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https://www.readbyqxmd.com/read/28489605/genetic-rearrangements-result-in-altered-gene-expression-and-novel-fusion-transcripts-in-s%C3%A3-zary-syndrome
#1
Katarzyna Iżykowska, Grzegorz K Przybylski, Claudia Gand, Floriane C Braun, Piotr Grabarczyk, Andreas W Kuss, Karolina Olek-Hrab, Armando N Bastidas Torres, Maarten H Vermeer, Willem H Zoutman, Cornelis P Tensen, Christian A Schmidt
Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480263/diagnosis-in-france-of-a-non-toxigenic-tox-gene-bearing-strain-of-corynebacterium-diphtheriae-in-a-young-male-back-from-senegal
#2
Typhaine Billard-Pomares, Cécile Rouyer, Violaine Walewski, Edgar Badell-Ocando, Marc Dumas, Coralie Zumelzu, Françoise Jaureguy, Sylvain Brisse, Frédéric Caux, Olivier Bouchaud, Etienne Carbonnelle
Cutaneous diphtheria is uncommon in Europe. In this study, we report a case of imported cutaneous infection due to a non-toxigenic but tox gene-bearing (NTTB) strain of Corynebacterium diphtheriae. The NTTB strains are recognized as emerging pathogens across Europe, and physicians and bacteriologists should be aware of the circulation of these strains.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28469408/modification-of-s-adenosyl-l-homocysteine-as-inhibitor-of-nonstructural-protein-5-methyltransferase-dengue-virus-through-molecular-docking-and-molecular-dynamics-simulation
#3
Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami
Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test...
2017: Drug Target Insights
https://www.readbyqxmd.com/read/28464377/bile-salts-and-alkaline-ph-reciprocally-modulate-the-interaction-between-the-periplasmic-domains-of-vibrio-cholerae-toxr-and-toxs
#4
Charles R Midgett, Salvador Almagro-Moreno, Maria Pellegrini, Ronald K Taylor, Karen Skorupski, F Jon Kull
ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood...
May 2, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28441483/discovery-of-a-novel-class-of-survival-motor-neuron-2-splicing-modifiers-for-the-treatment-of-spinal-muscular-atrophy
#5
Emmanuel Pinard, Luke Green, Michael Reutlinger, Marla Weetall, Nikolai A Naryshkin, John Baird, Karen S Chen, Sergey V Paushkin, Friedrich Metzger, Hasane Ratni
Spinal muscular atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene, resulting in low levels of functional SMN protein. We have reported recently the identification of small molecules (coumarins, iso-coumarins and pyrido-pyrimidinones) that modify the alternative splicing of SMN2, a paralogous gene to SMN1, restoring the survival motor neuron (SMN) protein level in mouse models of SMA. Herein, we report our efforts to identify a novel chemotype as one strategy to potentially circumvent safety concerns from earlier derivatives such as in vitro phototoxicity and in vitro mutagenicity associated with compounds 1 and 2 or the in vivo retinal findings observed in a long-term chronic tox study with 3 at high exposures only...
May 4, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28395759/a-multicenter-phase-ii-study-of-personalized-folfiri-cetuximab-for-safe-dose-intensification
#6
Michèle Boisdron-Celle, Jean Philippe Metges, Olivier Capitain, Antoine Adenis, Jean Luc Raoul, Thierry Lecomte, You Heng Lam, Roger Faroux, Claude Masliah, Anne Lise Poirier, Virginie Berger, Alain Morel, Erick Gamelin
We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU(ODPM Tox)) followed by PK-guided dose optimization (5-FU(ODPM Protocol))...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28395758/prevention-of-5-fluorouracil-induced-early-severe-toxicity-by-pre-therapeutic-dihydropyrimidine-dehydrogenase-deficiency-screening-assessment-of-a-multiparametric-approach
#7
Michele Boisdron-Celle, Olivier Capitain, Roger Faroux, Christophe Borg, Jean Philippe Metges, Marie Pierre Galais, Mehdi Kaassis, Jaafar Bennouna, Karine Bouhier-Leporrier, Eric Francois, Isabelle Baumgaertner, Véronique Guerin-Meyer, Oana Cojocarasu, Celia Roemer-Becuwe, Claire Stampfli, Ludovic Rosenfeld, Thierry Lecompte, Virginie Berger, Alain Morel, Erick Gamelin
5-Fluorouracil (5-FU)-based treatments can lead to early-onset severe (4%-5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28371489/a-strategy-to-accelerate-protein-production-from-a-pool-of-clones-in-chinese-hamster-ovary-cells-for-toxicology-studies
#8
Zhilan Hu, Wendy Hsu, Abby Pynn, Domingos Ng, Donna Quicho, Yilma Adem, Zephie Kwong, Brad Mauger, John Joly, Bradley Snedecor, Michael W Laird, Dana C Andersen, Amy Shen
In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for Investigational New Drug (IND)-enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND-enabling toxicology studies ("Pool for Tox strategy") during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately four months at Genentech), leading to a potential acceleration of four months for the IND submission...
