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ADAM17 antibodies

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https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#1
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#2
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28675418/the-soluble-interleukin-6-receptor-advanced-therapeutic-options-in-inflammation
#3
REVIEW
Stefan Rose-John
Interleukin (IL)-6 binds to IL-6R and the complex of IL-6 and IL-6R associates with the receptor subunit gp130, which initiates signaling. gp130 is expressed on all cells. IL-6R is cleaved by the ADAM17, generating a soluble IL-6R (sIL-6R). The sIL-6R binds IL-6 and the complex of IL-6 and sIL-6R binds to gp130 even on cells that do not express IL-6R. This process, which has been called IL-6 trans-signaling, increases the spectrum of target cells for IL-6. We generated a protein, sgp130Fc, which inhibits IL-6 trans-signaling without affecting IL-6 classic signaling...
October 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28570994/targeting-adam17-inhibits-human-colorectal-adenocarcinoma-progression-and-tumor-initiating-cell-frequency
#4
Joseph Dosch, Elizabeth Ziemke, Shanshan Wan, Kathryn Luker, Theodore Welling, Karin Hardiman, Eric Fearon, Suneetha Thomas, Matthew Flynn, Jonathan Rios-Doria, Robert Hollingsworth, Ronald Herbst, Elaine Hurt, Judith Sebolt-Leopold
ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFα converting enzyme) has emerged as a potential therapeutic target in colorectal cancer (CRC) and other cancers, due in part to its role in regulating various tumor cell surface proteins and growth factors and cytokines in the tumor microenvironment. The emergence of MEDI3622, a highly potent and specific antibody-based ADAM17 inhibitor, has allowed testing of the concept that targeting ADAM17 may be an important new therapeutic approach for CRC patients...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554668/anti-tumor-effects-of-a-human-mouse-cross-reactive-anti-adam17-antibody-in-a-pancreatic-cancer-model-in-vivo
#5
Jie Ye, Shun Ming Yuen, Gillian Murphy, Ruiyu Xie, Hang Fai Kwok
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumor amongst all human cancers due to late diagnosis and resistant to treatment with chemotherapy and radiation. Preclinical and clinical studies have revealed that ErbB family for example epidermal growth factor receptor (EGFR) is a validated molecular target for pancreatic cancer prevention and therapy. The ErbB signaling cascade is regulated by a member of the ADAM (a disintegrin and metalloprotease) family, namely ADAM17, by enzymatic cleavage of precursor ligands into soluble cytokines and growth factors...
May 26, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28387913/nivolumab-effectively-inhibit-platinum-resistant-ovarian-cancer-cells-via-induction-of-cell-apoptosis-and-inhibition-of-adam17-expression
#6
L-M Sun, Y-C Liu, W Li, S Liu, H-X Liu, L-W Li, R Ma
OBJECTIVE: Nivolumab is an anti-PD-1 (anti-programmed death-1) monoclonal antibody. It has achieved an overall response rate of 17% in Phase 1 clinical trial for patient with platinum-resistant ovarian cancer (PROC). However, its underlying mechanism has not been fully explored yet. The aim of the study is to investigate the efficiency of nivolumab to inhibit PROC cells and its possible mechanism. MATERIALS AND METHODS: Firstly, methylthiazolyl tetrazolium bromide (MTT) assay was performed to determine the IC50 values of cisplatin in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28351660/tweak-fn14-activation-contributes-to-the-pathogenesis-of-bullous-pemphigoid
#7
Yale Liu, Lingling Peng, Liang Li, Chengfei Liu, Xiao Hu, Shengxiang Xiao, Yumin Xia
TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients...
July 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28274635/identification-of-novel-tace-inhibitors-compatible-with-topical-application
#8
Gilles Ouvry, Yaël Berton, Yushma Bhurruth-Alcor, Laetitia Bonnary, Claire Bouix-Peter, Karine Bouquet, Marilyne Bourotte, Sandrine Chambon, Catherine Comino, Benoît Deprez, Denis Duvert, Gwenaëlle Duvert, Feriel Hacini-Rachinel, Craig S Harris, Anne-Pascale Luzy, Arnaud Mathieu, Corinne Millois, Jonathan Pascau, Artur Pinto, Gaëlle Polge, Arnaud Reitz, Kevin Reversé, Carine Rosignoli, Nathalie Taquet, Laurent F Hennequin
Targeting the Tumor Necrosis Factor α signalling with antibodies has led to a revolution in the treatment of psoriasis. Locally inhibiting Tumor Necrosis Factor α Converting Enzyme (TACE or ADAM17) could potentially mimic those effects and help treat mild to moderate psoriasis, without the reported side effect of systemic TACE inhibitors. Efforts to identify new TACE inhibitors are presented here. Enzymatic SAR as well as ADME and physico-chemistry data are presented. This study culminated in the identification of potent enzymatic inhibitors...
