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https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#1
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123424/liver-related-morbidity-and-mortality-in-patients-with-chronic-hepatitis-c-and-cirrhosis-with-and-without-sustained-virologic-response
#2
Sofie Hallager, Steen Ladelund, Peer Brehm Christensen, Mette Kjær, Birgit Thorup Roege, Karin Elmegaard Grønbæk, Erika Belard, Toke S Barfod, Lone Galmstrup Madsen, Jan Gerstoft, Britta Tarp, Henrik Bygum Krarup, Nina Weis
Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. Materials and methods: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29090671/targeted-blockade-of-tarp-g8-associated-ampa-receptors-anticonvulsant-activity-with-the-selective-antagonist-ly3130481-cerc-611
#3
Jeffrey M Witkin, Douglas A Schober, Scott D Gleason, John T Catlow, Warren J Porter, Jon Reel, X Jin, J Hobbs, Donald Gehlert, Douglas L Gernert, Kevin M Gardinier, Akihiko S Kato, X Ping, J L Smith
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) g-8 that is under development for epilepsy. The present study provided a broad inquiry into its anticonvulsant properties. LY3130481 was anticonvulsant in multiple acute seizure provocation models in mice and rats. In addition, LY3130481 was effective against absence seizures in the GAERS genetic model and in the Frings mouse model...
November 1, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29073353/trial-characteristics-as-contextual-factors-when-evaluating-targeted-therapies-in-patients-with-psoriatic-disease-a-meta-epidemiological-study
#4
Christine Ballegaard, Tanja S Jørgensen, Marie Skougaard, Vibeke Strand, Philip J Mease, Lars E Kristensen, Lene Dreyer, Alice Gottlieb, Maarten de Wit, Robin Christensen, Simon Tarp
OBJECTIVES: To assess the importance of trial characteristics as contextual factors when evaluating treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis...
October 26, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/29028824/the-association-between-serum-brain-derived-neurotrophic-factor-and-a-cluster-of-cardiovascular-risk-factors-in-adolescents-the-champs-study-dk
#5
Natascha Holbæk Pedersen, Jakob Tarp, Lars Bo Andersen, Anne Kær Gejl, Tao Huang, Lone Peijs, Anna Bugge
BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF) probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors...
2017: PloS One
https://www.readbyqxmd.com/read/29020699/the-first-homemade-colonoscopy-trainer
#6
Dominik Andrzej Walczak, Maciej Grajek, Paulina Agnieszka Walczak, Magdalena Tuliszka-Gołowkin, Roman Massopust, Dariusz Pawełczak, Zbigniew Pasieka, Łukasz Krakowczyk, Adam Maciejewski
Introduction Colonoscopy trainers have gained recognition for improving endoscopy skills and preparing for real procedures on humans. Unfortunately, due to their high price, commercial simulators are hard to obtain, especially for small medical centers. However, a solution might be to construct a device for themselves. Aim Our goal was to build a relatively cheap and easy-to-construct simulator for residents who want to start learning colonoscopy. Materials and methods The box model colonoscopy trainer was designed and constructed...
October 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28990250/galectin-3-is-persistently-increased-in-early-rheumatoid-arthritis-ra-and-associates-with-anti-ccp-seropositivity-and-mri-bony-lesions-while-early-fibrosis-markers-correlate-with-disease-activity
#7
Saida Farah Issa, Anne Friesgaard Christensen, Hanne M Lindegaard, Merete L Hetland, Kim Hørslev-Petersen, Kristian Stengaard-Pedersen, Bo Jannik Ejbjerg, Tine Lottenburger, Torkell Ellingsen, Jens Kristian Pedersen, Kirsten Junker, Anders Svendsen, Ulrik Tarp, Mikkel Østergaard, Peter Junker
Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic Resonance Imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months...
