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https://www.readbyqxmd.com/read/28316886/identification-of-dysregulated-genes-in-rheumatoid-arthritis-based-on-bioinformatics-analysis
#1
Ruihu Hao, Haiwei Du, Lin Guo, Fengde Tian, Ning An, Tiejun Yang, Changcheng Wang, Bo Wang, Zihao Zhou
BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA. METHODS: The integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein-protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA...
2017: PeerJ
https://www.readbyqxmd.com/read/28298418/disrupting-the-cd47-sirp%C3%AE-anti-phagocytic-axis-by-a-humanized-anti-cd47-antibody-is-an-efficacious-treatment-for-malignant-pediatric-brain-tumors
#2
Sharareh Gholamin, Siddhartha S Mitra, Abdullah H Feroze, Jie Liu, Suzana A Kahn, Michael Zhang, Rogelio Esparza, Chase Richard, Vijay Ramaswamy, Marc Remke, Anne K Volkmer, Stephen Willingham, Anitha Ponnuswami, Aaron McCarty, Patricia Lovelace, Theresa A Storm, Simone Schubert, Gregor Hutter, Cyndhavi Narayanan, Pauline Chu, Eric H Raabe, Griffith Harsh, Michael D Taylor, Michelle Monje, Yoon-Jae Cho, Ravi Majeti, Jens P Volkmer, Paul G Fisher, Gerald Grant, Gary K Steinberg, Hannes Vogel, Michael Edwards, Irving L Weissman, Samuel H Cheshier
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28295628/pathophysiological-aspects-of-red-blood-cells-in-end-stage-renal-disease-patients-resistant-to-recombinant-human-erythropoietin-therapy
#3
Hara T Georgatzakou, Vassilis L Tzounakas, Anastasios G Kriebardis, Athanassios D Velentzas, Effie G Papageorgiou, Artemis I Voulgaridou, Apostolos C Kokkalis, Marianna H Antonelou, Issidora S Papassideri
OBJECTIVE: Modified, bio-reactive red blood cells (RBCs) and RBC-derived microvesicles likely contribute to the hematological and cardiovascular complications in end-stage renal disease (ESRD). This study assesses the physiological profile of red blood cells (RBCs) in end-stage renal disease (ESRD) patients receiving standard or high doses of recombinant human erythropoietin (rhEPO). METHOD: Blood samples from twenty-eight patients under sustained hemodialysis, responsive or not to standard rhEPO administration were examined for RBC morphology, fragility, hemolysis, redox status, removal signaling, membrane protein composition and microvesiculation before and after dialysis...
March 10, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28289091/membrane-nanoclusters-of-fc%C3%AE-ri-segregate-from-inhibitory-sirp%C3%AE-upon-activation-of-human-macrophages
#4
Filipa B Lopes, Štefan Bálint, Salvatore Valvo, James H Felce, Edith M Hessel, Michael L Dustin, Daniel M Davis
Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton...
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28286874/investigation-of-the-adaptor-protein-plic-2-in-multiple-pathways
#5
Khiem Nguyen, Robbins Puthenveetil, Olga Vinogradova
PLIC, Protein Linking IAP (CD47) to Cytoskeleton, have long since been implicated in connecting the extracellular membrane to the intracellular cell cytoskeleton. This phenomenon is supposedly achieved by bridging a receptor protein CD47 to vimentin, an intermediate filament, which in turn regulates integrin dependent cell spreading. Since the discovery of these proteins, the molecular details of the above-mentioned interactions and the underlying complexes are yet to be characterized. Several independent studies have together emphasized PLIC/Ubiquilin's role in the proteasomal degradation pathway...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#6
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28275508/targeting-cd47-the-achievements-and-concerns-of-current-studies-on-cancer-immunotherapy
#7
COMMENT
Yuting Huang, Yuchi Ma, Peng Gao, Zhi Yao
Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction...
February 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#8
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28268219/treg-cells-protect-dopaminergic-neurons-against-mpp-neurotoxicity-via-cd47-sirpa-interaction
#9
Yan Huang, Zhan Liu, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
BACKGROUND/AIMS: Regulatory T (Treg) cells have been associated with neuroprotection by inhibiting microglial activation in animal models of Parkinson's disease (PD), a progressive neurodegenerative disease characterized by dopaminergic neuronal loss in the nigrostriatal system. Herein, we show that Treg cells directly protect dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity via an interaction between the two transmembrane proteins CD47 and signal regulatory protein α (SIRPA)...
