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Acute phase response

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https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#1
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#2
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910163/serum-amyloid-a-an-acute-phase-protein-stimulates-proliferative-and-proinflammatory-responses-of-keratinocytes
#3
Ning Yu, Shujie Zhang, Jiajing Lu, Ying Li, Xuemei Yi, Li Tang, Lina Su, Yangfeng Ding
OBJECTIVES: Serum amyloid A (SAA), an acute phase protein, is highly expressed in psoriatic lesions but its function is not fully understood. The aim of this study was to explore its role in activation of keratinocytes. MATERIALS AND METHODS: Real-time PCR and immunofluorescence were performed to examine SAA expression in imiquimod (IMQ)-induced psoriasis-like mice. In vivo function of SAA was examined by treating psoriasis-like mice with SAA neutralising antibody...
December 2, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27909401/implicit-learning-in-transient-global-amnesia-and-the-role-of-stress
#4
Frauke Nees, Martin Griebe, Anne Ebert, Michaela Ruttorf, Benjamin Gerber, Oliver T Wolf, Lothar R Schad, Achim Gass, Kristina Szabo
Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning-the latter defined as learning and memory processes that lack conscious awareness of the information acquired...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27909037/safety-and-efficacy-of-stereotactic-body-radiation-therapy-combined-with-s-1-simultaneously-followed-by-sequential-s-1-as-an-initial-treatment-for-locally-advanced-pancreatic-cancer-silapanc-trial-study-design-and-rationale-of-a-phase-ii-clinical-trial
#5
Xiaofei Zhu, Xiaoping Ju, Fei Cao, Fang Fang, Shuiwang Qing, Yuxin Shen, Zhen Jia, Yangsen Cao, Huojun Zhang
INTRODUCTION: Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine...
December 1, 2016: BMJ Open
https://www.readbyqxmd.com/read/27907040/the-role-of-reactive-oxygen-species-in-%C3%AE-adrenergic-signaling-in-cardiomyocytes-from-mice-with-the-metabolic-syndrome
#6
Monica Llano-Diez, Jon Sinclair, Takashi Yamada, Mei Zong, Jeremy Fauconnier, Shi-Jin Zhang, Abram Katz, Kent Jardemark, Håkan Westerblad, Daniel C Andersson, Johanna T Lanner
The metabolic syndrome is associated with prolonged stress and hyperactivity of the sympathetic nervous system and afflicted subjects are prone to develop cardiovascular disease. Under normal conditions, the cardiomyocyte response to acute β-adrenergic stimulation partly depends on increased production of reactive oxygen species (ROS). Here we investigated the interplay between beta-adrenergic signaling, ROS and cardiac contractility using freshly isolated cardiomyocytes and whole hearts from two mouse models with the metabolic syndrome (high-fat diet and ob/ob mice)...
2016: PloS One
https://www.readbyqxmd.com/read/27906023/surface-area-dependence-of-gas-particle-interactions-influences-pulmonary-and-neuroinflammatory-outcomes
#7
Christina R Tyler, Katherine E Zychowski, Bethany N Sanchez, Valeria Rivero, Selita Lucas, Guy Herbert, June Liu, Hammad Irshad, Jacob D McDonald, Barry E Bleske, Matthew J Campen
BACKGROUND: Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE(-/-)) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G...
December 1, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27905678/a-phase-i-ii-trial-of-at9283-a-selective-inhibitor-of-aurora-kinase-in-children-with-relapsed-or-refractory-acute-leukemia-challenges-to-run-early-phase-clinical-trials-for-children-with-leukemia
#8
B Vormoor, G J Veal, M J Griffin, A V Boddy, J Irving, L Minto, M Case, U Banerji, K E Swales, J R Tall, A S Moore, M Toguchi, G Acton, K Dyer, C Schwab, C J Harrison, J D Grainger, D Lancaster, P Kearns, D Hargrave, J Vormoor
Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27903234/acute-phase-proteins-and-their-potential-role-as-an-indicator-for-fish-health-and-in-diagnosis-of-fish-diseases
#9
Suvra Roy, Vikash Kumar, Vikas Kumar, B K Behera
The acute phase proteins are biochemically and functionally unrelated protein predominantly synthesized in the liver. The local inflammatory cells i.e. macrophages and neutrophils secretes various cytokines like IL-1, IL-6, IL-8 (interleukins) and TNF-α into bloodstream in response to injury and tissue damage, which stimulate hepatocytes to produce protein and release them into the circulation; these proteins are called as acute phase protein (e.g. C-reactive protein (CRP), serum amyloid A (SAA), metal binding protein, lysozyme, lectin, etc...
November 21, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27903079/preclinical-evaluation-of-a-replication-deficient-recombinant-adenovirus-serotype-5-vaccine-expressing-guanylate-cyclase-c-and-the-padre-t-helper-epitope
#10
Adam Eugene Snook, Trevor R Baybutt, Terry Hyslop, Scott Arthur Waldman
There is an unmet need for improved therapeutics for colorectal cancer, the second leading cause of cancer mortality worldwide. Adjuvant chemotherapy only marginally improves survival in some patients, and has no benefit in others, underscoring the clinical opportunity for novel immunotherapeutic approaches to improve survival in colorectal cancer. In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity...
