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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28097229/anti-sirp%C3%AE-antibodies-as-a-potential-new-tool-for-cancer-immunotherapy
#10
Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei-Ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per-Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki
Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28087905/-inflammatory-cytokines-and-oxidative-stress-markers-in-the-inhibition-of-osteoarthritis-by-curcumin
#11
Jun Liu, Xiaole He, Ping Zhen, Shenghu Zhou, Xusheng Li
Objective: To observe the influence of matrix metalloproteinases-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), CD47, L-selectin and advanced oxidation proteinproducts (AOPP) in osteoarthritis and the intervention of curcumin. Methods: A total of 20 male C57BL/6 mice (10.05-15.00 g) were randomly divided into control group, OA group, Cur25 group and Cur50 group (intraperitoneal injected 25 μmol/L or 50 μmol/L of curcumin everyday after modeling). After 4 weeks treatment, we observed the morphological changes of the gross specimen by immunohistochemical method, and observed the ultrastructure of cartilage tissue under electron microscope...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077173/is-cd47-an-innate-immune-checkpoint-for-tumor-evasion
#12
REVIEW
Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang-Xin Fu
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28076333/surgical-debulking-promotes-recruitment-of-macrophages-and-triggers-glioblastoma-phagocytosis-in-combination-with-cd47-blocking-immunotherapy
#13
Huaiyang Zhu, Lina Leiss, Ning Yang, Cecilie B Rygh, Siddhartha S Mitra, Samuel H Cheshier, Irving L Weissman, Bin Huang, Hrvoje Miletic, Rolf Bjerkvig, Per Ø Enger, Xingang Li, Jian Wang
Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking in preclinical models. Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. Orthotopic patient-derived xenograft tumors expressing CD47 were resected at 4 weeks after implantation and immediately thereafter treated with anti-CD47 or control antibodies injected into the cavity...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069696/what-mediates-the-effects-of-thrombospondin-1-in-pulmonary-hypertension-new-evidence-for-a-dual-pronged-role-of-cd47
#14
EDITORIAL
Wolfgang M Kuebler
No abstract text is available yet for this article.
January 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28065241/expressions-of-cd44-cd47-and-c-met-in-ovarian-clear-cell-carcinoma-and-their-clinical-significance
#15
Hui-Min Wang, Ming-Zi Tan, Song Zhang, Xiao Li, Jian Gao, Dan-Ye Zhang, Ying-Ying Hao, Song Gao, Juan-Juan Liu, Bei Lin
Objective To investigate the expressions of CD44,CD47,and c-met in ovarian clear cell carcinoma (OCCC) tissue and their correlations with clinical variables and prognosis. Methods Immunohistochemical method was used to investigate the expressions of CD44,CD47,and c-met in tissues from 86 OCCC patients and the relationships of their expressions with the clinicopathological factors of OCCC were analyzed. Results The expressions of CD44,CD47,and c-met were significantly high in OCCC tissues (90.7%,91.9%,and 94...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28061465/sirp%C3%AE-antibody-fusion-proteins-stimulate-phagocytosis-and-promote-elimination-of-acute-myeloid-leukemia-cells
#16
Laia Pascual Ponce, Nadja C Fenn, Nadine Moritz, Christina Krupka, Jan-Hendrik Kozik, Kirsten Lauber, Marion Subklewe, Karl-Peter Hopfner
CD47, expressed on a variety of tumor cells, confers immune resistance by delivering an inhibitory "don't eat me" signal to phagocytic cells via its myeloid-specific receptor SIRPα. Recent studies have shown that blocking the CD47-SIRPα axis with CD47-directed antibodies or antibody-derivatives enhances phagocytosis and increases antitumor immune effects. However, CD47 expression on healthy cells creates an antigen sink and potential sites of toxicity, limiting the efficacy of CD47-directed therapies. In this study, we first characterized CD47 expression in Acute Myeloid Leukemia (AML) patients (n = 213) and found that CD47 is highly expressed on both AML bulk and stem cells irrespective of the disease state...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28033649/thrombospondin-derived-peptide-attenuates-sj%C3%A3-gren-s-syndrome-associated-ocular-surface-inflammation-in-mice
#17
Laura Contreras Ruiz, Fayaz A Mir, Bruce Turpie, Sharmila Masli
Sjögren's syndrome is a second most common rheumatic disease in which autoimmune response targets exocrine glands (salivary and lacrimal glands) resulting in clinical symptoms of dry mouth and dry eye. Inflammation of the lacrimal gland induces tear abnormalities that contribute to the inflammation of the ocular surface, which includes ocular mucosa. Thrombospondin-1 (TSP-1) plays a critical regulatory role in the ocular mucosa and as such TSP-1-/- mice spontaneously develop chronic ocular surface inflammation associated with Sjögren's syndrome (SS)...
December 29, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28032398/cultivation-and-characterisation-of-the-surface-markers-and-carbohydrate-profile-of-human-corneal-endothelial-cells
#18
Richárd Nagymihály, Zoltán Veréb, Réka Albert, Laura Sidney, Harminder Dua, Andrew Hopkinson, Goran Petrovski
BACKGROUND: To characterise human corneal endothelial cell (HCEnC) cultures generated by the peel-and-digest method based on their surface protein/carbohydrate expression pattern. METHODS: QPCR was used to compare expression of Vimentin, CD90, Cytokeratin-19, ZO-1, Claudin 14 in cultured HCEnC and cell line B4G12 versus stromal cells. Fluorescence-activated cell sorting (FACS) was used to assess surface protein distribution of cultured and uncultured HCEnC. Distribution of surface proteins/ carbohydrates was visualised by immunofluorescent and lectin staining...
December 29, 2016: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/28019031/pathogen-inactivation-by-riboflavin-and-ultraviolet-light-illumination-accelerates-the-red-blood-cell-storage-lesion-and-promotes-eryptosis
#19
Syed M Qadri, Deborah Chen, Peter Schubert, Darian L Perruzza, Varsha Bhakta, Dana V Devine, William P Sheffield
BACKGROUND: Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life...
December 26, 2016: Transfusion
https://www.readbyqxmd.com/read/27965383/defects-in-cd4-t-cell-lfa-1-integrin-dependent-adhesion-and-proliferation-protect-cd47-mice-from-eae
#20
Veronica Azcutia, Ribal Bassil, Jan M Herter, Daniel Engelbertsen, Gail Newton, Anu Autio, Tanya Mayadas, Andrew H Lichtman, Samia J Khoury, Charles A Parkos, Wassim Elyaman, Francis W Luscinskas
CD47 is known to play an important role in CD4(+) T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47(-/-)) CD4(+) T cell adhesion and transendothelial migration (TEM) in vivo and in vitro as a result of impaired expression of high-affinity forms of LFA-1 and VLA-4 integrins. A prior study concluded that Cd47(-/-) mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4(+) T cell activation after myelin oligodendrocyte glycoprotein peptide 35-55 aa (MOG35-55) immunization...
December 13, 2016: Journal of Leukocyte Biology
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