogeneous catalysis...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28282237/associations-of-common-noncommunicable-medical-conditions-and-chronic-diseases-with-chronotype-in-a-population-based-health-examination-study
#12
Syaron Basnet, Ilona Merikanto, Tuuli Lahti, Satu Männistö, Tiina Laatikainen, Erkki Vartiainen, Timo Partonen
Chronotype is an emerging predictor of health and longevity, and understanding its influence on chronic diseases is important for constructing conceptual models of long-term pathways to health. We assessed the associations of chronotype with health status in the general Finnish adult population. Our population-based data were derived from the National FINRISK 2012 study and consisted of 4414 participants, aged 25-74 years, living in Finland. As part of their health examination, participants were asked about their circadian preference to the daily activities (morningness-eveningness) and a diagnosis or treatment for a set of common noncommunicable medical conditions and chronic diseases during the past 12 months...
March 10, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28280716/aflatoxin-b1-induces-reactive-oxygen-species-mediated-autophagy-and-extracellular-trap-formation-in-macrophages
#13
Yanan An, Xiaochen Shi, Xudong Tang, Yang Wang, Fengge Shen, Qiaoli Zhang, Chao Wang, Mingguo Jiang, Mingyuan Liu, Lu Yu
Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28280092/a-phase-i-ib-study-of-enzalutamide-alone-and-in-combination-with-endocrine-therapies-in-women-with-advanced-breast-cancer
#14
Lee S Schwartzberg, Denise Yardley, Anthony Elias, Manish Patel, Patricia M LoRusso, Howard A Burris, Ayca Gucalp, Amy Peterson, Martha Blaney, Joyce Steinberg, Jacqueline Gibbons, Tiffany A Traina
PURPOSE: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ETs). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28279709/vegf-signaling-promotes-vascular-endothelial-differentiation-by-modulating-etv2-expression
#15
Satish Casie Chetty, Megan S Rost, Jacob Ryan Enriquez, Jennifer A Schumacher, Kristina Baltrunaite, Andrea Rossi, Didier Y R Stainier, Saulius Sumanas
Vasculogenesis involves the differentiation of vascular endothelial progenitors de novo from undifferentiated mesoderm, their migration and coalescence to form the major embryonic vessels and the acquisition of arterial or venous identity. Vascular Endothelial Growth Factor (Vegf) signaling plays multiple roles during vascular development. However, its function during embryonic vasculogenesis has been controversial. Previous studies have implicated Vegf signaling in either regulating arteriovenous specification or overall vascular endothelial differentiation...
March 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28276961/skill-clusters-of-ability-to-manage-everyday-technology-among-people-with-and-without-cognitive-impairment-dementia-and-acquired-brain-injury
#16
Camilla Malinowsky, Mandana Fallahpour, Maria Larsson Lund, Louise Nygård, Anders Kottorp
BACKGROUND: In order to develop supporting interventions for people demonstrating problems ET use, a detailed level of description of strengths and deficits is needed. AIMS: To explore clusters of specific performance skill required when using ET, and to evaluate if and in what way such clusters are associated with age, gender, diagnosis, and types of ETs managed. MATERIALS AND METHODS: A secondary analysis of 661 data records from 203 heterogeneous samples of participants using the Management of Everyday Technology Assessment (META) was used...
March 2, 2017: Scandinavian Journal of Occupational Therapy
https://www.readbyqxmd.com/read/28275352/corrigendum-sustained-contraction-in-vascular-smooth-muscle-by-activation-of-l-type-ca-2-channels-does-not-involve-ca-2-sensitization-or-caldesmon
#17
Hillevi K Ets, Chun Y Seow, Robert S Moreland
[This corrects the article on p. 516 in vol. 7, PMID: 28082901.].
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28275002/high-constitutive-activity-of-a-broad-panel-of-housekeeping-and-tissue-specific-cis-regulatory-elements-depends-on-a-subset-of-ets-proteins
#18
Alessia Curina, Alberto Termanini, Iros Barozzi, Elena Prosperini, Marta Simonatto, Sara Polletti, Alessio Silvola, Monica Soldi, Liv Austenaa, Tiziana Bonaldi, Serena Ghisletti, Gioacchino Natoli
Enhancers and promoters that control the transcriptional output of terminally differentiated cells include cell type-specific and broadly active housekeeping elements. Whether the high constitutive activity of these two groups of cis-regulatory elements relies on entirely distinct or instead also on shared regulators is unknown. By dissecting the cis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 base pairs (bp) from the transcription start sites of highly active housekeeping genes...
March 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28273617/toxic-effects-of-the-antihistamine-cetirizine-in-mussel-mytilus-galloprovincialis
#19
Miguel Teixeira, Ângela Almeida, Vânia Calisto, Valdemar I Esteves, Rudolf J Schneider, Frederick J Wrona, Amadeu M V M Soares, Etelvina Figueira, Rosa Freitas
Recent studies have become increasingly focused on the assessment of pharmaceuticals occurrence in aquatic ecosystems, however the potential toxicity to non-target organisms is still largely unknown. The antihistamine cetirizine is a commonly used pharmaceutical, already detected in surface waters of marine aquatic systems worldwide. In the present study Mytilus galloprovincialis mussels were exposed to a range of cetirizine concentrations (0.3, 3.0, 6.0 and 12.0 μg/L), resembling moderate to highly contaminated areas, over 28 days...
March 5, 2017: Water Research
https://www.readbyqxmd.com/read/28264194/rheological-separation-of-the-megathrust-seismogenic-zone-and-episodic-tremor-and-slip
#20
Xiang Gao, Kelin Wang
Episodic tremor and accompanying slow slip, together called ETS, is most often observed in subduction zones of young and warm subducting slabs. ETS should help us to understand the mechanics of subduction megathrusts, but its mechanism is still unclear. It is commonly assumed that ETS represents a transition from seismic to aseismic behaviour of the megathrust with increasing depth, but this assumption is in contradiction with an observed spatial separation between the seismogenic zone and the ETS zone. Here we propose a unifying model for the necessary geological condition of ETS that explains the relationship between the two zones...
March 6, 2017: Nature
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