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https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28683007/prophylactic-effects-of-secretion-metabolites-of-dairy-lactobacilli-through-downregulation-of-erbb-2-and-erbb-3-genes-on-colon-cancer-cells
#10
Zeinab Faghfoori, Bahram Pourghassem Gargari, Amir Saber, Maryam Seyyedi, Siavash Fazelian, Ahmad Yari Khosroushahi
Colon cancer is one of the most prevalent cancers, and intestinal microbial community plays a pivotal role in colorectal tumor genesis. Probiotics as live microorganisms may be able to exert an anticancer effect in colon cancer. The aim of this study was to isolate and identify Lactobacillus spp. from traditional dairy products with probiotic properties and to investigate their anticancer effects through ErbB-2 and ErbB-3 gene expression in colon cancer cells. The isolated lactobacilli from yogurt and cheese samples were molecularly identified by blasting of 16-23s rDNA region PCR sequenced products...
July 4, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28682884/microarray-expression-profile-of-circular-rnas-in-chronic-thromboembolic-pulmonary-hypertension
#11
Ran Miao, Ying Wang, Jun Wan, Dong Leng, Juanni Gong, Jifeng Li, Yan Liang, Zhenguo Zhai, Yuanhua Yang
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3'- and 5'-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28681313/an-independent-survival-prognostic-role-for-human-epidermal-growth-factor-receptor-2-in-gastric-cancer-evidence-from-a-meta-analysis
#12
Y Wang, L He, Y Cheng
BACKGROUND: Some studies have suggested that human epidermal growth factor receptor 2 (HER2) positive is associated with poor outcomes in gastric cancer (GC), whereas another inconsistent studies make the situation confused. This meta-analysis was performed to determine whether HER2 played an independent prognostic role in clinicopathological characteristics and survival outcomes of GC. PATIENTS AND METHODS: Combination of GC and human epidermal growth factor 2 or HER2 or HER2/neu or erbB-2 or cerbB-2 or c-erbB2 or CD340 or p185 were used as key words...
July 5, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28680960/efficacy-and-safety-results-of-the-afatinib-expanded-access-program
#13
Edward S Kim, Balazs Halmos, Ingrid F Kohut, Taral Patel, Regan D Rostorfer, Alexander I Spira, Agnieszka Cseh, John McKay, Gudrun Wallenstein, Kathryn F Mileham
INTRODUCTION: Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy. METHODS: The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring EGFR mutations...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28679031/effect-of-social-interactions-on-hippocampal-protein-expression-in-animal-dominant-and-submissive-model-of-behavioral-disorders
#14
Natalia Borovok, Elimelech Nesher, Michal Reichenstein, Tatiana Tikhonova, Yishai Levin, Albert Pinhasov, Izhak Michaelevski
Psychiatric conditions often arise from social interactions, necessary for optimal mental functioning. Dominance and submissiveness are opposite poles of behavior, stemming from processes of social interactions between members inside one group or species. Extreme dominance/submissiveness expressions in humans is accompanied by mental impairments, mania or depression. Here, taking advantage of selectively bred dominant and submissive mice, we assessed protein expression profiles in the social interaction context...
July 5, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28676676/identifying-pathways-modulating-sleep-duration-from-genomics-to-transcriptomics
#15
Karla V Allebrandt, Maris Teder-Laving, Paola Cusumano, Goar Frishman, Rosa Levandovski, Andreas Ruepp, Maria P L Hidalgo, Rodolfo Costa, Andres Metspalu, Till Roenneberg, Cristiano De Pittà
Recognizing that insights into the modulation of sleep duration can emerge by exploring the functional relationships among genes, we used this strategy to explore the genome-wide association results for this trait. We detected two major signalling pathways (ion channels and the ERBB signalling family of tyrosine kinases) that could be replicated across independent GWA studies meta-analyses. To investigate the significance of these pathways for sleep modulation, we performed transcriptome analyses of short sleeping flies' heads (knockdown for the ABCC9 gene homolog; dSur)...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28675388/disrupted-hippocampal-neuregulin-1-erbb3-signaling-and-dentate-gyrus-granule-cell-alterations-in-suicide
#16
I Mahar, B Labonte, S Yogendran, E Isingrini, L Perret, M A Davoli, A Rachalski, B Giros, G Turecki, N Mechawar
Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28671339/role-of-erbb-her-family-of-receptor-tyrosine-kinases-in-cholangiocyte-biology
#17
REVIEW
Anna Pellat, Javier Vaquero, Laura Fouassier
The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions including differentiation, proliferation, survival and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from completed...
July 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28660665/integrated-microrna-and-gene-expression-profiling-reveals-the-crucial-mirnas-in-curcumin-anti-lung-cancer-cell-invasion
#18
Jian-Wei Zhan, De-Min Jiao, Yi Wang, Jia Song, Jin-Hong Wu, Li-Jun Wu, Qing-Yong Chen, Sheng-Lin Ma
BACKGROUND: Curcumin (diferuloylmethane) has chemopreventive and therapeutic properties against many types of tumors, both in vitro and in vivo. Previous reports have shown that curcumin exhibits anti-invasive activities, but the mechanisms remain largely unclear. METHODS: In this study, both microRNA (miRNA) and messenger RNA (mRNA) expression profiles were used to characterize the anti-metastasis mechanisms of curcumin in human non-small cell lung cancer A549 cell line...
June 29, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28656214/her2-regulates-cancer-stem-like-cell-phenotype-in-alk-translocated-nsclc
#19
Tiia Honkanen, Emmi Wilenius, Peppi Koivunen, Jussi P Koivunen
We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28649882/neratinib-for-the-treatment-of-her2-positive-early-stage-breast-cancer
#20
Isabel Echavarria, Sara López-Tarruella, Iván Márquez-Rodas, Yolanda Jerez, Miguel Martin
Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting...
June 26, 2017: Expert Review of Anticancer Therapy
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