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Amphiregulin

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https://www.readbyqxmd.com/read/27887604/variable-ventilation-improves-pulmonary-function-and-reduces-lung-damage-without-increasing-bacterial-translocation-in-a-rat-model-of-experimental-pneumonia
#1
Raquel F de Magalhães, Cynthia S Samary, Raquel S Santos, Milena V de Oliveira, Nazareth N Rocha, Cintia L Santos, Jamil Kitoko, Carlos A M Silva, Caroline L Hildebrandt, Cassiano F Goncalves-de-Albuquerque, Adriana R Silva, Hugo C Faria-Neto, Vanessa Martins, Vera L Capelozzi, Robert Huhle, Marcelo M Morales, Priscilla Olsen, Paolo Pelosi, Marcelo Gama de Abreu, Patricia R M Rocco, Pedro L Silva
BACKGROUND: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia...
November 25, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27835572/sprouty2-inhibits-amphiregulin-induced-down-regulation-of-e-cadherin-and-cell-invasion-in-human-ovarian-cancer-cells
#2
Jung-Chien Cheng, Hsun-Ming Chang, Siyuan Xiong, Wai-Kin So, Peter C K Leung
Similar to Drosophila Sprouty (SPRY), mammalian SPRY proteins inhibit the receptor tyrosine kinase-mediated activation of cellular signaling pathways. SPRY2 expression levels have been shown to be down-regulated in human ovarian cancer, and patients with low SPRY2 expression have significantly poorer survival than those with high SPRY2 expression. In addition, epidermal growth factor receptor (EGFR) is overexpressed in human ovarian cancer and is associated with more aggressive clinical behavior and a poor prognosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826039/amphiregulin-enhances-vegf-a-production-in-human-chondrosarcoma-cells-and-promotes-angiogenesis-by-inhibiting-mir-206-via-fak-c-src-pkc%C3%AE-pathway
#3
Chao-Qun Wang, Yu-Wen Huang, Shih-Wei Wang, Yuan-Li Huang, Chun-Hao Tsai, Yong-Ming Zhao, Bi-Fei Huang, Guo-Hong Xu, Yi-Chin Fong, Chih-Hsin Tang
Chondrosarcoma is the second most common primary malignancy of bone after myeloma and osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). The expression of VEGF-A has been recognized as a prognostic marker in angiogenesis. Amphiregulin (AR), an epidermal growth factor receptor ligand, promotes tumor proliferation, metastasis and angiogenesis. However, the role of AR in VEGF-A expression and angiogenesis in human chondrosarcoma remains largely unknown...
November 5, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27812543/duox1-mediates-persistent-epithelial-egfr-activation-mucous-cell-metaplasia-and-airway-remodeling-during-allergic-asthma
#4
Aida Habibovic, Milena Hristova, David E Heppner, Karamatullah Danyal, Jennifer L Ather, Yvonne M W Janssen-Heininger, Charles G Irvin, Matthew E Poynter, Lennart K Lundblad, Anne E Dixon, Miklos Geiszt, Albert van der Vliet
Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite-induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1)...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27783866/areg-triggered-egfr-activation-confers-in-vivo-crizotinib-resistance-of-eml4-alk-lung-cancer-and-circumvention-by-egfr-inhibitors
#5
Hirokazu Taniguchi, Shinji Takeuchi, Koji Fukuda, Takayuki Nakagawa, Sachiko Arai, Shigeki Nanjo, Tadaaki Yamada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement...
October 26, 2016: Cancer Science
https://www.readbyqxmd.com/read/27765922/g-protein-coupled-receptor-81-promotes-a-malignant-phenotype-in-breast-cancer-through-angiogenic-factor-secretion
#6
Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Kyeong Su Park, Seorim Park, Kyun Heo, Young-Kyo Seo, Dong-Young Noh, Sung Ho Ryu, Pann-Ghill Suh
G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27764839/impact-of-tumour-ras-braf-status-in-a-first-line-study-of-panitumumab-folfiri-in-patients-with-metastatic-colorectal-cancer
#7
Meinolf Karthaus, Ralf-Dieter Hofheinz, Laurent Mineur, Henry Letocha, Richard Greil, Josef Thaler, Eva Fernebro, Kelly S Oliner, Michael Boedigheimer, Brian Twomey, Ying Zhang, Gaston Demonty, Claus-Henning Köhne
BACKGROUND: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC). METHODS: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression. RESULTS: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease...
