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https://www.readbyqxmd.com/read/28522599/engineering-macrophages-to-eat-cancer-from-marker-of-self-cd47-and-phagocytosis-to-differentiation
#1
REVIEW
Cory Alvey, Dennis E Discher
The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28484605/how-do-red-blood-cells-know-when-to-die
#2
Clemente Fernandez Arias, Cristina Fernandez Arias
Human red blood cells (RBCs) are normally phagocytized by macrophages of splenic and hepatic sinusoids at 120 days of age. The destruction of RBCs is ultimately controlled by antagonist effects of phosphatidylserine (PS) and CD47 on the phagocytic activity of macrophages. In this work, we introduce a conceptual model that explains RBC lifespan as a consequence of the dynamics of these molecules. Specifically, we suggest that PS and CD47 define a molecular algorithm that sets the timing of RBC phagocytosis. We show that significant changes in RBC lifespan described in the literature can be explained as alternative outcomes of this algorithm when it is executed in different conditions of oxygen availability...
April 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28484448/anti-cd47-antibody-as-a-targeted-therapeutic-agent-for-human-lung-cancer-and-cancer-stem-cells
#3
Liang Liu, Lin Zhang, Lin Yang, Hui Li, Runmei Li, Jinpu Yu, Lili Yang, Feng Wei, Cihui Yan, Qian Sun, Hua Zhao, Fan Yang, Hao Jin, Jian Wang, Shizhen Emily Wang, Xiubao Ren
Accumulating evidence indicates that a small subset of cancer cells, termed the tumor-initiating cells or cancer stem cells (CSCs), construct a reservoir of self-sustaining cancer cells with the characteristic ability to self-renew and maintain the tumor mass. The CSCs play an important role in the tumor initiation, development, relapse, metastasis, and the ineffectiveness of conventional cancer therapies. CD47 is a ligand for signal-regulatory protein-α expressed on phagocytic cells and functions to inhibit phagocytosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28465453/rational-combination-immunotherapy-understand-the-biology
#4
Howard L Kaufman
Selecting rational treatment combinations remains a major challenge for improving immunotherapy outcomes. In this issue of Cancer Immunology Research, Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway. By also targeting autophagy, the therapeutic response improved, highlighting the importance of understanding the biology beneath antitumor immunity. Cancer Immunol Res; 5(5); 355-6. ©2017 AACRSee article by Zhang et al...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28455393/sirp%C3%AE-cd47-blockade-mediated-tumor-cell-phagocytosis-requires-slamf7
#5
(no author information available yet)
SLAMF7 expression is required for macrophage-mediated phagocytosis of hematopoietic tumor cells.
April 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#6
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#7
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 27, 2017: Nature
https://www.readbyqxmd.com/read/28424250/unifying-mechanism-for-different-fibrotic-diseases
#8
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...
May 2, 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
#9
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
#10
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
#11
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
#12
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, 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...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28380460/cd47-promotes-ovarian-cancer-progression-by-inhibiting-macrophage-phagocytosis
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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 non-small cell lung cancer (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, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28341665/an-anti-cd47-antibody-is-effective-in-pediatric-brain-tumor-models
#19
(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
#20
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
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