October 9, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28987594/auxiliary-subunits-of-ampa-receptors-the-discovery-of-a-forebrain-selective-antagonist-ly3130481-cerc-611
#8
REVIEW
Akihiko S Kato, Jeffrey M Witkin
Drugs originate from the discovery of compounds, natural or synthetic, that bind to proteins (receptors, enzymes, transporters, etc.) The interaction of which modulates biological cascades that have potential therapeutic benefit. Rational strategies in identifying novel drug therapies are typically based on knowledge of the structure of the target proteins and the design of new chemical entities that modulate these proteins in a beneficial manner. The present review discusses a novel approach to drug discovery based on the identification and characterization of auxiliary proteins, the transmembrane AMPA receptor regulatory proteins (TARPs) that are associated with AMPA receptors, which led to the discovery of the TARP-dependent-AMPA forebrain selective receptor antagonist (TDAA), LY3130481/CERC-611 that is currently in clinical development for epilepsy...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28963093/effectiveness-of-optional-videoconferencing-based-treatment-of-alcohol-use-disorders-randomized-controlled-trial
#9
Kristine Tarp, Anders Bo Bojesen, Anna Mejldal, Anette Søgaard Nielsen
BACKGROUND: Treatment of alcohol use disorders (AUDs) is characterized by an adherence rate below 50%. Clinical research has found that patient adherence enhances treatment effect; hence, health authorities, clinicians, and researchers strive to explore initiatives contributing to patients receiving treatment. Concurrently, videoconferencing-based treatment is gaining ground within other addiction and psychiatric areas. OBJECTIVE: The aim of this study was to test whether optional videoconferencing increases adherence to and effectiveness of AUD treatment in a randomized controlled trial (RCT)...
September 29, 2017: JMIR Mental Health
https://www.readbyqxmd.com/read/28933963/delayed-sample-arrival-at-the-laboratory-does-not-lead-to-more-false-negatives-in-the-danish-population-screening-for-colorectal-cancer
#10
Anette Tarp Hansen, Elke Hoffmann-Lücke, Betina Klint Nielsen, Birgitte Reinholdt, Peter Hindersson, Karin Heidemann, Nete Hornung
In Denmark, biennial population screening for colorectal cancer was introduced in 2014 for all aged 50-74 years. Five laboratories representative for the regional division of Denmark perform the immunochemical testing of faecal occult blood in the screening samples (iFOBT, OC-Sensor (Eiken Chemical, cut-off 100 µg/L)). In July 2016, a new agreement on the public post-delivery entailed an increased lag time (five days) from the screening participant drops the screening sample into a mail-box until sample arrival at the laboratories...
September 21, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28871958/control-of-ampa-receptor-activity-by-the-extracellular-loops-of-auxiliary-proteins
#11
Irene Riva, Clarissa Eibl, Rudolf Volkmer, Anna L Carbone, Andrew Jr Plested
At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including TARPs. However, how TARPs modulate AMPA receptor gating remains poorly understood. We built structural models of TARP-AMPA receptor complexes for TARPs γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of TARPs. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly...
August 30, 2017: ELife
https://www.readbyqxmd.com/read/28854690/performance-of-the-multitarget-mikrogen-chlamydia-trachomatis-igg-elisa-in-the-prediction-of-tubal-factor-infertility-tfi-in-subfertile-women-comparison-with-the-medac-momp-igg-elisa-plus
#12
Eleanne F van Ess, Sander Ouburg, Joke Spaargaren, Jolande A Land, Servaas A Morré
There is a need for more accurate Chlamydia trachomatis (CT) IgG antibody tests for tubal factor infertility (TFI) diagnostics. We evaluated the predictive value for TFI of Medac ELISA plus (MOMP) and multitarget Mikrogen ELISA (MOMP-CPAF-TARP). Based on Medac ELISA plus results, 183 subfertile women underwent either hysterosalpingography or laparoscopy to diagnose TFI. TFI was defined as extensive adhesions and/or distal occlusion of at least one tube. Women not fulfilling the definition of TFI served as controls...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28825787/structural-determinants-of-the-%C3%AE-8-tarp-dependent-ampa-receptor-antagonist
#13
Matthew R Lee, Kevin M Gardinier, Douglas L Gernert, Douglas A Schober, Rebecca A Wright, He Wang, Yuewei Qian, Jeffrey M Witkin, Eric S Nisenbaum, Akihiko S Kato
The forebrain specific AMPA receptor antagonist, LY3130481/CERC-611, which selectively antagonizes the AMPA receptors associated with TARP γ-8, an auxiliary subunit enriched in the forebrain, has potent antiepileptic activities without motor side effects. We designated the compounds with such activities as γ-8 TARP dependent AMPA receptor antagonists (γ-8 TDAAs). In this work, we further investigated the mechanisms of action using a radio-labeled γ-8 TDAA and ternary structural modeling with mutational validations to characterize the LY3130481 binding to γ-8...