November 8, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27761886/comparison-between-effects-of-pressure-support-and-pressure-controlled-ventilation-on-lung-and-diaphragmatic-damage-in-experimental-emphysema
#8
Gisele de A Padilha, Lucas F B Horta, Lillian Moraes, Cassia L Braga, Milena V Oliveira, Cíntia L Santos, Isalira P Ramos, Marcelo M Morales, Vera Luiza Capelozzi, Regina C S Goldenberg, Marcelo Gama de Abreu, Paolo Pelosi, Pedro L Silva, Patricia R M Rocco
BACKGROUND: In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. METHODS: Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks...
December 2016: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/27756321/egfr-transactivation-contributes-to-neuroinflammation-in-streptococcus-suis-meningitis
#9
Xiao-Pei Yang, Ji-Yang Fu, Rui-Cheng Yang, Wen-Tong Liu, Tao Zhang, Bo Yang, Ling Miao, Bei-Bei Dou, Chen Tan, Huan-Chun Chen, Xiang-Ru Wang
BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic bacterial pathogen in both humans and animals, which can cause high morbidity and mortality. Meningitis is one of the major clinical manifestations of SS2 infection. However, the specific process of SS2 meningitis and its molecular mechanisms remain unclear. Epidermal growth factor receptor (EGFR) has been reported to initiate transduction of intracellular signals and regulate host inflammatory responses. Whether and how EGFR contributes to the development of S...
October 19, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27713123/abnormal-amphiregulin-expression-correlates-with-gastric-cancer-prognosis
#10
Bing Wang, Hongmei Yong, Huijun Zhu, Daguang Ni, Sijie Tang, Shu Zhang, Wei Wang, Yan Zhou, Wei Zhao, Guipeng Ding, Jin Zhu, Xiaohua Li, Zhenqing Feng
Gastric cancer (GC) is a global health issue with a high mortality rate. Early diagnosis and tracking of GC is a challenge due to a lack of reliable tools. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family that activates growth signaling upon binding of EGF receptors. Elevated AREG expression is associated with various pathological conditions, including cancer. Here, we investigated whether increased AREG expression is a disease indicator and/or prognostic biomarker for GC. We used tissue microarray and quantitative real-time polymerase chain reaction to assess AREG expression in clinical tissue specimens at various stages of GC and a conducted bioinformatics analysis to evaluate the value of AREG over-expression as a GC biomarker...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27709733/egf-amphiregulin-interplay-in-airway-stem-progenitor-cells-links-the-pathogenesis-of-smoking-induced-lesions-in-the-human-airway-epithelium
#11
Wu-Lin Zuo, Jing Yang, Kazunori Gomi, IonWa Chao, Ronald G Crystal, Renat Shaykhiev
The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of epidermal growth factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells...
October 6, 2016: Stem Cells
https://www.readbyqxmd.com/read/27669890/epidermal-growth-factor-egf-receptor-ligand-based-molecular-staging-predicts-prognosis-in-head-and-neck-squamous-cell-carcinoma-partly-due-to-deregulated-egf-induced-amphiregulin-expression
#12
Jian Gao, Camilla H Ulekleiv, Trond S Halstensen
BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients...
