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https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#1
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28727817/immunogenicity-of-a-novel-clade-b-hiv-1-vaccine-combination-results-of-phase-1-randomized-placebo-controlled-trial-of-an-hiv-1-gm-csf-expressing-dna-prime-with-a-modified-vaccinia-ankara-vaccine-boost-in-healthy-hiv-1-uninfected-adults
#2
Susan P Buchbinder, Nicole A Grunenberg, Brittany J Sanchez, Kelly E Seaton, Guido Ferrari, M Anthony Moody, Nicole Frahm, David C Montefiori, Christine M Hay, Paul A Goepfert, Lindsey R Baden, Harriet L Robinson, Xuesong Yu, Peter B Gilbert, M Juliana McElrath, Yunda Huang, Georgia D Tomaras
BACKGROUND: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. METHODS: Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28724967/a-balancing-act-rna-binding-protein-hur-ttp-axis-in-endometriosis-patients
#3
Kasra Khalaj, Soo Hyun Ahn, Mallikarjun Bidarimath, Yasmin Nasirzadeh, Sukhbir S Singh, Asgerally T Fazleabas, Steven L Young, Bruce A Lessey, Madhuri Koti, Chandrakant Tayade
Endometriosis, a major reproductive pathology affecting 8-10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722316/the-mincle-ligand-trehalose-dibehenate-differentially-modulates-m1-like-and-m2-like-macrophage-phenotype-and-function-via-syk-signaling
#4
Kristel Kodar, Jacquie L Harper, Melanie J McConnell, Mattie S M Timmer, Bridget L Stocker
INTRODUCTION: Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied. METHODS: qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle(-/-) mice...
July 19, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28721202/defining-the-inflammatory-signature-of-human-lung-explant-tissue-in-the-presence-and-absence-of-glucocorticoid
#5
Tracy L Rimington, Emily Hodge, Charlotte K Billington, Sangita Bhaker, Binaya K C, Iain Kilty, Scott Jelinsky, Ian P Hall, Ian Sayers
BACKGROUND:  Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. METHOD:  Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM)...
2017: F1000Research
https://www.readbyqxmd.com/read/28720900/low-frequency-ultrasound-induced-vegf-suppression-and-synergy-with-dendritic-cell-mediated-anti-tumor-immunity-in-murine-prostate-cancer-cells-in-vitro
#6
Wei Zhang, Wen-De Shou, Yan-Jun Xu, Wen-Kun Bai, Bing Hu
High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720441/increased-tnf-alpha-and-stnfr2-levels-are-associated-with-high-grade-anal-squamous-intraepithelial-lesions-in-hiv-positive-patients-with-low-cd4-level
#7
Takeshi Haga, Jimmy T Efird, Sharof Tugizov, Joel M Palefsky
Compared with HIV-negative individuals, HIV-positive individuals have a higher prevalence of anogenital human papillomavirus (HPV) infection, the causative agent of anogenital cancer. TNF-alpha is a major proinflammatory cytokine. sTNFR2 is the soluble form of one of its receptors and is strongly expressed on stimulated lymphocytes. To further understand the role of TNF-alpha, sTNFR2 and other cytokines in the pathogenesis in HPV-related neoplasia, the profiles of serum cytokines in high-risk patients were analyzed for association with anal lesion status...
June 2017: Papillomavirus Research
https://www.readbyqxmd.com/read/28716883/role-of-the-%C3%AE-common-%C3%AE-c-family-of-cytokines-in-health-and-disease
#8
Timothy R Hercus, Winnie L T Kan, Sophie E Broughton, Denis Tvorogov, Hayley S Ramshaw, Jarrod J Sandow, Tracy L Nero, Urmi Dhagat, Emma J Thompson, Karen S Cheung Tung Shing, Duncan R McKenzie, Nicholas J Wilson, Catherine M Owczarek, Gino Vairo, Andrew D Nash, Vinay Tergaonkar, Timothy Hughes, Paul G Ekert, Michael S Samuel, Claudine S Bonder, Michele A Grimbaldeston, Michael W Parker, Angel F Lopez
The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28714105/spinal-cord-imaging-using-averaged-magnetization-inversion-recovery-acquisitions
#9
Matthias Weigel, Oliver Bieri
PURPOSE: To establish a novel approach for fast high-resolution spinal cord (SC) imaging using averaged magnetization inversion recovery acquisitions (AMIRA). METHODS: The AMIRA concept is based on an inversion recovery (IR) prepared, segmented, and time-limited cine balanced steady state free precession sequence. Typically, for the fastest SC imaging without any signal averaging, eight consecutive images in time with an in-plane resolution of 0.67 × 0.67 mm(2) and 6 mm to 8 mm slice thickness are acquired in 51 s...
July 16, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28712033/oncolytic-immunotherapy-unlocking-the-potential-of-viruses-to-help-target-cancer
#10
REVIEW
Omid Hamid, Brianna Hoffner, Eduard Gasal, Jenny Hong, Richard D Carvajal
Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF)...
July 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28705941/tyk2-as-a-target-for-immune-regulation-in-human-viral-bacterial-pneumonia
#11
Johanna Berg, Katja Zscheppang, Diana Fatykhova, Mario Tönnies, Torsten T Bauer, Paul Schneider, Jens Neudecker, Jens C Rückert, Stephan Eggeling, Maria Schimek, Achim D Gruber, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke
The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lung ex vivo co-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.We revealed that type I and III interferon (IFN) inhibits Streptococcus pneumoniae-induced interleukin (IL)-1β release...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28699816/enrichment-of-ly6c-hi-monocytes-by-multiple-gm-csf-injections-with-hbv-vaccine-contributes-to-viral-clearance-in-a-hbv-mouse-model
#12
Weidong Zhao, Xian Zhou, Gan Zhao, Qing Lin, Xianzheng Wang, Xueping Yu, Bin Wang
Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential of the combination in AAV8-1...
