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https://www.readbyqxmd.com/read/29444453/efferocytosis-in-atherosclerotic-lesions-malfunctioning-regulatory-pathways-and-control-mechanisms
#1
REVIEW
Amir Tajbakhsh, Mehdi Rezaee, Petri T Kovanen, Amirhossein Sahebkar
Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process...
February 11, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29429992/srsf10-mediated-il1rap-alternative-splicing-regulates-cervical-cancer-oncogenesis-via-mil1rap-nf-%C3%AE%C2%BAb-cd47-axis
#2
Fei Liu, Miao Dai, Qinyang Xu, Xiaolu Zhu, Yang Zhou, Shuheng Jiang, Yahui Wang, Zhihong Ai, Li Ma, Yanli Zhang, Lipeng Hu, Qin Yang, Jun Li, Shujie Zhao, Zhigang Zhang, Yincheng Teng
High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an "accomplice" of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation...
February 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29425774/a-membrane-type-surfactant-protein-d-sp-d-suppresses-macrophage-mediated-cytotoxicity-in-swine-endothelial-cells
#3
Patmika Jiaravuthisan, Akira Maeda, Chihiro Takakura, Han-Tang Wang, Rieko Sakai, Afifah Mohd Shabri, Pei-Chi Lo, Rei Matsuura, Tasuku Kodama, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
OBJECTIVE: Surfactant protein D (SP-D), which is secreted mainly in the lung, is an oligometric C type lectin that promotes phagocytosis by binding to carbohydrates on microbial surfaces. SP-D can also bind SIRPα, leading to a decrease in cytokine production by monocytes/macrophages. In the present study, we examined the possibility that SP-D suppresses macrophage-mediated xenogeneic cytotoxicity, by creating a membrane-type SP-D. METHODS: The cDNA for the carbohydrate recognition domain (CRD) of human SP-D was switched to that of a membrane-type protein, collectin placenta 1 (CL-P1), with a Flag-tag...
February 6, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29416769/roles-of-malat1-in-development-and-migration-of-triple-negative-and-her-2-positive-breast-cancer
#4
Zhang Xiping, Chen Bo, Yang Shifeng, Yu Feijiang, Yang Hongjian, Cheng Qihui, Tang Binbin
Background: As a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported. Objectives: In this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416092/cd63-mhc-class-1-and-cd47-identify-subsets-of-extracellular-vesicles-containing-distinct-populations-of-noncoding-rnas
#5
Sukhbir Kaur, Abdel G Elkahloun, Anush Arakelyan, Lynn Young, Timothy G Myers, Francisco Otaizo-Carrasquero, Weiwei Wu, Leonid Margolis, David D Roberts
Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies...
February 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29414673/evolving-targets-for-the-treatment-of-atherosclerosis
#6
REVIEW
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29399202/characterization-of-cluster-of-differentiation-47-expression-and-its-potential-as-a-therapeutic-target-in-esophageal-squamous-cell-cancer
#7
Chun-Lin Zhao, Shuang Yu, Shu-Hui Wang, Shi-Gang Li, Zhi-Ju Wang, Sheng-Na Han
The increased expression of cluster of differentiation (CD)47 has been identified in a number of different tumor types and is recognized as an adverse prognostic factor that indicates an increased risk of mortality in patients. The binding of CD47 to signal regulatory protein α (SIRPα) inhibits the macrophage phagocytosis of tumor cells by triggering an inhibitory 'do not eat me' signal. This is one of the mechanisms used by tumor cells to evade immune surveillance. In the present study, CD47 levels and macrophage infiltration were assessed in patients with esophageal squamous cell cancer (ESCC)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29367423/chemotherapy-induces-enrichment-of-cd47-cd73-pdl1-immune-evasive-triple-negative-breast-cancer-cells
#8
Debangshu Samanta, Youngrok Park, Xuhao Ni, Huili Li, Cynthia A Zahnow, Edward Gabrielson, Fan Pan, Gregg L Semenza
Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and is often characterized by early relapse and metastasis. To form a secondary (recurrent and/or metastatic) tumor, a breast cancer cell must evade the innate and adaptive immune systems. CD47 enables cancer cells to evade killing by macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein expression, leading to a marked increase in the percentage of CD47+CD73+PDL1+ breast cancer cells...
