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Amphiregulin

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https://www.readbyqxmd.com/read/28137591/amphiregulin-suppresses-epithelial-cell-apoptosis-in-lipopolysaccharide-induced-lung-injury-in-mice
#1
Saiko Ogata-Suetsugu, Toyoshi Yanagihara, Naoki Hamada, Chika Ikeda-Harada, Tetsuya Yokoyama, Kunihiro Suzuki, Tomonobu Kawaguchi, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi
BACKGROUND AND OBJECTIVE: As a member of the epidermal growth factor family, amphiregulin contributes to the regulation of cell proliferation. Amphiregulin was reported to be upregulated in damaged lung tissues in patients with chronic obstructive pulmonary disease and asthma and in lung epithelial cells in a ventilator-associated lung injury model. In this study, we investigated the effect of amphiregulin on lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Acute lung injury was induced by intranasal instillation of LPS in female C57BL/6 mice, and the mice were given intraperitoneal injections of recombinant amphiregulin or phosphate-buffered saline 6 and 0...
January 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28074039/cd34-mesenchymal-cells-are-a-major-component-of-the-intestinal-stem-cells-niche-at-homeostasis-and-after-injury
#2
Igor Stzepourginski, Giulia Nigro, Jean-Marie Jacob, Sophie Dulauroy, Philippe J Sansonetti, Gérard Eberl, Lucie Peduto
The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28071680/loss-of-tricellular-tight-junction-protein-lsr-promotes-cell-invasion-and-migration-via-upregulation-of-tead1-areg-in-human-endometrial-cancer
#3
Hiroshi Shimada, Shyuetsu Abe, Takayuki Kohno, Seiro Satohisa, Takumi Konno, Syunta Takahashi, Tsubasa Hatakeyama, Chihiro Arimoto, Takuya Kakuki, Yakuto Kaneko, Ken-Ichi Takano, Tsuyoshi Saito, Takashi Kojima
Lipolysis-stimulated lipoprotein receptor (LSR) is a unique molecule of tricellular contacts of normal and cancer cells. We investigated how the loss of LSR induced cell migration, invasion and proliferation in endometrial cancer cell line Sawano. mRNAs of amphiregulin (AREG) and TEA domain family member 1 (TEAD1) were markedly upregulated by siRNA-LSR. In endometrial cancer tissues, downregulation of LSR and upregulation of AREG were observed together with malignancy, and Yes-associated protein (YAP) was present in the nuclei...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032593/the-impact-of-co-expression-of-wild-type-egfr-and-its-ligands-determined-by-immunohistochemistry-for-response-to-treatment-with-cetuximab-in-patients-with-metastatic-colorectal-cancer
#4
Said Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Seddon, Helmout Modjtahedi
Anti-EGFR mAbs cetuximab and panitumumab are routinely used for the treatment of patients with KRAS-wild type metastatic colorectal cancer (mCRC). However, in some patients their efficacy remains modest and with no clear association between the EGFR protein expression determined by PharmDx™ kit, and response to anti-EGFR therapies. Therefore, we investigated the relative expression and predictive value of wild-type EGFR (wtEGFR), mutated EGFRvIII and EGFR ligand proteins in mCRC patients treated with cetuximab...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27968833/myopia-in-china-a-population-based-cross-sectional-histological-and-experimental-study
#5
Jost B Jonas, Liang Xu, Wen Bin Wei, Ya Xing Wang, Wen Jun Jiang, Hong Sheng Bi, Songhomitra Panda-Jonas
BACKGROUND: The prevalence of myopia has markedly increased within the past three decades, in particular in China. Because of myopic retinopathy and myopia-associated glaucoma, myopia has become one of the leading blinding disorders. METHODS: Conducting population-based studies and school-based investigations, we assessed prevalence and incidence of myopia and associated factors in children, university students, and adults in urban and rural regions of different Chinese provinces...
October 2016: Lancet
https://www.readbyqxmd.com/read/27933395/influence-of-the-her-receptor-ligand-system-on-sensitivity-to-cetuximab-and-trastuzumab-in-gastric-cancer-cell-lines
#6
Julia Kneissl, Anja Hartmann, Nicole Pfarr, Franziska Erlmeier, Thomas Lorber, Simone Keller, Gwen Zwingenberger, Wilko Weichert, Birgit Luber
PURPOSE: Gastric cancer remains a major health concern, and improvement of the therapeutic options is crucial. Treatment with targeted therapeutics such as the EGFR-targeting antibody cetuximab or the HER2-targeting antibody trastuzumab is either ineffective or moderately effective in this disease, respectively. In this study, we analysed the involvement of the HER receptor ligands amphiregulin (AREG), epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF) and transforming growth factor alpha (TGFα) in the responsiveness of gastric cancer cell lines to cetuximab and trastuzumab...
December 8, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27923629/prognostic-value-of-rare-and-complex-mutations-in-egfr-and-serum-levels-of-soluble-egfr-and-its-ligands-in-non-small-cell-lung-carcinoma-patients
#7
Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi, Siamak Sabour, Abdolamir Allameh
BACKGROUND: A number of complex and rare mutations in epidermal growth factor receptor (EGFR) gene have been identified and the clinical implication of serum EGFR ligands has also been reported. However, the prognostic significance of these mutations and also the serum EGFR and its ligands in Non-Small Cell Lung Carcinoma (NSCLC) has remained a challenging issue. This study is aimed at finding the prognostic importance of EGFR rare mutations and serum EGFR, amphiregulin (AR), and TGF-α (Transforming Growth Factor-alpha) in NSCLC...
December 5, 2016: Clinical Biochemistry
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
#8
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
#9
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
#10
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...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27812543/duox1-mediates-persistent-epithelial-egfr-activation-mucous-cell-metaplasia-and-airway-remodeling-during-allergic-asthma
#11
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/amphiregulin-triggered-epidermal-growth-factor-receptor-activation-confers-in-vivo-crizotinib-resistance-of-eml4-alk-lung-cancer-and-circumvention-by-epidermal-growth-factor-receptor-inhibitors
#12
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...
January 2017: Cancer Science
https://www.readbyqxmd.com/read/27765922/g-protein-coupled-receptor-81-promotes-a-malignant-phenotype-in-breast-cancer-through-angiogenic-factor-secretion
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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