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https://www.readbyqxmd.com/read/28792672/constitutive-loss-and-acute-pharmacological-manipulation-of-erbb4-signaling-do-not-affect-attention-and-inhibitory-control-in-mice
#1
Elena Marchisella, Ruud Wijnands, Bastijn Koopmans, Sabine Spijker, Maarten Loos
The receptor tyrosine kinase ErbB4 and its ligand trophic factors of the neuregulin (NRG) family have been associated with schizophrenia and other mental disorders in human genetic studies. In vivo studies in mice have shown how abnormal Nrg-ErbB4 signaling leads to deviant behaviors relevant to distinct aspects of schizophrenia, including hyperactivity, sensory gating deficits, working and spatial memory deficits and impaired social behavior. However, so far little is known on the role of ErbB4 in attention and inhibitory control, two aspects of executive functions that are impaired in schizophrenia...
August 9, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28791649/isolation-of-human-mesenchymal-stem-cells-for-studying-erbb-receptor-signaling
#2
Chao Chen, Hongxing Jiang
ErbB receptor signaling plays pivotal roles in tumorigenesis, cancer development, and drug resistance. A better understanding of ErbB signaling is required to achieve better clinical outcomes in cancer treatment. With increasing evidence showing the link between human mesenchymal stem cells (MSCs) and cancer, there is a growing interest in studying the role of ErbB receptor signaling in the regulation of MSCs. For this purpose, obtaining quality primary human MSCs is of great importance. This chapter describes the method of isolating primary human MSCs, aiming to offer researchers of this field a useful tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791637/application-of-immunofluorescence-staining-to-study-erbb-family-of-receptor-tyrosine-kinases
#3
Babak Nami, Zhixiang Wang
Immunofluorescence staining is an effective method for visualizing ErbB family of receptor tyrosine kinases and to monitor their expression, phosphorylation, and localization in individual cells. However, immunofluorescence staining for membrane proteins is required preserving integrity of cell membrane intact by protecting the cells from organic solvents. Permeabilization of cells may increase nonspecific intracellular background signal as an inevitable result. This chapter describes procedures for the application of indirect immunofluorescence staining for ErbB receptors in adherent and suspended cells as well as in paraffin-embedded tissue sections...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#4
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28783046/epiregulin-and-egfr-interactions-are-involved-in-pain-processing
#5
Loren J Martin, Shad B Smith, Arkady Khoutorsky, Claire A Magnussen, Alexander Samoshkin, Robert E Sorge, Chulmin Cho, Noosha Yosefpour, Sivaani Sivaselvachandran, Sarasa Tohyama, Tiffany Cole, Thang M Khuong, Ellen Mir, Dustin G Gibson, Jeffrey S Wieskopf, Susana G Sotocinal, Jean Sebastien Austin, Carolina B Meloto, Joseph H Gitt, Christos Gkogkas, Nahum Sonenberg, Joel D Greenspan, Roger B Fillingim, Richard Ohrbach, Gary D Slade, Charles Knott, Ronald Dubner, Andrea G Nackley, Alfredo Ribeiro-da-Silva, G Gregory Neely, William Maixner, Dmitri V Zaykin, Jeffrey S Mogil, Luda Diatchenko
The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9...