March 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28258703/the-cd47-sirp%C3%AE-signaling-axis-as-an-innate-immune-checkpoint-in-cancer
#10
REVIEW
Hanke L Matlung, Katka Szilagyi, Neil A Barclay, Timo K van den Berg
Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell-mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer. This innate immune checkpoint is composed of what has become known as the 'don't-eat me' signal CD47, which is a protein broadly expressed on normal cells and often overexpressed on cancer cells, and its counter-receptor, the myeloid inhibitory immunoreceptor SIRPα...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28228282/complement-factor-h-inhibits-cd47-mediated-resolution-of-inflammation
#11
Bertrand Calippe, Sebastien Augustin, Fanny Beguier, Hugo Charles-Messance, Lucie Poupel, Jean-Baptiste Conart, Shulong J Hu, Sophie Lavalette, Alexandre Fauvet, Julie Rayes, Olivier Levy, William Raoul, Catherine Fitting, Thomas Denèfle, Matthew C Pickering, Claire Harris, Sylvie Jorieux, Patrick M Sullivan, José-Alain Sahel, Philippe Karoyan, Przemyslaw Sapieha, Xavier Guillonneau, Emmanuel L Gautier, Florian Sennlaub
Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28220078/inhibition-of-vegfr2-activation-and-its-downstream-signaling-to-erk1-2-and-calcium-by-thrombospondin-1-tsp1-in-silico-investigation
#12
Hojjat Bazzazi, Jeffery S Isenberg, Aleksander S Popel
VEGF signaling through VEGFR2 is a central regulator of the angiogenic response. Inhibition of VEGF signaling by the stress-induced matricellular protein TSP1 plays a role in modulating the angiogenic response to VEGF in both health and disease. TSP1 binding to CD47 inhibits VEGFR2 activation. The full implications of this inhibitory interaction are unknown. We developed a detailed rule-based computational model to inquire if TSP1-CD47 signaling through VEGF had downstream effects upon ERK1/2 and calcium. Our Simulations suggest that enhanced degradation of VEGFR2 initiated by the binding of TSP1 to CD47 is sufficient to explain the inhibition of VEGFR2 phosphorylation, calcium elevation, and ERK1/2 activation downstream of VEGF...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28208074/cd47-limits-antibody-dependent-phagocytosis-against-non-malignant-b-cells
#13
Sandra Gallagher, Sean Turman, Kristen Lekstrom, Susan Wilson, Ronald Herbst, Yue Wang
Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28186432/development-of-anti-cd47-single-chain-variable-fragment-targeted-magnetic-nanoparticles-for-treatment-of-human-bladder-cancer
#14
Gashin Rezaei, Mahdi Habibi-Anbouhi, Morteza Mahmoudi, Kayhan Azadmanesh, Shima Moradi-Kalbolandi, Mahdi Behdani, Leila Ghazizadeh, Mohsen Abolhassani, Mohammad Ali Shokrgozar
AIM: To develop a novel anti-CD47 single-chain variable fragment (scFv) functionalized magnetic nanoparticles (MNPs) for targeting bladder cell lines and its applicability in thermotherapy. MATERIAL & METHODS: An immunized murine antibody phage display library was constructed and screened to isolate anti-CD47 binders. A scFv was selected and conjugated to MNPs which was then utilized to discriminate CD47(+) bladder cells along with assessing its efficacy in thermotherapy...
February 10, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28161480/multifunctionalized-iron-oxide-nanoparticles-for-selective-targeting-of-pancreatic-cancer-cells
#15
Sara Trabulo, Antonio Aires, Alexandra Aicher, Christopher Heeschen, Aitziber L Cortajarena
Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28153099/selective-blockade-of-the-ubiquitous-checkpoint-receptor-cd47-is-enabled-by-dual-targeting-bispecific-antibodies
#16
Elie Dheilly, Valéry Moine, Lucile Broyer, Susana Salgado-Pires, Zoë Johnson, Anne Papaioannou, Laura Cons, Sébastien Calloud, Stefano Majocchi, Robert Nelson, François Rousseau, Walter Ferlin, Marie Kosco-Vilbois, Nicolas Fischer, Krzysztof Masternak
CD47 is a ubiquitously expressed immune checkpoint receptor that is often upregulated in cancer. CD47 interacts with its counter-receptor SIRPα on macrophages and other myeloid cells to inhibit cancer cell phagocytosis and drive immune evasion. To overcome tolerability and "antigen sink" issues arising from widespread CD47 expression, we generated dual-targeting bispecific antibodies that selectively block the CD47-SIRPα interaction on malignant cells expressing a specific tumor-associated antigen; e.g., CD19 or mesothelin...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28148733/dynamic-interaction-and-phospho-proteomics-reveal-lck-as-a-major-signaling-hub-of-cd147-in-t-cells
#17
Verena Supper, Ingrid Hartl, Cyril Boulègue, Anna Ohradanova-Repic, Hannes Stockinger
Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28134664/the-walking-dead-macrophage-inflammation-and-death-in-atherosclerosis
#18
Mary M Kavurma, Katey J Rayner, Denuja Karunakaran
PURPOSE OF REVIEW: To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis. RECENT FINDINGS: Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque...
January 27, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#19
Hayato Iwase, Hong Liu, Eva Schmelzer, Mohamed Ezzelarab, Martin Wijkstrom, Hidetaka Hara, Whayoung Lee, Jagjit Singh, Cassandra Long, Eric Lagasse, Jörg C Gerlach, David K C Cooper, Bruno Gridelli
BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28100392/replication-study-the-cd47-signal-regulatory-protein-alpha-sirpa-interaction-is-a-therapeutic-target-for-human-solid-tumors
#20
Stephen K Horrigan
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors "(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al...
January 19, 2017: ELife
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