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https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#1
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#2
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909794/prescription-of-oral-antidiabetic-drugs-in-tyrol-data-from-the-tyrol-diabetes-registry-2012-2015
#3
Lukas Lunger, Andreas Melmer, Willi Oberaigner, Marco Leo, Martin Juchum, Karin Pölzl, Johannes Gänzer, Martha Innerebner, Egon Eisendle, Gertrud Beck, Hermann Kathrein, Bernhard Heindl, Hans Robert Schönherr, Monika Lechleitner, Herbert Tilg, Christoph Ebenbichler
Diabetes mellitus affects 9% of the adult population worldwide and the economic burden of the disease is growing exponentially. In type 2 diabetes mellitus (T2DM), when life style interventions fail to achieve treatment targets, oral antidiabetic drugs are prescribed to improve glycemic control. Several new oral antidiabetics have been launched in the last few years, which enlarged the spectrum of available treatment options in T2DM. The present study aimed to examine T2DM treatment patterns in a cohort of 7769 patients recruited from the Diabetes Registry Tyrol (DRT) with at least one visit from 2012-2015...
December 1, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27909740/clinical-pharmacokinetics-of-magnesium-sulfate-in-the-treatment-of-children-with-severe-acute-asthma
#4
Joseph E Rower, Xiaoxi Liu, Tian Yu, Michael Mundorff, Catherine M T Sherwin, Michael D Johnson
PURPOSE: Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS: To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospective data from 54 children who received IV MgSO4 for treatment of an acute asthma exacerbation at Primary Children's Hospital in Salt Lake City, UT...
December 2, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27908829/exploring-the-binding-mechanism-of-heteroaryldihydropyrimidines-and-hepatitis-b-virus-capsid-combined-3d-qsar-and-molecular-dynamics
#5
Jing Tu, Jiao Jiao Li, Zhi Jie Shan, Hong Lin Zhai
The non-nucleoside drugs have been developed to treat HBV infection owing to their increased efficacy and lesser side effects, in which heteroaryldihydropyrimidines (HAPs) have been identified as effective inhibitors of HBV capsid. In this paper, the binding mechanism of HAPs targeting on HBV capsid protein was explored through three-dimensional quantitative structure-activity relationship, molecular dynamics and binding free energy decompositions. The obtained models of comparative molecular field analysis and comparative molecular similarity indices analysis enable the sufficient interpretation of structure-activity relationship of HAPs-HBV...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908581/sonodynamic-inactivation-of-gram-positive-and-gram-negative-bacteria-using-a-rose-bengal-antimicrobial-peptide-conjugate
#6
David Costley, Heather Nesbitt, Nigel Ternan, James Dooley, Ying-Ying Huang, Michael R Hamblin, Anthony P McHale, John F Callan
Combating antimicrobial resistance is one of the most serious public health challenges facing society today. The development of new antibiotics or alternative techniques that can help combat antimicrobial resistance is being prioritised by many governments and stakeholders across the globe. Antimicrobial photodynamic therapy is one such technique that has received considerable attention but is limited by the inability of light to penetrate through human tissue, reducing its effectiveness when used to treat deep-seated infections...
November 17, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27906748/evolving-therapies-for-hepatitis-c-virus-in-chronic-kidney-disease-the-beginning-of-a-new-era
#7
Craig E Gordon, Claudia Nader
PURPOSE OF REVIEW: The current review highlights recent advances in treatment of chronic hepatitis C virus infection using new classes of agents, direct-acting antivirals (DAAs), with a focus on the evidence for their use in the setting of chronic kidney disease (CKD) stages 4-5, hemodialysis, and kidney transplantation. RECENT FINDINGS: DAA agents target-specific proteins involved in the hepatitis C virus life cycle and interrupt viral replication. Sustained virologic response, a marker of viral eradication, occurs in more than 90% of patients treated with DAA agents in the general population...
November 30, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27905186/severe-asthma-current-management-targeted-therapies-and-future-directions-a-roundtable-report
#8
REVIEW
Vanessa M McDonald, Steven Maltby, Helen K Reddel, Gregory G King, Peter A B Wark, Lorraine Smith, John W Upham, Alan L James, Guy B Marks, Peter G Gibson
Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1-5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5-10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden...
November 30, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27903285/prognostic-biomarkers-to-identify-patients-destined-to-develop-severe-crohn-s-disease-who-may-benefit-from-early-biological-therapy-protocol-for-a-systematic-review-meta-analysis-and-external-validation
#9
Steve Halligan, Darren Boone, Gauraang Bhatnagar, Tariq Ahmad, Stuart Bloom, Manuel Rodriguez-Justo, Stuart A Taylor, Susan Mallett
BACKGROUND: It is believed increasingly that patients with severe Crohn's disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. However, we cannot predict currently which new presentations of Crohn's disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Accordingly, via systematic review and meta-analysis we aim to identify if biomarkers of disease activity are able to predict development of severe disease...