August 7, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28769575/distinct-prognostic-values-of-alcohol-dehydrogenase-mrna-expression-in-pancreatic-adenocarcinoma
#6
Xiwen Liao, Rui Huang, Xiaoguang Liu, Chuangye Han, Long Yu, Shijun Wang, Na Sun, Bopei Li, Xin Ning, Tao Peng
BACKGROUND: Alcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD). MATERIALS AND METHODS: An RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28751244/cost-effectiveness-analysis-of-afatinib-versus-gefitinib-for-first-line-treatment-of-advanced-egfr-mutated-advanced-non-small-cell-lung-cancers
#7
Christos Chouaid, Laura Luciani, Katell LeLay, Pascal Do, Jaafar Bennouna, Maurice Perol, Denis Moro-Sibilot, Alain Vergnengre, Gérard de Pouvourville
BACKGROUND: The irreversible ErbB-family-blocker afatinib and the reversible EGFR tyrosine-kinase-inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase-2b LUX-Lung 7 trial for first-line treatment of advanced EGFR-mutation-positive non-small-cell lung cancers (EGFRm+ NSCLCs). Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib vs...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28750640/impact-of-somatic-pi3k-pathway-and-erbb-family-mutations-on-pathological-complete-response-pcr-in-her2-positive-breast-cancer-patients-who-received-neoadjuvant-her2-targeted-therapies
#8
Sinead Toomey, Alexander J Eustace, Joanna Fay, Katherine M Sheehan, Aoife Carr, Malgorzata Milewska, Stephen F Madden, Ausra Teiserskiene, Elaine W Kay, Norma O'Donovan, William Gallagher, Liam Grogan, Oscar Breathnach, Janice Walshe, Catherine Kelly, Brian Moulton, M John Kennedy, Guiseppe Gullo, Arnold D Hill, Colm Power, Deirdre Duke, Niamh Hambly, John Crown, Bryan T Hennessy
BACKGROUND: The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies...
July 27, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28750448/-role-of-the-human-erbb-family-receptors-in-urothelial-carcinoma-of-the-bladder-mrna-expression-status-and-prognostic-relevance
#9
Philipp Erben, Felix Wezel, Ralph Wirtz, Thomas Martini, Doron Stein, Cleo-Aaron Weis, Arndt Hartmann, Christian Bolenz
Background Altered expression of epidermal growth factor (EGF) family (ErbB) receptors in urothelial carcinoma of the urinary bladder (UCB) has been associated with adverse outcomes. Given the limited treatment options in UCB, EGFR and HER2 (ERBB2) represent established therapeutic targets in other entities. We assessed the expression of ErbB family receptors (ERBB1 - 4) on mRNA levels in correlation with histopathological and clinical parameters in patients treated with radical cystectomy (RC). Methods 94 patients (female = 22; male = 72; median age: 66...
August 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28739265/role-of-adam10-in-intestinal-crypt-homeostasis-and-tumorigenesis
#10
Peter J Dempsey
A disintegrin and metalloproteinases (ADAMs) are a family of multidomain, membrane-anchored proteases that regulate diverse cellular functions, including cell adhesion, migration, proteolysis and other cell signaling events. Catalytically-active ADAMs act as ectodomain sheddases that proteolytically cleave type I and type II transmembrane proteins and some GPI-anchored proteins from the cellular surface. ADAMs can also modulate other cellular signaling events through a process known as regulated intramembrane proteolysis (RIP)...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731464/trophoblast-survival-signaling-during-human-placentation-requires-hsp70-activation-of-mmp2-mediated-hbegf-shedding
#11
Chandni V Jain, Philip Jessmon, Charbel T Barrak, Alan D Bolnick, Brian A Kilburn, Michael Hertz, D Randall Armant
Survival of trophoblast cells in the low oxygen environment of human placentation requires metalloproteinase-mediated shedding of HBEGF and downstream signaling. A matrix metalloproteinase (MMP) antibody array and quantitative RT-PCR revealed upregulation of MMP2 post-transcriptionally in human first trimester HTR-8/SVneo trophoblast cells and placental villous explants exposed to 2% O2. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. Because α-amanitin inhibited the upregulation of HBEGF, differentially expressed genes were identified by next-generation sequencing of RNA from trophoblast cells cultured at 2% O2 for 0, 1, 2 and 4 h...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#12
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#13