July 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28698014/adenoviral-expressed-recombinant-granulocyte-monocyte-colony-stimulating-factor-gm-csf-enhances-protective-immunity-induced-by-inactivated-newcastle-disease-virus-ndv-vaccine
#13
Xinglong Wang, Xiangwei Wang, Yanqing Jia, Chongyang Wang, Qinqsong Han, Zen H Lu, Zengqi Yang
Although vaccination has been hugely successful in protecting birds against infection by the New castle disease virus (NDV), newly-emerged highly virulent strains have been found to overcome established immune protection and threaten the poultry industry. The need to improve the immunization efficacy is, therefore, urgent. Here, we tested the potential immunostimulatory adjuvant activity of the adenoviral-expressed recombinant chicken granulocyte monocyte colony stimulating factor (rchGM-CSF) in an inactivated Newcastle Disease Virus (NDV) vaccine...
July 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28694696/th17-profile-in-copd-exacerbations
#14
REVIEW
Marco Antonio Ponce-Gallegos, Alejandra Ramírez-Venegas, Ramcés Falfán-Valencia
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow. It is mainly associated with exposure to cigarette smoke. In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide. Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28694526/intrapatient-functional-clonality-deconvoluted-by-coupling-intracellular-flow-cytometry-and-next-generation-sequencing-in-human-leukemia
#15
Q Zhang, M C Ball, Y Zhao, M Balasis, C Letson, A Vedder, A F List, P K Epling-Burnette, R S Komrokji, E Padron
The interplay between tumor heterogeneity and microenvironmental factors is a critical mechanism for clonal selection in leukemia. Evidence of unique clonal capacities to engraft within patient-derived xenograft (PDX) models suggests that intrapatient genetic architecture may be defined by functional differences at the clonal level. However, methods to detect functional differences assigned to genetically defined clones remain limited. Here, we describe a scalable method to directly measure the functional properties of clones within the same leukemia patient by coupling intracellular flow cytometry and next-generation sequencing (NGS)...
June 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28689771/immunosuppression-with-tacrolimus-improved-implantation-and-rescued-expression-of-uterine-progesterone-receptor-and-its-co-regulators-fkbp52-and-piasy-at-nidation-in-the-obese-and-diabetic-mice-comparative-studies-with-metformin
#16
Ahmad J H Albaghdadi, Frederick W K Kan
Diabesity is often associated with subfertility and recurrent miscarriages. Evidence links systemic and local uterine cytotoxicity to the pathogenesis of implantation failure (IF) in diabetes. Immunosuppression with tacrolimus improved pregnancy outcomes in obese and diabetic mice and repeated IF in women with elevated Th1/Th2 blood cell ratios. However the mode of action of tacrolimus in protecting against IF and the molecular mechanisms associated with recurrent miscarriages in the obese and diabetic subjects are yet to be elucidated...
July 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28689166/ocular-surface-cytokine-profile-in-chronic-stevens-johnson-syndrome-and-its-response-to-mucous-membrane-grafting-for-lid-margin-keratinisation
#17
Srividya Gurumurthy, Geetha Iyer, Bhaskar Srinivasan, Shweta Agarwal, Narayanasamy Angayarkanni
BACKGROUND: To study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK). METHODS: In a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer's strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17)...
July 8, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28683563/modulation-of-hematopoietic-lineage-specification-impacts-trem2-expression-in-microglia-like-cells-derived-from-human-stem-cells
#18
Peter J Amos, Susan Fung, Amanda Case, Jerusalem Kifelew, Leah Osnis, Carole L Smith, Kevin Green, Alipi Naydenov, Macarena Aloi, Jesse J Hubbard, Aravind Ramakrishnan, Gwenn A Garden, Suman Jayadev
Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28682305/ifn-%C3%AE-promotes-transendothelial-migration-of-cd4-t-cells-across-the-blood-brain-barrier
#19
Sandip Ashok Sonar, Shagufta Shaikh, Nupura Joshi, Ashwini N Atre, Girdhari Lal
Transendothelial migration (TEM) of Th1 and Th17 cells across the blood-brain barrier (BBB) plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE). How cytokines produced by inflammatory Th1 and Th17 cells damage the endothelial BBB and promote transendothelial migration of immune cells into the central nervous system (CNS) during autoimmunity is not understood. We therefore investigated the effect of various cytokines on brain endothelial cells. Among the various cytokines tested, such as Th1 (IFN-γ, IL-1α, IL-1β, TNF-α, IL-12), Th2 (IL-3, IL-4, IL-6 and IL-13), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23, GM-CSF) and Treg-specific cytokines (IL-10 and TGF-β), IFN-γ predominantly showed increased expression of ICAM-1, VCAM-1, MAdCAM-1, H2-K(b) and I-A(b) molecules on brain endothelial cells...
July 6, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28679643/endogenous-heat-shock-protein-induction-with-or-without-radiofrequency-ablation-or-cryoablation-in-patients-with-stage-iv-melanoma
#20
Evidio Domingo-Musibay, James M Heun, Wendy K Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A Erickson, Svetomir N Markovic
LESSONS LEARNED: Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen. BACKGROUND: Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs)...
July 5, 2017: Oncologist
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