April 3, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28350787/quality-adjusted-survival-with-combination-nal-iri-5-fu-lv-vs-5-fu-lv-alone-in-metastatic-pancreatic-cancer-patients-previously-treated-with-gemcitabine-based-therapy-a-q-twist-analysis
#9
Uwe Pelzer, Jean-Frédéric Blanc, Davide Melisi, Antonio Cubillo, Daniel D Von Hoff, Andrea Wang-Gillam, Li-Tzong Chen, Jens T Siveke, Yin Wan, Caitlyn T Solem, Marc F Botteman, Yoojung Yang, Floris A de Jong, Richard A Hubner
BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST)...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28337503/gut-microbiome-related-metabolic-changes-in-plasma-of-antibiotic-treated-rats
#10
C Behr, H Kamp, E Fabian, G Krennrich, W Mellert, E Peter, V Strauss, T Walk, I M C M Rietjens, B van Ravenzwaay
The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites...
March 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28327672/tox-and-adipoq-gene-polymorphisms-are-associated-with-antipsychotic-induced-weight-gain-in-han-chinese
#11
Shen Li, Chengai Xu, Yuan Tian, Xueshi Wang, Rui Jiang, Miaomiao Zhang, Lili Wang, Guifu Yang, Ying Gao, Chenyu Song, Yukun He, Ying Zhang, Jie Li, Wei-Dong Li
To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#12
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295221/regosarc-regorafenib-versus-placebo-in-doxorubicin-refractory-soft-tissue-sarcoma-a-quality-adjusted-time-without-symptoms-of-progression-or-toxicity-analysis
#13
Vincent Berry, Laurent Basson, Emilie Bogart, Olivier Mir, Jean-Yves Blay, Antoine Italiano, François Bertucci, Christine Chevreau, Stéphanie Clisant-Delaine, Bernadette Liegl-Antzager, Emmanuelle Tresch-Bruneel, Jennifer Wallet, Sophie Taieb, Emilie Decoupigny, Axel Le Cesne, Thomas Brodowicz, Nicolas Penel
BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse...
March 10, 2017: Cancer
https://www.readbyqxmd.com/read/28295044/novel-transcriptome-assembly-and-comparative-toxicity-pathway-analysis-in-mahi-mahi-coryphaena-hippurus-embryos-and-larvae-exposed-to-deepwater-horizon-oil
#14
Elvis Genbo Xu, Edward M Mager, Martin Grosell, E Starr Hazard, Gary Hardiman, Daniel Schlenk
The impacts of Deepwater Horizon (DWH) oil on morphology and function during embryonic development have been documented for a number of fish species, including the economically and ecologically important pelagic species, mahi-mahi (Coryphaena hippurus). However, further investigations on molecular events and pathways responsible for developmental toxicity have been largely restricted due to the limited molecular data available for this species. We sought to establish the de novo transcriptomic database from the embryos and larvae of mahi-mahi exposed to water accommodated fractions (HEWAFs) of two DWH oil types (weathered and source oil), in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174041/occurrence-origin-and-toxicity-of-disinfection-byproducts-in-chlorinated-swimming-pools-an-overview
#15
REVIEW
Tarek Manasfi, Bruno Coulomb, Jean-Luc Boudenne
Disinfection treatments are critical to conserve the microbiological quality of swimming pool water and to prevent water-borne infections. The formation of disinfection byproducts (DBPs) in swimming pools is an undesirable consequence resulting from reactions of disinfectants (e.g. chlorine) with organic and inorganic matter present in pool water, mainly brought by bathers. A considerable body of occurrence studies has identified several classes of DBPs in swimming pools with more than 100 compounds detected, mainly in chlorinated freshwater pools...
