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https://www.readbyqxmd.com/read/28742111/axonal-outgrowth-neuropeptides-expression-and-receptors-tyrosine-kinase-phosphorylation-in-3d-organotypic-cultures-of-adult-dorsal-root-ganglia
#1
Estrela Neto, Cecília J Alves, Luís Leitão, Daniela M Sousa, Inês S Alencastre, Francisco Conceição, Meriem Lamghari
Limited knowledge from mechanistic studies on adult sensory neuronal activity was generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To fill this gap there is a real need to better characterize the adult dorsal root ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable for different approaches, ranging from basic neurobiology to regenerative therapies, to address the sensory nervous system in adult stage. We conducted a direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic culture focusing on axonal growth, neuropeptides expression and receptors tyrosine kinase (RTK) activation associated with neuronal survival, proliferation and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#2
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28730475/characterization-of-ligand-binding-to-pseudokinases-using-a-thermal-shift-assay
#3
Isabelle S Lucet, James M Murphy
The protocol herein describes a robust and proven method for the measurement of pseudokinase-ligand interaction using a fluorescence-based thermal shift assay (TSA). Pseudokinases are kinase-like proteins that have recently emerged as crucial regulatory modules of signal transduction pathways and may well represent a novel class of drug targets. However, unlike kinases, the regulatory activity of pseudokinases is mainly conferred through protein-protein interactions. Understanding the mechanisms that underlie pseudokinase conformational changes through ligand binding and how such conformational changes can tune signaling pathways is a necessary step to unravel their biological functions...
2017: Methods in Molecular Biology
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
#4
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
#5
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/28707296/ebp1-regulates-myogenic-differentiation-of-myoblast-cells-via-smad2-3-signaling-pathway
#6
Minli Yu, Huan Wang, Zhen Liu, Yinglin Lu, Debing Yu, Dongfeng Li, Wenxing Du
Regulation of skeletal muscle development requires many of the regulatory networks that are fundamental to developmental myogenesis. ErbB3 binding protein-1 (Ebp1) is involved in the control of myoblasts development in chicken. However, the expression and biological functions of Ebp1 in the progress of myogenesis are unclear. This study focused on determining the effect of Ebp1 on myogenic proliferation and differentiation using a primary myoblasts culture model. Ebp1 was found to upregulate in proliferating myoblasts and decrease at the early stage of myogenic differentiation...
July 13, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28695611/prediction-of-type-1-diabetes-using-a-genetic-risk-model-in-the-diabetes-autoimmunity-study-in-the-young
#7
Brigitte I Frohnert, Michael Laimighofer, Jan Krumsiek, Fabian J Theis, Christiane Winkler, Jill M Norris, Anette-Gabriele Ziegler, Marian J Rewers, Andrea K Steck
BACKGROUND: Genetic predisposition for type 1 diabetes (T1D) is largely determined by human leukocyte antigen (HLA) genes; however, over 50 other genetic regions confer susceptibility. We evaluated a previously reported 10-factor weighted model derived from the Type 1 Diabetes Genetics Consortium to predict the development of diabetes in the Diabetes Autoimmunity Study in the Young (DAISY) prospective cohort. Performance of the model, derived from individuals with first-degree relatives (FDR) with T1D, was evaluated in DAISY general population (GP) participants as well as FDR subjects...
July 11, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28675388/disrupted-hippocampal-neuregulin-1-erbb3-signaling-and-dentate-gyrus-granule-cell-alterations-in-suicide
#8
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
#9
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/28670312/cervical-cancer-neoantigen-landscape-and-immune-activity-is-associated-with-human-papillomavirus-master-regulators
#10
Yong Qin, Suhendan Ekmekcioglu, Marie-Andrée Forget, Lorant Szekvolgyi, Patrick Hwu, Elizabeth A Grimm, Amir A Jazaeri, Jason Roszik
Human papillomaviruses (HPVs) play a major role in development of cervical cancer, and HPV oncoproteins are being targeted by immunotherapies. Although these treatments show promising results in the clinic, many patients do not benefit or the durability is limited. In addition to HPV antigens, neoantigens derived from somatic mutations may also generate an effective immune response and represent an additional and distinct immunotherapy strategy against this and other HPV-associated cancers. To explore the landscape of neoantigens in cervix cancer, we predicted all possible mutated neopeptides in two large sequencing data sets and analyzed whether mutation and neoantigen load correlate with antigen presentation, infiltrating immune cell types, and a HPV-induced master regulator gene expression signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28646138/uniting-the-neuro-developmental-and-immunological-hypotheses-neuregulin-1-receptor-erbb-and-toll-like-receptor-activation-in-first-episode-schizophrenia
#11
Szabolcs Kéri, Csilla Szabó, Oguz Kelemen
Current pathophysiological models of schizophrenia focus on neurodevelopmental and immunological mechanisms. We investigated a molecular pathway traditionally linked to the neurodevelopmental hypothesis (neuregulin 1 - ErbB), and pathogen-associated pattern recognition receptors associated with the immune hypothesis (Toll-like receptors, TLRs). We recruited 42 first-episode, drug-naïve patients with schizophrenia and 42 matched healthy control subjects. In monocytes TLR4/TLR5 and ErbB expressions were measured with flow-cytometry...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646072/genetic-and-environmental-interactions-modify-the-risk-of-diabetes-related-autoimmunity-by-6-years-of-age-the-teddy-study
#12
Jeffrey P Krischer, Kristian F Lynch, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar
OBJECTIVE: We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS: Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. SNPs came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS: Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children)...