November 30, 2016: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/27902386/establishment-of-memory-cd8-t-cells-with-live-attenuated-influenza-virus-laiv-across-different-vaccination-doses
#11
Zhongfang Wang, Lukasz Kedzierska, Simone Nuessing, Brendon Chua, Sergio M Quiñones-Parra, Victor C Huber, David Jackson, Paul G Thomas, Katherine Kedzierska
FluMist has been used in children and adults for more than ten years. As pre-existing CD8+ T-cell memory pools can provide heterologous immunity against distinct influenza viruses, it is important to understand influenza-specific CD8+ T-cell responses elicited by different LAIV regimens. In this study, we immunized mice intranasally (i.n.) with two different doses of live-attenuated PR8 virus (PR8 ts, H1N1), low and high, and then assessed protective efficacy by challenging animals with heterosubtypic X31-H3N2 virus at 6 weeks post-vaccination...
November 2, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902344/pre-infection-transcript-levels-of-fam26f-in-pbmcs-inform-about-overall-plasma-viral-load-in-acute-and-postacute-phase-after-siv-infection
#12
Aneela Javed, Nicole Leuchte, Gabriela Salinas, Lennart Opitz, Christiane Stahl-Hennig, Sieghart Sopper, Ulrike Sauermann
CD8+ cells from simian immunodeficiency virus (SIV)-infected long-term non-progressors and some uninfected macaques can suppress viral replication in vitro without killing the infected cells. The aim of the study was to identify factors responsible for non-cytolytic viral suppression by transcriptional profiling and to investigate their potential impact on SIV-replication. Results of microarray experiments and further validation with cells from infected and uninfected macaques revealed that FAM26F RNA levels distinguished CD8+ cells of controllers and non-controllers (p=0...
October 18, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901071/staphylococcus-aureus-dependent-septic-arthritis-in-murine-knee-joints-local-immune-response-and-beneficial-effects-of-vaccination
#13
Alessia Corrado, Paolo Donato, Silvia Maccari, Raffaella Cecchi, Tiziana Spadafina, Letizia Arcidiacono, Simona Tavarini, Chiara Sammicheli, Donatello Laera, Andrea Guido Oreste Manetti, Paolo Ruggiero, Bruno Galletti, Sandra Nuti, Ennio De Gregorio, Sylvie Bertholet, Anja Seubert, Fabio Bagnoli, Giuliano Bensi, Emiliano Chiarot
Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900416/-intensive-care-treatment-after-aneurysmal-subarachnoid-hemorrhage
#14
U Jaschinski
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease and nearly one third of patients die in the acute phase. Due to the bleeding event, a hyperactive sympathetic nervous system and an uncontrolled inflammatory response have a profound local and systemic impact on other organ functions. Neuroendocrinological disorders and cardiopulmonary morbidity are dominant. Despite a decrease in hospital mortality for high volume centers, a high proportion of survivors suffer from neurological deficits. Knowledge of the pathophysiology of vasospasms in the later stages of the disease has increased...
November 29, 2016: Der Anaesthesist
https://www.readbyqxmd.com/read/27900411/inflammatory-protein-response-in-cdkl5-rett-syndrome-evidence-of-a-subclinical-smouldering-inflammation
#15
Alessio Cortelazzo, Claudio de Felice, Silvia Leoncini, Cinzia Signorini, Roberto Guerranti, Roberto Leoncini, Alessandro Armini, Luca Bini, Lucia Ciccoli, Joussef Hayek
BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. METHODS: Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry...
November 29, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27899888/neurophysiological-characterization-of-subacute-stroke-patients-a-longitudinal-study
#16
Giuseppe Lamola, Chiara Fanciullacci, Giada Sgherri, Federica Bertolucci, Alessandro Panarese, Silvestro Micera, Bruno Rossi, Carmelo Chisari
Various degrees of neural reorganization may occur in affected and unaffected hemispheres in the early phase after stroke and several months later. Recent literature suggests to apply a stratification based on lesion location and to consider patients with cortico-subcortical and subcortical strokes separately: different lesion location may also influence therapeutic response. In this study we used a longitudinal approach to perform TMS assessment (Motor Evoked Potentials, MEP, and Silent Period, SP) and clinical evaluations (Barthel Index, Fugl-Meyer Assessment for upper limb motor function and Wolf Motor Function Test) in 10 cortical-subcortical and 10 subcortical ischemic stroke patients...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27898956/effect-of-timing-of-challenge-following-short-term-natural-exposure-to-bovine-viral-diarrhea-virus-type-1b-on-animal-performance-and-immune-response-in-beef-steers
#17
L Carlos-Valdez, B K Wilson, L O Burciaga-Robles, D L Step, B P Holland, C J Richards, M A Montelongo, A W Confer, R W Fulton, C R Krehbiel
Bovine respiratory disease (BRD) is the most common and economically detrimental disease of beef cattle during the postweaning period, causing the majority of morbidity and mortality in feedlots. The pathogenesis of this disease often includes an initial viral infection, which can predispose cattle to a secondary bacterial infection. The objective of this experiment was to determine the effects of timing of an intratracheal (MH) challenge relative to 72 h of natural exposure to bovine viral diarrhea virus (BVDV) type 1b persistently infected (PI) calves on performance, serum antibody production, total and differential white blood cell (WBC) count, rectal temperature, clinical severity score (CS), and haptoglobin (Hp)...
November 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27898011/update-on-inflammatory-biomarkers-and-treatments-in-ischemic-stroke
#18
REVIEW
Aldo Bonaventura, Luca Liberale, Alessandra Vecchié, Matteo Casula, Federico Carbone, Franco Dallegri, Fabrizio Montecucco
After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#19
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896542/immunomodulatory-effects-of-adjuvants-cpg-mpla-and-bcg-on-the-derp2-induced-acute-asthma-at-early-life-in-an-animal-model-of-balb-c-mice
#20
V Mohammadi-Shahrokhi, A Rezaei, A Andalib, A Rahnama, A Jafarzadeh, N Eskandari
The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37...
November 28, 2016: Inflammation
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