April 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28109308/semaphorin-7a-as-a-potential-immune-regulator-and-promising-therapeutic-target-in-rheumatoid-arthritis
#9
Jianmin Xie, Hao Wang
BACKGROUND: Semaphorin 7A (Sema7A) is expressed by several different classes of lymphoid and myeloid cells and is a potent immunomodulator. We examined the role of Sema7A in modulating cellular immune responses and to provide experimental data validating the therapeutic potential of Sema7A in rheumatoid arthritis (RA). METHODS: Soluble Sema7A (sSema7A) levels in the serum and synovial fluid from patients with RA or osteoarthritis, as well as cytokine secretions, were analyzed with an enzyme-linked immunosorbent assay...
January 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27863335/il-6-trans-signaling-is-another-pathway-to-upregulate-osteopontin
#10
Takaaki Uchibori, Kazuyuki Matsuda, Takahiro Shimodaira, Mitsutoshi Sugano, Takeshi Uehara, Takayuki Honda
BACKGROUND: Osteopontin (OPN) is a pro-fibrotic molecule upregulated by pro-inflammatory cytokines. Interleukin (IL)-6 functions downstream of IL-1β and has unique signal pathways: classic- or trans-signaling via membrane-bound IL-6R or soluble IL-6R (sIL-6R). We investigated the effect of IL-6 trans-signaling on the upregulation of OPN. METHODS: We used THP-1 cells and THP-1 macrophages differentiated from THP-1 cells using phorbol 12-myristate 13-acetate (PMA)...
November 15, 2016: Cytokine
https://www.readbyqxmd.com/read/27725819/sustained-immune-complex-mediated-reduction-in-cd16-expression-after-vaccination-regulates-nk-cell-function
#11
Martin R Goodier, Chiara Lusa, Sam Sherratt, Ana Rodriguez-Galan, Ron Behrens, Eleanor M Riley
Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27599715/stimulated-release-and-functional-activity-of-surface-expressed-metalloproteinase-adam17-in-exosomes
#12
Esther Groth, Jessica Pruessmeyer, Aaron Babendreyer, Julian Schumacher, Tobias Pasqualon, Daniela Dreymueller, Shigeki Higashiyama, Inken Lorenzen, Joachim Grötzinger, Didier Cataldo, Andreas Ludwig
By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here report that stimulation of lung epithelial A549 tumor cells with phorbol-12-myristate-13-acetate (PMA) leads to the downregulation of the surface expressed mature form of ADAM17 without affecting ADAM10 expression. This reduction could not be sufficiently explained by metalloproteinase-mediated degradation, dynamin-mediated internalization or microdomain redistribution of ADAM17...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27513608/the-role-of-rnase-7-in-innate-cutaneous-defense-against-pseudomonas-aeruginosa
#13
Franziska Rademacher, Maren Simanski, Lena Schröder, Michael Mildner, Jürgen Harder
The ribonuclease RNase 7 is a major skin-derived human antimicrobial protein expressed in keratinocytes. Here we show that the gram-negative pathogen Pseudomonas aeruginosa secretes factor(s) that induced RNase 7 gene and protein expression in human primary keratinocytes. The metalloprotease inhibitor marimastat, the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the EGFR blocking antibody cetuximab significantly attenuated this induction indicating an important role of the EGFR for the P. aeruginosa-mediated RNase 7 induction...