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#14
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28715775/evolution-of-anti-her2-therapies-for-cancer-treatment
#15
REVIEW
Sagun Parakh, Hui K Gan, Adam C Parslow, Ingrid J G Burvenich, Antony W Burgess, Andrew M Scott
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28701734/long-noncoding-rna-expression-profile-changes-associated-with-dietary-energy-in-the-sheep-testis-during-sexual-maturation
#16
Yanli Zhang, Hua Yang, Le Han, Fengzhe Li, Tingting Zhang, Jing Pang, Xu Feng, Caifang Ren, Shengyong Mao, Feng Wang
Spermatogenesis can be affected by nutrition, which operates through normal physiological processes by changing the testicular mass and hormone levels profoundly. However, little is known regarding how testis development is regulated by long noncoding RNA (lncRNA). In this study, we investigated the effects of high-grain (HG) feeding on testis development during sexual maturation mediated by lncRNA. The HG diet group showed an increase in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and testosterone (T) levels, and in the number of sperm in the seminiferous tubules compared with the hay-fed group (p  < 0...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699206/kiaa1199-a-novel-regulator-of-mek-erk-induced-schwann-cell-dedifferentiation
#17
Angélique Boerboom, Céline Reusch, Alexandra Pieltain, Alain Chariot, Rachelle Franzen
The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. It is currently believed that different levels of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the identification of new regulators of MEK1/ERK1/2 signalling could help to decipher the context-specific aspects driving the effects of this pathway on SC plasticity. In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity...
July 12, 2017: Glia
https://www.readbyqxmd.com/read/28698179/a-novel-regulatory-mechanism-of-smooth-muscle-%C3%AE-actin-expression-by-nrg-1-circacta2-mir-548f-5p-axis
#18
Yan Sun, Zhan Yang, Bin Zheng, Xin-Hua Zhang, Man-Li Zhang, Xue-Shan Zhao, Hong-Ye Zhao, Toru Suzuki, Jin-Kun Wen
Rationale: Neuregulin-1 (NRG-1) includes an extracellular EGF-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor (TGF)-β1,its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB receptor. However, NRG-1-ICD function in VSMCs remains unknown. Objective: Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Methods and Results: Immunofluorescence staining, Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that NRG-1 was expressed in rat, mouse and human VSMCs and was upregulated and cleaved in response to TGF-β1...
July 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28689251/genome-wide-analysis-of-dna-methylation-in-hyperoxia-exposed-newborn-rat-lung
#19
Chung-Ming Chen, Yi-Chun Liu, Yue-Jun Chen, Hsiu-Chu Chou
PURPOSE: Oxygen therapy is often required to treat newborn infants with respiratory disorders. Prolonged exposure of neonatal rats to hyperoxia reduced alveolar septation, increased terminal air space size, and increased lung fibrosis; these conditions are very similar to those of human bronchopulmonary dysplasia. Epigenetic regulation of gene expression plays a crucial role in bronchopulmonary dysplasia development. METHOD: We reared Sprague-Dawley rat pups in either room air (RA, n = 24) or an atmosphere containing 85% O2 (n = 26) from Postnatal Days 1 to 14...
July 8, 2017: Lung
https://www.readbyqxmd.com/read/28683304/inhibition-of-the-schizophrenia-associated-microrna-mir-137-disrupts-nrg1%C3%AE-neurodevelopmental-signal-transduction
#20
Kristen Therese Thomas, Bart Russell Anderson, Niraj Shah, Stephanie Elaine Zimmer, Daniel Hawkins, Arielle Nicole Valdez, Qiaochu Gu, Gary Jonathan Bassell
Genomic studies have repeatedly associated variants in the gene encoding the microRNA miR-137 with increased schizophrenia risk. Bioinformatic predictions suggest that miR-137 regulates schizophrenia-associated signaling pathways critical to neural development, but these predictions remain largely unvalidated. In the present study, we demonstrate that miR-137 regulates neuronal levels of p55γ, PTEN, Akt2, GSK3β, mTOR, and rictor. All are key proteins within the PI3K-Akt-mTOR pathway and act downstream of neuregulin (Nrg)/ErbB and BDNF signaling...
July 5, 2017: Cell Reports
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