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https://www.readbyqxmd.com/read/27933395/influence-of-the-her-receptor-ligand-system-on-sensitivity-to-cetuximab-and-trastuzumab-in-gastric-cancer-cell-lines
#1
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/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/27815440/identification-of-novel-cd4-t-cell-subsets-in-the-target-tissue-of-sj%C3%A3-gren-s-syndrome-and-their-differential-regulation-by-the-lymphotoxin-light-signaling-axis
#3
Scott Haskett, Jian Ding, Wei Zhang, Alice Thai, Patrick Cullen, Shanqin Xu, Britta Petersen, Galina Kuznetsov, Luke Jandreski, Stefan Hamann, Taylor L Reynolds, Norm Allaire, Timothy S Zheng, Michael Mingueneau
Despite being one of the most common rheumatologic diseases, there is still no disease-modifying drug for primary Sjögren's syndrome (pSS). Advancing our knowledge of the target tissue has been limited by the low dimensionality of histology techniques and the small size of human salivary gland biopsies. In this study, we took advantage of a molecularly validated mouse model of pSS to characterize tissue-infiltrating CD4(+) T cells and their regulation by the lymphotoxin/LIGHT signaling axis. Novel cell subsets were identified by combining highly dimensional flow and mass cytometry with transcriptomic analyses...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27813674/induction-of-tissue-factor-pathway-inhibitor-2-by-hcg-regulates-periovulatory-gene-expression-and-plasmin-activity
#4
Muraly Puttabyatappa, Linah F Al-Alem, Farnosh Zakerkish, Katherine L Rosewell, Mats Brännström, Thomas E Curry
A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling...
November 4, 2016: Endocrinology
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/27756321/egfr-transactivation-contributes-to-neuroinflammation-in-streptococcus-suis-meningitis
#8
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/27748490/integrating-targeted-gene-expression-and-a-skin-model-system-to-identify-functional-inhibitors-of-the-uv-activated-p38-map-kinase
#9
Amaal Abrahams, Nicolas Mouchet, Nicolas Gouault, Françoise Lohézic Le Dévéhat, Myriam Le Roch, Isabelle Rouaud, David Gilot, Marie-Dominique Galibert
The stress-activated p38α MAP Kinase is an integral and critical component of the UV-induced inflammatory response. Despite the advances in recent years in the development of p38 kinase inhibitors, validation of these compounds in the diseased models remains limited. Based on the pharmacological profile of p38α inhibitor lead compound, SB203580, we synthesized a series of pyrrole-derivatives. Using UV-irradiated human skin punch-biopsies and cell cultures, we identified and validated the inhibitory activity of the derivatives by quantitatively measuring their effect on the expression of p38α target genes using real-time PCR...
November 30, 2016: Photochemical & Photobiological Sciences
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/27646113/overexpression-of-histone-demethylase-fbxl10-leads-to-enhanced-migration-in-mouse-embryonic-fibroblasts
#13
Magdalena Rohde, Elisabeth Sievers, Andreas Janzer, Dominica Willmann, Angela Egert, Hubert Schorle, Roland Schüle, Jutta Kirfel
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations. Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks...
September 16, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27643521/cover-image-volume-232-number-1-january-2017
#14
Areg Zingiryan, Nicholas H Farina, Kristiaan H Finstad, Janet L Stein, Jane B Lian, Gary S Stein
Cover: The cover image, by Nicholas H Farina et al., is based on the From the Bench Paper Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA, DOI: 10.1002/jcp.25384.
January 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27642633/adam17-substrate-release-in-proximal-tubule-drives-kidney-fibrosis
#15
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
#16
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/27634876/a-microrna-runx1-runx2-network-regulates-prostate-tumor-progression-from-onset-to-adenocarcinoma-in-tramp-mice
#17
Nicholas H Farina, Areg Zingiryan, Jacqueline A Akech, Cody J Callahan, Huimin Lu, Janet L Stein, Lucia R Languino, Gary S Stein, Jane B Lian
While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27631986/progesterone-based-therapy-protects-against-influenza-by-promoting-lung-repair-and-recovery-in-females
#18
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
#19
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/27567953/gene-expression-of-the-egf-system-a-prognostic-model-in-non-small-cell-lung-cancer-patients-without-activating-egfr-mutations
#20
Birgitte Sandfeld-Paulsen, Birgitte Holst Folkersen, Torben Riis Rasmussen, Peter Meldgaard, Boe S Sorensen
OBJECTIVES: Contradicting results have been demonstrated for the expression of the epidermal growth factor receptor (EGFR) as a prognostic marker in non-small cell lung cancer (NSCLC). The complexity of the EGF system with four interacting receptors and more than a dozen activating ligands is a likely explanation. The aim of this study is to demonstrate that the combined network of receptors and ligands from the EGF system is a prognostic marker. MATERIAL AND METHODS: Gene expression of the receptors EGFR, HER2, HER3, HER4, and the ligands AREG, HB-EGF, EPI, TGF-α, and EGF was measured by quantitative polymerase chain reaction in tumor samples from 100 NSCLC patients without EGFR activating mutations...
August 2016: Translational Oncology
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