January 24, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338788/high-throughput-immunophenotypic-characterization-of-bone-marrow-and-cord-blood-derived-mesenchymal-stromal-cells-reveals-common-and-differentially-expressed-markers-identification-of-angiotensin-converting-enzyme-cd143-as-a-marker-differentially-expressed
#9
Eliana Amati, Omar Perbellini, Gianluca Rotta, Martina Bernardi, Katia Chieregato, Sabrina Sella, Francesco Rodeghiero, Marco Ruggeri, Giuseppe Astori
BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking...
January 16, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29336991/sirp%C3%AE-cd47-immune-checkpoint-blockade-in-anticancer-therapy
#10
REVIEW
André Veillette, Jun Chen
Inhibitory immune checkpoint blockade has been one of the most significant advances in anticancer therapy of the past decade. Research so far has largely focused on improving adaptive immune functions, but recent studies have indicated that the signal-regulatory protein (SIRP)α-CD47 pathway, a phagocytosis checkpoint in macrophages and other innate immune cells, may be an interesting therapeutic target. Here, we summarize current knowledge about SIRPα-CD47 blockade, and highlight key issues for future investigations...
January 11, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29321087/cd47-promotes-human-glioblastoma-invasion-through-activation-of-pi3k-akt-pathway
#11
Xuejian Liu, Xia Wu, Yanming Wang, Yuhua Li, Xiangli Chen, Wenchuan Yang, Lihua Jiang
Excessive expression of Cluster of Differentiation 47 (CD47) is common in various malignancies. The aim of this study was to investigate whether CD47 promotes human glioblastoma invasion and its underlying mechanism of CD47 in promoting glioblastoma invasion. In this study we found that CD47 expression was stronger in glioblastoma patients and cells in comparison with normal controls. CD47 downregulation modulated by siRNA suppressed invasion in vitro. However, excessive CD47 expression modulated by transfection exerted opposite influence...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29308321/blocking-the-cd47-sirp%C3%AE-axis-by-delivery-of-anti-cd47-antibody-induces-antitumor-effects-in-glioma-and-glioma-stem-cells
#12
Feng Li, Bingke Lv, Yang Liu, Tian Hua, Jianbang Han, Chengmei Sun, Limin Xu, Zhongfei Zhang, Zhiming Feng, Yingqian Cai, Yuxi Zou, Yiquan Ke, Xiaodan Jiang
Tumor initiating cells or cancer stem cells (CSCs) play an important role in the initiation, development, metastasis, and recurrence of tumors. However, traditional therapies have limited effects against CSCs and targeting these cells is crucial when developing new therapeutic strategies against cancer. One potentially targetable factor is CD47, a member of the immunoglobulin superfamily. This protein acts as an anti-phagocytic "don't eat me" signal and is often found expressed by cancer cells, particularly CSCs...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308308/cd20-selective-inhibition-of-cd47-sirp%C3%AE-don-t-eat-me-signaling-with-a-bispecific-antibody-derivative-enhances-the-anticancer-activity-of-daratumumab-alemtuzumab-and-obinutuzumab
#13
Peter E van Bommel, Yuan He, Ilona Schepel, Mark A J M Hendriks, Valerie R Wiersma, Robert J van Ginkel, Tom van Meerten, Emanuele Ammatuna, Gerwin Huls, Douwe F Samplonius, Wijnand Helfrich, Edwin Bremer
Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα "don't eat me" signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20pos/CD47pos malignant B-cells, but not of CD20neg/CD47pos cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer antibodies daratumumab (anti-CD38), alemtuzumab (anti-CD52) and obinutuzumab (anti-CD20)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29296731/human-and-murine-splenic-neutrophils-are-potent-phagocytes-of-igg-opsonized-red-blood-cells
#14
Sanne M Meinderts, Per-Arne Oldenborg, Boukje M Beuger, Thomas R L Klei, Johanna Johansson, Taco W Kuijpers, Takashi Matozaki, Elise J Huisman, Masja de Haas, Timo K van den Berg, Robin van Bruggen
Red blood cell (RBC) clearance is known to occur primarily in the spleen, and is presumed to be executed by red pulp macrophages. Erythrophagocytosis in the spleen takes place as part of the homeostatic turnover of RBCs to remove old RBCs. It can be strongly promoted by immunoglobulin G (IgG) opsonization of RBCs, a condition that can occur as a consequence of autoantibody or alloantibody formation. The purpose of our study was to investigate which phagocytes are involved in IgG-mediated RBC clearance in the human spleen...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288236/cd47-blockade-as-an-adjuvant-immunotherapy-for-resectable-pancreatic-cancer
#15
Alex D Michaels, Timothy E Newhook, Sara J Adair, Sho Morioka, Bernadette J Goudreau, Sarbajeet Nagdas, Matthew G Mullen, Jesse B Persily, Timothy Bullock, Craig L Slingluff, Kodi S Ravichandran, J Thomas Parsons, Todd W Bauer
PURPOSE: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and adjuvant chemotherapy have an expected survival of only two years due to disease recurrence, frequently in the liver. We investigated the role of liver macrophages in progression of PDAC micrometastases to identify adjuvant treatment strategies that could prolong survival. EXPERIMENTAL DESIGN: A murine splenic injection model of hepatic micrometastatic PDAC was used with five patient-derived PDAC tumors...