August 11, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27469341/targeting-adam17-sheddase-activity-in-cancer
#14
REVIEW
Armando Rossello, Elisa Nuti, Silvano Ferrini, Marina Fabbi
A disintegrin and metalloprotease (ADAM)17 is a sheddase, capable of releasing the ectodomains of membrane proteins such as growth factors (e.g. Epidermal Growth Factor Receptor ligands), cytokines and their receptors, adhesion and signaling molecules. These activities regulate several physiological and pathological processes including inflammation, tumor growth and metastatic progression. In this review, we will summarize ADAM17 biology and focus on its role in cancer and the possible usage of ADAM17 inhibitors in cancer therapy...
2016: Current Drug Targets
https://www.readbyqxmd.com/read/27460023/considerations-on-inhibition-approaches-for-proinflammatory-functions-of-adam-proteases
#15
Daniela Dreymueller, Andreas Ludwig
Proteases of the disintegrin and metalloproteinase (ADAM) family mediate the proteolytic shedding of various surface molecules including cytokine precursors, adhesion molecules, growth factors, and receptors. Within the vasculature ADAM10 and ADAM17 regulate endothelial permeability, transendothelial leukocyte migration, and the adhesion of leukocytes and platelets. In vivo studies show that both proteases are implicated in several inflammatory pathologies, for example, edema formation, leukocyte infiltration, and thrombosis...
June 2017: Platelets
https://www.readbyqxmd.com/read/27237127/heightened-cleavage-of-axl-receptor-tyrosine-kinase-by-adam-metalloproteases-may-contribute-to-disease-pathogenesis-in-sle
#16
Jacob J Orme, Yong Du, Kamala Vanarsa, Jessica Mayeux, Li Li, Azza Mutwally, Cristina Arriens, Soyoun Min, Jack Hutcheson, Laurie S Davis, Benjamin F Chong, Anne B Satterthwaite, Tianfu Wu, Chandra Mohan
Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27115328/the-adams-family-of-proteases-as-targets-for-the-treatment-of-cancer
#17
Maeve Mullooly, Patricia M McGowan, John Crown, Michael J Duffy
The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins...
August 2, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27076628/secretome-signature-identifies-adam17-as-novel-target-for-radiosensitization-of-non-small-cell-lung-cancer
#18
Ashish Sharma, Sabine Bender, Martina Zimmermann, Oliver Riesterer, Angela Broggini-Tenzer, Martin N Pruschy
PURPOSE: Ionizing radiation (IR) induces intracellular signaling processes as part of a treatment-induced stress response. Here we investigate IR-induced ADAM17 activation and the role of ADAM17-shed factors for radiation resistance in non-small cell lung cancer. EXPERIMENTAL DESIGN: Large-scale secretome profiling was performed using antibody arrays. Secretion kinetics of ADAM17 substrates was determined using ELISA across multiple in vitro and in vivo models of non-small cell lung cancer...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26993100/apoptosis-induced-ectodomain-shedding-of-hypoxia-regulated-carbonic-anhydrase-ix-from-tumor-cells-a-double-edged-response-to-chemotherapy
#19
Ivana Vidlickova, Franck Dequiedt, Lenka Jelenska, Olga Sedlakova, Michal Pastorek, Stanislav Stuchlik, Jaromir Pastorek, Miriam Zatovicova, Silvia Pastorekova
BACKGROUND: Carbonic anhydrase IX (CA IX) is a tumor-associated, highly active, transmembrane carbonic anhydrase isoform regulated by hypoxia and implicated in pH control and adhesion-migration-invasion. CA IX ectodomain (ECD) is shed from the tumor cell surface to serum/plasma of patients, where it can signify cancer prognosis. We previously showed that the CA IX ECD release is mediated by disintegrin and metalloproteinase ADAM17. Here we investigated the CA IX ECD shedding in tumor cells undergoing apoptosis in response to cytotoxic drugs, including cycloheximide and doxorubicin...
March 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/26919242/areca-nut-components-stimulate-adam17-il-1%C3%AE-pge2-and-8-isoprostane-production-in-oral-keratinocyte-role-of-reactive-oxygen-species-egf-and-jak-signaling
#20
Mei-Chi Chang, Chiu-Po Chan, Yi-Jane Chen, Hsiang-Chi Hsien, Ya-Ching Chang, Sin-Yuet Yeung, Po-Yuan Jeng, Ru-Hsiu Cheng, Liang-Jiunn Hahn, Jiiang-Huei Jeng
Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production...
March 29, 2016: Oncotarget
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