September 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27642633/adam17-substrate-release-in-proximal-tubule-drives-kidney-fibrosis
#13
Eirini Kefaloyianni, Muthu Lakshmi Muthu, Jakob Kaeppler, Xiaoming Sun, Venkata Sabbisetti, Athena Chalaris, Stefan Rose-John, Eitan Wong, Irit Sagi, Sushrut S Waikar, Helmut Rennke, Benjamin D Humphreys, Joseph V Bonventre, Andreas Herrlich
Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates' receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27635238/egf-receptor-ligands-recent-advances
#14
REVIEW
Bhuminder Singh, Graham Carpenter, Robert J Coffey
Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR...
2016: F1000Research
https://www.readbyqxmd.com/read/27631986/progesterone-based-therapy-protects-against-influenza-by-promoting-lung-repair-and-recovery-in-females
#15
Olivia J Hall, Nathachit Limjunyawong, Meghan S Vermillion, Dionne P Robinson, Nicholas Wohlgemuth, Andrew Pekosz, Wayne Mitzner, Sabra L Klein
Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27625357/late-acute-graft-versus-host-disease-a-prospective-analysis-of-clinical-outcomes-and-circulating-angiogenic-factors
#16
Shernan G Holtan, Nandita Khera, John E Levine, Xiaoyu Chai, Barry Storer, Hien D Liu, Yoshihiro Inamoto, George L Chen, Sebastian Mayer, Mukta Arora, Jeanne Palmer, Mary E D Flowers, Corey S Cutler, Alexander Lukez, Sally Arai, Aleksandr Lazaryan, Laura F Newell, Christa Krupski, Madan H Jagasia, Iskra Pusic, William Wood, Anne S Renteria, Gregory Yanik, William J Hogan, Elizabeth Hexner, Francis Ayuk, Ernst Holler, Phandee Watanaboonyongcharoen, Yvonne A Efebera, James L M Ferrara, Angela Panoskaltsis-Mortari, Daniel Weisdorf, Stephanie J Lee, Joseph Pidala
Late acute (LA) graft vs. host disease (GVHD) is persistent, recurrent, or new onset acute GVHD symptoms occurring after 100 days post-allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, mortality, and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n=909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, IQR 128-204) days after HCT...
September 13, 2016: Blood
https://www.readbyqxmd.com/read/27621461/spry1-regulates-mammary-epithelial-morphogenesis-by-modulating-egfr-dependent-stromal-paracrine-signaling-and-ecm-remodeling
#17
Zuzana Koledova, Xiaohong Zhang, Charles Streuli, Robert B Clarke, Ophir D Klein, Zena Werb, Pengfei Lu
The role of the local microenvironment in influencing cell behavior is central to both normal development and cancer formation. Here, we show that sprouty 1 (SPRY1) modulates the microenvironment to enable proper mammary branching morphogenesis. This process occurs through negative regulation of epidermal growth factor receptor (EGFR) signaling in mammary stroma. Loss of SPRY1 resulted in up-regulation of EGFR-extracellular signal-regulated kinase (ERK) signaling in response to amphiregulin and transforming growth factor alpha stimulation...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27599715/stimulated-release-and-functional-activity-of-surface-expressed-metalloproteinase-adam17-in-exosomes
#18
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/27570430/prognostic-and-predictive-biomarkers-in-metastatic-colorectal-cancer-anti-egfr-therapy
#19
Cristiana Lo Nigro, Vincenzo Ricci, Daniela Vivenza, Cristina Granetto, Teresa Fabozzi, Emanuela Miraglio, Marco C Merlano
AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling. METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21(st), 2016 using these following terms: ''colorectal cancer'', "predictive biomarkers'', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ''EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miRNA" and "antibody-dependent cell-mediated cytotoxicity (ADCC) activity"...
August 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27561911/adam17-and-egfr-regulate-il-6-receptor-and-amphiregulin-mrna-expression-and-release-in-cigarette-smoke-exposed-primary-bronchial-epithelial-cells-from-patients-with-chronic-obstructive-pulmonary-disease-copd
#20
Marta Stolarczyk, Gimano D Amatngalim, Xiao Yu, Mieke Veltman, Pieter S Hiemstra, Bob J Scholte
Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls...
August 2016: Physiological Reports
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