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https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#1
Jun Chen, Ming-Chao Zhong, Huaijian Guo, Dominique Davidson, Sabrin Mishel, Yan Lu, Inmoo Rhee, Luis-Alberto Pérez-Quintero, Shaohua Zhang, Mario-Ernesto Cruz-Munoz, Ning Wu, Donald C Vinh, Meenal Sinha, Virginie Calderon, Clifford A Lowell, Jayne S Danska, André Veillette
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424250/unifying-mechanism-for-different-fibrotic-diseases
#2
Gerlinde Wernig, Shih-Yu Chen, Lu Cui, Camille Van Neste, Jonathan M Tsai, Neeraja Kambham, Hannes Vogel, Yaso Natkunam, D Gary Gilliland, Garry Nolan, Irving L Weissman
Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts...
April 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28403150/pedf-increases-the-tumoricidal-activity-of-macrophages-towards-prostate-cancer-cells-in-vitro
#3
Dalia Martinez-Marin, Courtney Jarvis, Thomas Nelius, Werner de Riese, Olga V Volpert, Stéphanie Filleur
BACKGROUND: Although inflammation and prostate cancer (PCa) have been linked, the molecular interactions between macrophages and PCa cells are poorly explored. Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor factor. We previously showed that PEDF induces macrophages recruitment in vitro, correlates with macrophages density in human prostate, and stimulates macrophages polarization towards the classically activated pathway. Here, we demonstrate that PEDF modulates the interaction between macrophages and PCa cells through a bidirectional signalling leading to tumor cell apoptosis and phagocytosis...
2017: PloS One
https://www.readbyqxmd.com/read/28398662/rhesus-ce-expression-on-patient-red-blood-cells-is-an-independent-prognostic-factor-for-adenocarcinoma-of-the-lung
#4
A B Schulze, L H Schmidt, L Baie, B Heitkötter, A Kümmel, M Mohr, R Buhl, H Hillmann, G Geißler, R Kelsch, D Görlich, W E Berdel, W Hartmann, R Wiewrodt
OBJECTIVES: The influence of blood group antigens on cancerogenesis is shown for distinct tumor types, yet the impact of Rhesus blood group antigens in lung cancer is not clarified. MATERIALS AND METHODS: To investigate the impact of Rhesus blood groups a non-small cell lung cancer (NSCLC) collective (n=1,047) was analyzed retrospectively. Using a second cohort of n=340 primarily operated stage I-III NSCLC patients, we evaluated immunohistochemistry of CD47-antibody stained tissue samples in correlation to histopathologic subtype and Rhesus blood group...
April 11, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28393401/the-potentiating-effect-of-htfpi-in-the-presence-of-hcd47-reduces-the-cytotoxicity-of-human-macrophages
#5
Sung Han Jung, Jeong Ho Hwang, Sang Eun Kim, Kim Young Kyu, Hyo Chang Park, Hoon Taek Lee
BACKGROUND: In pig-to-human xenotransplantation, hyperacute rejection of pig organs could be overcome by the production of α1,3-galactosyltransferase knockout pigs. However, macrophage-mediated acute rejection is another obstacle that needs to be overcome. Among the various candidate genes involved in acute rejection, CD47 inhibits monocyte/macrophage-mediated phagocytosis by identifying the CD47 signal regulatory protein alpha (SIRP-α) as self/non-self. Tissue factor pathway inhibitor (TFPI) is involved in the regulation of the coagulation pathway and is able to bind to another ligand of CD47, thrombospondin-1 (TSP-1)...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28383780/immunoglobulin-superfamily-members-encoded-by-viruses-and-their-multiple-roles-in-immune-evasion
#6
REVIEW
Domènec Farré, Pablo Martínez-Vicente, Pablo Engel, Ana Angulo
Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily (IgSF), whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28380460/cd47-promotes-ovarian-cancer-progression-by-inhibiting-macrophage-phagocytosis
#7
Ran Liu, Huiting Wei, Peng Gao, Hu Yu, Ke Wang, Zheng Fu, Baohui Ju, Meng Zhao, Shangwen Dong, Zhijun Li, Yifeng He, Yuting Huang, Zhi Yao
Targeting CD47 efficiently enhances macrophage phagocytosis in both physiological and pathological conditions. Anti-CD47 antibodies have been shown to inhibit the progression of several types of cancer. However, the mechanism of anti-CD47 monoclonal antibody (mAb) treatment remains controversial. In this study, we confirmed that CD47 protein is highly expressed in ovarian cancer, and is correlated with poor clinical characteristics and prognosis. CD47 knockdown in the ovarian cancer cell line, SK-OV-3, promoted phagocytosis by macrophages in vitro and inhibited tumor growth in vivo...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28378740/a-cd47-associated-super-enhancer-links-pro-inflammatory-signalling-to-cd47-upregulation-in-breast-cancer
#8
Paola A Betancur, Brian J Abraham, Ying Y Yiu, Stephen B Willingham, Farnaz Khameneh, Mark Zarnegar, Angera H Kuo, Kelly McKenna, Yoko Kojima, Nicholas J Leeper, Po Ho, Phung Gip, Tomek Swigut, Richard I Sherwood, Michael F Clarke, George Somlo, Richard A Young, Irving L Weissman
CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels by neoplastic and normal cells. Here, to reveal mechanisms by which different neoplastic cells generate this dominant 'don't eat me' signal, we analyse the CD47 regulatory genomic landscape. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression...
