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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
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...
October 20, 2016: British Journal of Cancer
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
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...
October 17, 2016: Photochemical & Photobiological Sciences
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
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 EGFR ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of EGF-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity...
October 6, 2016: Stem Cells
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
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
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
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
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
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
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
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
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
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
Jung-Chien Cheng, Lanlan Fang, Hsun-Ming Chang, Ying-Pu Sun, Peter C K Leung
Sprouty2 (SPRY2) is an important intracellular regulator for epidermal growth factor receptor (EGFR)-mediated ERK1/2 signaling. In human granulosa cells, although SPRY2 is expressed, its regulation and function remains complete unknown and must be defined. Our previous study has shown that human chorionic gonadotropin (hCG)/luteinizing hormone (LH) up-regulates the expression levels of EGF-like growth factor, amphiregulin (AREG), which subsequently contributes to the hCG/LH-induced COX-2 expression and PGE2 production...
2016: Scientific Reports
Takashi Haneda, Yasutomo Imai, Ryosuke Uchiyama, Orie Jitsukawa, Kiyofumi Yamanishi
Mutations of the transglutaminase 1 gene (TGM1) are a major cause of autosomal recessive congenital ichthyoses (ARCIs) that are associated with defects in skin barrier structure and function. However, the molecular processes induced by the transglutaminase 1 deficiency are not fully understood. The aim of the present study was to uncover those processes by analysis of cutaneous molecular signatures. Gene expression profiles of wild-type and Tgm1-/-epidermis were assessed using microarrays. Gene ontology analysis of the data showed that genes for innate defense responses were up-regulated in Tgm1-/-epidermis...
2016: PloS One
Yun Mi Lee, Yu-Ri Lee, Chan-Sik Kim, Kyuhyung Jo, Eunjin Sohn, Jin Sook Kim, Junghyun Kim
BACKGROUND: Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model...
2016: BMC Complementary and Alternative Medicine
R Scott Kemp, Areg Danagoulian, Ruaridh R Macdonald, Jayson R Vavrek
How does one prove a claim about a highly sensitive object such as a nuclear weapon without revealing information about the object? This paradox has challenged nuclear arms control for more than five decades. We present a mechanism in the form of an interactive proof system that can validate the structure and composition of an object, such as a nuclear warhead, to arbitrary precision without revealing either its structure or composition. We introduce a tomographic method that simultaneously resolves both the geometric and isotopic makeup of an object...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
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