January 30, 2017: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/28168765/prediction-of-anti-alzheimer-s-activity-of-flavonoids-targeting-acetylcholinesterase-in-silico
#16
Subrata Das, Monjur A Laskar, Satyajit D Sarker, Manabendra D Choudhury, Prakash Roy Choudhury, Abhijit Mitra, Shajarahtunnur Jamil, Siti Mariam A Lathiff, Siti Awanis Abdullah, Norazah Basar, Lutfun Nahar, Anupam D Talukdar
INTRODUCTION: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease. OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease...
February 7, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28168673/case-study-iii-the-construction-of-a-nanotoxicity-database-the-mod-enp-tox-experience
#17
Hanne Vriens, Dominik Mertens, Renaud Regret, Pinpin Lin, Jean-Pierre Locquet, Peter Hoet
The amount of experimental studies on the toxicity of nanomaterials is growing fast. Interpretation and comparison of these studies is a complex issue due to the high amount of variables possibly determining the toxicity of nanomaterials.Qualitative databases providing a structured combination, integration and quality evaluation of the existing data could reveal insights that cannot be seen from different studies alone. A few database initiatives are under development but in practice very little data is publicly available and collaboration between physicists, toxicologists, computer scientists and modellers is needed to further develop databases, standards and analysis tools...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28126528/chromophores-in-operative-surgery-current-practice-and-rationalized-development
#18
REVIEW
Ernest A Azzopardi, Siân-Eleri Owens, Maxwell Murison, Daniel Rees, M Anne Sawhney, Lewis W Francis, R Sofia Rodrigues Teixeira, Marc Clement, R Steven Conlan, Iain S Whitaker
BACKGROUND: Chromophore-containing molecules feature extensively in surgical practice, with synthetic dyes gaining popularity over endogenous optical adjuncts. New applications for chromophores in diagnostics and operative treatment exploit unique chemical structures suited for illuminating target tissues beyond the visual spectrum, ranging from ultraviolet (UV) to near-infrared (NIR). This review outlines the rationale for surgical chromophore application, the weaknesses and risks in each class of these compounds, and areas of foreseeable potential for employment of specialized contrast agents...
January 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28106743/design-synthesis-and-antifungal-activity-evaluation-of-new-thiazolin-4-ones-as-potential-lanosterol-14%C3%AE-demethylase-inhibitors
#19
Anca Stana, Dan C Vodnar, Radu Tamaian, Adrian Pîrnău, Laurian Vlase, Ioana Ionuț, Ovidiu Oniga, Brînduşa Tiperciuc
Twenty-three thiazolin-4-ones were synthesized starting from phenylthioamide or thiourea derivatives by condensation with α-monochloroacetic acid or ethyl α-bromoacetate, followed by substitution in position 5 with various arylidene moieties. All the synthesized compounds were physico-chemically characterized and the IR (infrared spectra), ¹H NMR (proton nuclear magnetic resonance), (13)C NMR (carbon nuclear magnetic resonance) and MS (mass spectrometry) data were consistent with the assigned structures...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28064141/methoxylated-2-hydroxychalcones-as-antiparasitic-hit-compounds
#20
Chiara Borsari, Nuno Santarem, Juan Torrado, Ana Isabel Olías, María Jesús Corral, Catarina Baptista, Sheraz Gul, Markus Wolf, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Philip Gribbon, Jeanette Reinshagen, Pasquale Linciano, Annalisa Tait, Luca Costantino, Lucio H Freitas-Junior, Carolina B Moraes, Pascoalino Bruno Dos Santos, Laura Maria Alcântara, Caio Haddad Franco, Claudia Danielli Bertolacini, Vanessa Fontana, Paloma Tejera Nevado, Joachim Clos, José María Alunda, Anabela Cordeiro-da-Silva, Stefania Ferrari, Maria Paola Costi
Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2'-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, compounds 1, 3, 4, 7 and 8 were the most potent and selective anti-T. brucei compounds (EC50 = 1.3-4.2 μM, selectivity index >10-fold). Compound 4 showed the best early-tox and antiparasitic profile. The pharmacokinetic studies of compound 4 in BALB/c mice using hydroxypropil-β-cyclodextrins formulation showed a 7...
January 27, 2017: European Journal of Medicinal Chemistry
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