April 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28365151/a-cell-surface-membrane-protein-signature-for-glioblastoma
#9
Dhimankrishna Ghosh, Cory C Funk, Juan Caballero, Nameeta Shah, Katherine Rouleau, John C Earls, Liliana Soroceanu, Greg Foltz, Charles S Cobbs, Nathan D Price, Leroy Hood
We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2...
March 28, 2017: Cell Systems
https://www.readbyqxmd.com/read/28361932/neuro-oncology-cd47-antibody-helps-phagocytes-fight-paediatric-cancer
#10
Charlotte Ridler
No abstract text is available yet for this article.
March 31, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28356441/left-ventricular-dysfunction-switches-mesenchymal-stromal-cells-toward-an-inflammatory-phenotype-and-impairs-their-reparative-properties-via-toll-like-receptor-4
#11
Nili Naftali-Shani, La-Paz Levin-Kotler, Dahlia Palevski, Uri Amit, David Kain, Natalie Landa, Edith Hochhauser, Jonathan Leor
Background -Little is known about the potentially unfavorable effects of mesenchymal stromal cell (MSC) activation on the heart. MSCs can respond to tissue injury by anti or pro-inflammatory activation. We sought to study the potential negative interaction between left ventricular dysfunction (LVD) and MSC activation. Methods -We isolated MSCs from cardiac (c) and subcutaneous (sc) fat tissues of mice with LVD, 28 days after myocardial infarction (MI), or sham operation. To evaluate the effect of LVD on MSCs, we characterized cMSCs and scMSCs in vitro Subsequently, we injected MSCs or saline into the infarcted myocardium of mice and evaluated left ventricular (LV) remodeling, and function, 28 days after MI...
March 29, 2017: Circulation
https://www.readbyqxmd.com/read/28351890/targeting-cd47-and-autophagy-elicited-enhanced-antitumor-effects-in-non-small-cell-lung-cancer
#12
Xuyao Zhang, Jiajun Fan, Shaofei Wang, Yubin Li, Yichen Wang, Song Li, Jingyun Luan, Ziyu Wang, Ping Song, Qicheng Chen, Wenzhi Tian, Dianwen Ju
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in NSCLC. SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28341665/an-anti-cd47-antibody-is-effective-in-pediatric-brain-tumor-models
#13
(no author information available yet)
The anti-CD47 antibody Hu5F9-G4 selectively kills tumor cells in pediatric brain tumor PDX models.
March 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28337964/targeting-cd47-enhances-the-efficacy-of-anti-pd-1-and-ctla-4-in-esophageal-squamous-cell-cancer-preclinical-model
#14
Hua Tao, Pudong Qian, Feijiang Wang, Hongliang Yu, Yesong Guo
Esophageal squamous cell cancer is a highly aggressive cancer with dismal five-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presenting of the immune system. Via interacting with signal regulatory protein-alpha expressed in antigen presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APCs dependent antigen presenting. Overxpression of CD47 was found in various cancer types. However, its role in esophageal squamous cell cancer is not clear yet...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28316886/identification-of-dysregulated-genes-in-rheumatoid-arthritis-based-on-bioinformatics-analysis
#15
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
#16
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
#17
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
#18
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...
April 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28286874/investigation-of-the-adaptor-protein-plic-2-in-multiple-pathways
#19
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
#20
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
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