December 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29287252/paraquat-treatment-modulates-integrin-associated-protein-cd47-and-basigin-cd147-expression-and-mitochondrial-potential-on-erythroid-cells-in-mice
#16
Nitin Bhardwaj, Ashutosh Singh
The present study is focused on the interaction of paraquat with the erythroid system in bone marrow and spleen of mice. Administration of paraquat (10 mg/kg of body weight i.p. on alternate days in C57Bl/6 mice) induced the level of reactive oxygen species in bone marrow (BM) on 7, 14, and 21 day time points but it was unchanged in spleen erythroid cell. A marked induction of CD147 expression in BM and spleen erythroid cells was observed in the paraquat treated mice. Paraquat treatment also modulated the CD47 expression in erythroid cells and its expression level was significantly higher on day 14, 21 and 28 in bone marrow and on day 14 and 21 in spleen...
December 23, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29214179/the-roles-of-thrombospondins-in-hemorrhagic-stroke
#17
REVIEW
Xuan Wu, Xu Luo, Qiquan Zhu, Jie Zhang, Yun Liu, Hansheng Luo, Yuan Cheng, Zongyi Xie
Hemorrhagic stroke is a devastating cerebrovascular disease with significant morbidity and mortality worldwide. Thrombospondins (TSPs), as matricellular proteins, belong to the TSP family which is comprised of five members. All TSPs modulate a variety of cellular functions by binding to various receptors. Recently, TSPs gained attention in the area of hemorrhagic stroke, especially TSP-1. TSP-1 participates in angiogenesis, the inflammatory response, apoptosis, and fibrosis after hemorrhagic stroke through binding to various molecules including but not limited to CD36, CD47, and TGF-β...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29213290/effect-of-isolation-technique-and-location-on-the-phenotype-of-human-corneal-stroma-derived-cells
#18
Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Morten C Moe, Goran Petrovski
Purpose: To determine the effect of the isolation technique and location upon the phenotype of human corneal stroma-derived cells (CSCs). Methods: CSCs were isolated from the corneal stroma center and periphery using the explant or enzymatic digestion technique. The native tissue was stained for functional markers, while cultured cells were analysed by FACS. PCR was used to determine gene expression in the cultured versus native cells. Results: The native stroma was positive for α-actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29203952/effect-of-intra-tumoral-magnetic-nanoparticle-hyperthermia-and-viral-nanoparticle-immunogenicity-on-primary-and-metastatic-cancer
#19
P Jack Hoopes, Courtney M Mazur, Bjorn Osterberg, Ailin Song, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Steven N Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia...
January 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/29203951/hypo-fractionated-radiation-magnetic-nanoparticle-hyperthermia-and-a-viral-immunotherapy-treatment-of-spontaneous-canine-cancer
#20
P Jack Hoopes, Karen L Moodie, Alicia A Petryk, James D Petryk, Shawntel Sechrist, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Ashish Rajan, Danielle Dugat, Margaret Crary-Burney, Steven N Fiering
It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component...
January 2017: Proceedings of SPIE
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