December 1, 2016: Systematic Reviews
https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#10
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#11
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27903197/upfront-boost-gamma-knife-leading-edge-radiosurgery-to-flair-mri-defined-tumor-migration-pathways-in-174-patients-with-glioblastoma-multiforme-a-15-year-assessment-of-a-novel-therapy
#12
Christopher M Duma, Brian S Kim, Peter V Chen, Marianne E Plunkett, Ralph Mackintosh, Marlon S Mathews, Ryan M Casserly, Gustavo A Mendez, Daniel J Furman, Garrett Smith, Nathan Oh, Chad A Caraway, Ami R Sanathara, Robert O Dillman, Azzurra-Sky Riley, David Weiland, Lian Stemler, Ruslana Cannell, Daniela Alexandru Abrams, Alexa Smith, Christopher M Owen, Burton Eisenberg, Michael Brant-Zawadzki
OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27902995/systemic-lupus-erythematosus-a-review-of-the-clinical-approach-to-diagnosis-and-update-on-current-targeted-therapies
#13
Joanne Szczygiel Cunha, Katarzyna Gilek-Seibert
Systemic lupus erythematosus (SLE) is a chronic, complicated and challenging disease to diagnose and treat. The etiology of SLE is unknown, but certain risk factors have been identified that lead to immune system dysfunction with antibody formation and immune complex deposition. This immune system dysregulation causes organ injury, contributing to the variable manifestations and relapsing-remitting course of the disease. Criteria were created to aide in the diagnosis, focusing on clinical manifestations and antibody profiles specific to SLE...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27902617/efficacy-of-bosentan-in-patients-with-refractory-thromboangiitis-obliterans-buerger-disease-a-case-series-and-review-of-the-literature
#14
Javier Narváez, Carmen García-Gómez, Lorenzo Álvarez, Pilar Santo, María Aparicio, María Pascual, Mercè López de Recalde, Helena Borrell, Joan M Nolla
The cornerstone of therapy in thromboangiitis obliterans (TAO) is complete abstinence from tobacco. In addition to discontinuation of cigarette smoking, very few pharmacological and surgical options of controversial efficacy are available to date. New therapeutic options with greater efficacy are clearly needed to properly manage these patients.In this preliminary study, we assessed the effectiveness and safety of bosentan in a case series of 8 adults with TAO and severe ischemic ulceronecrotic lesions who were treated with bosentan after inadequate response to platelet inhibitors, vasodilators, and intravenous alprostadil...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#15
Yunyu Chen, Jing Zhang, Dongsheng Li, Jiandong Jiang, Yanchang Wang, Shuyi Si
Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902447/a-unique-type-of-gsk-3-inhibitor-brings-new-opportunities-to-the-clinic
#16
Avital Licht-Murava, Rom Paz, Lilach Vaks, Limor Avrahami, Batya Plotkin, Miriam Eisenstein, Hagit Eldar-Finkelman
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimer's disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27902445/focus-issue-new-horizons-for-treating-neurological-disease
#17
EDITORIAL
Leslie K Ferrarelli
This issue of Science Signaling highlights research that uncovers protein interaction networks and potential drug targets, as well as research that identifies molecular mechanisms of action of novel or existing drugs, for neurological and psychological disease. This Editorial Guide features a handful of papers from 2016 that join the ranks of Science Signaling's vast archive of articles related to neuroscience.
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27900350/swath-ms-dataset-of-heat-shock-treated-drosophila-melanogaster-embryos
#18
Bertrand Fabre, Dagmara Korona, Daniel J H Nightingale, Steven Russell, Kathryn S Lilley
Data independent acquisition (DIA) has emerged as a promising mass spectrometry based approach, combining the advantages of shotgun and targeted proteomics. Here we applied a DIA approach (termed SWATH) to monitor the dynamics of the Drosophila melanogaster embryonic proteome upon heat-shock treatment. Embryos were incubated for 0.5, 1 or 3 h at 37 °C to induce heat-shock or maintained at 25 °C. The present dataset contains SWATH files acquired on a Sciex Triple-TOF 6600. A spectral library built in-house was used to analyse these data and led to the quantification of more than 2500 proteins at every timepoint...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27899881/transcriptomics-of-environmental-enrichment-reveals-a-role-for-retinoic-acid-signaling-in-addiction
#19
Yafang Zhang, Fanping Kong, Elizabeth J Crofton, Steven N Dragosljvich, Mala Sinha, Dingge Li, Xiuzhen Fan, Shyny Koshy, Jonathan D Hommel, Heidi M Spratt, Bruce A Luxon, Thomas A Green
There exists much variability in susceptibility/resilience to addiction in humans. The environmental enrichment paradigm is a rat model of resilience to addiction-like behavior, and understanding the molecular mechanisms underlying this protective phenotype may lead to novel targets for pharmacotherapeutics to treat cocaine addiction. We investigated the differential regulation of transcript levels using RNA sequencing of the rat nucleus accumbens after environmental enrichment/isolation and cocaine/saline self-administration...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27898745/-internet-based-opportunities-in-breast-cancer-diagnostics-and-research
#20
Ádám Nagy, Balázs Gyõrffy
A new generation of internet-based diagnostic and research tools have arrived in the last decade. The most extensive group of these includes programs predicting the expected survival mainly by utilizing clinical data of the patient. This includes Adjuvant! Online, the MSKCC and MD Anderson nomograms and the UK-based PREDICT algorithm. A common feature of all these is the comparison of the given patient to previously treated breast cancer samples, and evaluating the clinical outcome of these previous patients...
November 29, 2016: Magyar Onkologia
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