June 23, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#13
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
September 2017: Glia
https://www.readbyqxmd.com/read/28597949/primary-islet-autoantibody-at-initial-seroconversion-and-autoantibodies-at-diagnosis-of-type-1-diabetes-as-markers-of-disease-heterogeneity
#14
Jorma Ilonen, Johanna Lempainen, Anna Hammais, Antti-Pekka Laine, Taina Härkönen, Jorma Toppari, Riitta Veijola, Mikael Knip
OBJECTIVE: The relationship between patterns of islet autoantibodies at diagnosis and specificity of the first islet autoantibody at the initiation of autoimmunity was analyzed with the aim of identifying patterns informative of the primary autoantibodies. METHODS: Information about a single first autoantibody at seroconversion and autoantibody data at diagnosis were available for 128 children participating in the follow-up cohort of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study...
June 9, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28591206/erbb3-a-potential-serum-biomarker-for-early-detection-and-therapeutic-target-for-devil-facial-tumour-1-dft1
#15
Dane A Hayes, Dale A Kunde, Robyn L Taylor, Stephen B Pyecroft, Sukhwinder Singh Sohal, Elizabeth T Snow
Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1's cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored...
2017: PloS One
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#16
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590920/hcarg-commd5-inhibits-erbb-receptor-driven-renal-cell-carcinoma
#17
Hiroyuki Matsuda, Carole G Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet, Johanne Tremblay
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570571/construction-and-analyses-of-the-microrna-target-gene-differential-regulatory-network-in-thyroid-carcinoma
#18
Ying-Ying Kang, Yang Liu, Ming-Li Wang, Min Guo, Yan Wang, Zhi-Feng Cheng
Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28570276/macrophage-infiltration-and-genetic-landscape-of-undifferentiated-uterine-sarcomas
#19
Joanna Przybyl, Magdalena Kowalewska, Anna Quattrone, Barbara Dewaele, Vanessa Vanspauwen, Sushama Varma, Sujay Vennam, Aaron M Newman, Michal Swierniak, Elwira Bakuła-Zalewska, Janusz A Siedlecki, Mariusz Bidzinski, Jan Cools, Matt van de Rijn, Maria Debiec-Rychter
Endometrial stromal tumors include translocation-associated low- and high-grade endometrial stromal sarcomas (ESS) and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of aggressive tumors and is often seen as a diagnosis of exclusion after ESS and leiomyosarcoma (LMS) have been ruled out. We performed a comprehensive analysis of gene expression, copy number variation, point mutations, and immune cell infiltrates in the largest series to date of all major types of uterine sarcomas to shed light on the biology of UUS and to identify potential novel therapeutic targets...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28542518/rnf41-interacts-with-the-vps52-subunit-of-the-garp-and-earp-complexes
#20
Delphine Masschaele, Leentje De Ceuninck, Joris Wauman, Dieter Defever, Frank Stenner, Sam Lievens, Frank Peelman, Jan Tavernier
RNF41 (Ring Finger Protein 41) is an E3 ubiquitin ligase involved in the intracellular sorting and function of a diverse set of substrates. Next to BRUCE and Parkin, RNF41 can directly ubiquitinate ErbB3, IL-3, EPO and RARα receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and routing. To further elucidate the molecular mechanism behind the role of RNF41 in intracellular transport we performed an Array MAPPIT (Mammalian Protein-Protein Interaction Trap) screen using an extensive set of proteins derived from the human ORFeome collection...
2017: PloS One
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