August 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28814579/hepatosplenic-schistosomiasis-playing-hide-and-seek-with-an-elusive-parasite
#14
Martin Baekby, Henning Glerup, Katrine Stribolt, Britta Tarp
A 27-year-old man of Eritrean origin presented with persistent left-sided abdominal pain. Initial investigation showed signs of liver fibrosis, portal hypertension and splenomegaly. A diagnosis of hepatosplenic schistosomiasis was suspected on grounds of elevated total IgE, grey area antischistosomiasis antibodies and the high endemic status of his native country. However, repeated microscopy of faecal and urine samples, as well as rectal biopsies, failed to demonstrate schistosomal eggs. Finally, the diagnosis of hepatosplenic schistosomiasis was established through demonstration of a Schistosoma mansoni egg in a liver biopsy taken in an attempt to clarify the cause of the above findings...
August 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28772007/the-impact-of-comorbidities-on-tumor-necrosis-factor-inhibitor-therapy-in-psoriatic-arthritis-a-population-based-cohort-study
#15
Christine Ballegaard, Pil Højgaard, Lene Dreyer, René Cordtz, Tanja Schjødt Jørgensen, Marie Skougaard, Simon Tarp, Lars Erik Kristensen
OBJECTIVE: The objective of this population-based cohort study was to investigate the impact of comorbidities on disease activity, treatment response and persistence with the first-tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA). METHODS: Data on patient characteristics, disease activity and treatment response and persistence was obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register...
August 3, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28768197/dual-effects-of-tarp-%C3%AE-2-on-glutamate-efficacy-can-account-for-ampa-receptor-autoinactivation
#16
Ian D Coombs, David M MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G Cull-Candy
Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28757050/electroencephalographic-cognitive-and-neurochemical-effects-of-ly3130481-cerc-611-a-selective-antagonist-of-tarp-%C3%AE-8-associated-ampa-receptors
#17
Jeffrey M Witkin, Jennifer Li, Gary Gilmour, Stephen N Mitchell, Guy Carter, Scott D Gleason, Wesley F Seidel, Brian J Eastwood, Andrew McCarthy, Warren J Porter, Jon Reel, Kevin M Gardinier, Akihiko S Kato, Keith A Wafford
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) γ-8. This molecule has been characterized as a potent and efficacious anticonvulsant in an array of acute and chronic epilepsy models in rodents. The present set of experiments was designed to assess the effects of LY3130481 on the electroencephelogram (EEG), cognitive function, and neurochemical outflow...
July 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28749592/porphyrin-antennas-on-carbon-nanodots-excited-state-energy-and-electron-transduction
#18
Francesca Arcudi, Volker Strauss, Luka Đorđević, Alejandro Cadranel, Dirk M Guldi, Maurizio Prato
We report the synthesis and electron donor-acceptor features of a novel nanohybrid, in which the light-harvesting and electron-donating properties of a meso-tetraarylporphyrin (TArP) are combined with the electron-accepting features of nitrogen-doped carbon nanodots (NCNDs). In particular, in an ultrafast process (>10(12)  s(-1) ), visible-light excitation transforms the strongly quenched porphyrin singlet excited states into short-lived (225 ps) charge-separated states. On the other hand, ultraviolet light excitation triggers a non-resolvable transduction of singlet excited state energy from the NCNDs to the porphyrins, followed by the same charge separation observed upon visible light excitation...
July 27, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28609687/off-tarp-emissions-distribution-and-efficacy-of-carbonated-fumigants-in-a-low-permeability-film-tarped-field
#19
Ruijun Qin, Suduan Gao, John E Thomas, Dong Wang, Bradley D Hanson
Carbonated fumigants have been shown to distribute quickly and uniformly in sandy soils and improve pest control efficacy for annual crops. Low permeability films, such as VaporSafe® (TIF), could further improve fumigant dispersion by effectively retaining the fumigant in soil; however, there is a concern that the TIF can lead to higher off-tarp edge emissions. An orchard field trial was conducted to determine the off-tarp emissions, distribution, efficacy, and fate of carbonated Telone® C35 [63.4% 1,3-dichloropropene (1,3-D), 34...
June 10, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28586478/autoregulation-of-rbm10-and-cross-regulation-of-rbm10-rbm5-via-alternative-splicing-coupled-nonsense-mediated-decay
#20
Yue Sun, Yufang Bao, Wenjian Han, Fan Song, Xianfeng Shen, Jiawei Zhao, Ji Zuo, David Saffen, Wei Chen, Zefeng Wang, Xintian You, Yongbo Wang
Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). Through computational analysis and experimental validation, we identified RBM10-promoted skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5 as the underlying AS-NMD events...
August 21, 2017: Nucleic Acids Research
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