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https://www.readbyqxmd.com/read/29774782/the-neuroprotective-effect-of-ethanol-intoxication-in-tbi-is-associated-with-the-suppression-of-erbb-signaling-in-pv-positive-interneurons
#1
Akila Chandrasekar, Florian Olde Heuvel, Martin Wepler, Rida Rehman, Annette Palmer, Alberto Catanese, Birgit Linkus, Albert Ludolph, Tobias Boeckers, Markus Huber-Lang, Peter Radermacher, Francesco Roselli
Ethanol intoxication (EI) is a frequent comorbidity of TBI, but the impact of EI on TBI pathogenic cascades and prognosis is unclear: although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways and pathogenic cascades, in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5g/Kg) before trauma enhances behavioral recovery in a weight-drop TBI model; neuronal survival in the injured somatosensory cortex was enhanced by EI...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29769179/rna-profiles-of-circulating-tumor-cells-and-extracellular-vesicles-for-therapy-stratification-of-metastatic-breast-cancer-patients
#2
Corinna Keup, Pawel Mach, Bahriye Aktas, Mitra Tewes, Hans-Christian Kolberg, Siegfried Hauch, Markus Sprenger-Haussels, Rainer Kimmig, Sabine Kasimir-Bauer
BACKGROUND: Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS: Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points...
May 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29729836/prognostic-value-of-egfr-family-expression-in-lymph-node-negative-esophageal-squamous-cell-carcinoma-patients
#3
Weiwei Yu, Xi Yang, Li Chu, Kuaile Zhao, Haiquan Chen, Jiaqing Xiang, Yawei Zhang, Hecheng Li, Weixin Zhao, Menghong Sun, Qiao Wei, Xiaolong Fu, Congying Xie, Zhengfei Zhu
The human epidermal growth factor receptor (EGFR) family has been widely studied in cancer, however, the prognostic role of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma (ESCC) patients have not been invalidated. This study was designed to determine the prognostic value of EGFR family expression in a population of lymph node-negative ESCC patients treated with curative resection. EGFR family protein expression was examined by immunohistochemical analysis of tissue microarrays of 94 patients with lymph node-negative ESCC after radical esophagectomy with three-field lymphadenectomy...
April 30, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29725898/rates-of-tp53-mutation-are-significantly-elevated-in-african-american-patients-with-gastric-cancer
#4
Elke J A H van Beek, Jonathan M Hernandez, Debra A Goldman, Jeremy L Davis, Kaitlin McLaughlin, R Taylor Ripley, Teresa S Kim, Laura H Tang, Jaclyn F Hechtman, Jian Zheng, Marinela Capanu, Nikolaus Schultz, David M Hyman, Marc Ladanyi, Michael F Berger, David B Solit, Yelena Y Janjigian, Vivian E Strong
BACKGROUND: Gastric adenocarcinoma is a heterogenous disease that results from complex interactions between environmental and genetic factors, which may contribute to the disparate outcomes observed between different patient populations. This study aimed to determine whether genomic differences exist in a diverse population of patients by evaluating tumor mutational profiles stratified by race. METHODS: All patients with gastric adenocarcinoma between 2012 and 2016 who underwent targeted next-generation sequencing of cancer genes by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform were identified...
May 3, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29718453/molecular-landscape-of-erbb2-erbb3-mutated-colorectal-cancer
#5
Jonathan M Loree, Ann M Bailey, Amber M Johnson, Yao Yu, Wenhui Wu, Christopher A Bristow, Jennifer S Davis, Kenna R Shaw, Russell Broaddus, Kimberly C Banks, Richard B Lanman, Funda Meric-Bernstam, Michael J Overman, Scott Kopetz, Kanwal Raghav
Background: Despite growing therapeutic relevance of ERBB2 amplifications in colorectal cancer (CRC), little is known about ERBB2/ERBB3 mutations. We aimed to characterize these subsets of CRC. Methods: We performed a retrospective analysis of 419 CRC patients from MD Anderson (MDACC) and 619 patients from the Nurses' Health Study (NHS)/Health Professionals Follow-Up Study (HPFS) with tissue sequencing, clinicopathologic, mutational, and consensus molecular subtype (CMS) profiles of ERBB2/ERBB3 mutant patients...
April 27, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29715459/mesenchymal-stem-cells-drive-paclitaxel-resistance-in-erbb2-erbb3-coexpressing-breast-cancer-cells-via-paracrine-of-neuregulin-1
#6
Jin Chen, Qun Ren, Yuanming Cai, Tingting Lin, Weimin Zuo, Jin Wang, Rong Lin, Ling Zhu, Ping Wang, Huiyue Dong, Hu Zhao, Lianghu Huang, Yunfeng Fu, Shunliang Yang, Jianming Tan, Xiaopeng Lan, Shuiliang Wang
We had previously demonstrated that increased expression of ErbB3 is required for ErbB2-mediated paclitaxel resistance in breast cancer cells. In the present study, we have explored the possible role of mesenchymal stem cells (MSCs) in regulating the paclitaxel-sensitivity of ErbB2/ErbB3-coexpressing breast cancer cells. We show that human umbilical cord-derived MSCs express significantly higher level of neuregulin-1 as compared with ErbB2/ErbB3-coexpressing breast cancer cells themselves. Coculture or treatment with conditioned medium of MSCs not only decreases the anti-proliferation effect of paclitaxel on ErbB2/ErbB3-coexpressing breast cancer cells, but also significantly inhibits paclitaxel-induced apoptosis...
April 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29702367/targeting-natural-compounds-against-her2-kinase-domain-as-potential-anticancer-drugs-applying-pharmacophore-based-molecular-modelling-approaches
#7
Shailima Rampogu, Minky Son, Ayoung Baek, Chanin Park, Rabia Mukthar Rana, Amir Zeb, Saravanan Parameswaran, Keun Woo Lee
Human epidermal growth factor receptors are implicated in several types of cancers characterized by aberrant signal transduction. This family comprises of EGFR (ErbB1), HER2 (ErbB2, HER2/neu), HER3 (ErbB3), and HER4 (ErbB4). Amongst them, HER2 is associated with breast cancer and is one of the most valuable targets in addressing the breast cancer incidences. For the current investigation, we have performed 3D-QSAR based pharmacophore search for the identification of potential inhibitors against the kinase domain of HER2 protein...
April 20, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29700358/premyogenic-progenitors-derived-from-human-pluripotent-stem-cells-expand-in-floating-culture-and-differentiate-into-transplantable-myogenic-progenitors
#8
Fusako Sakai-Takemura, Asako Narita, Satoru Masuda, Toshifumi Wakamatsu, Nobuharu Watanabe, Takashi Nishiyama, Ken'ichiro Nogami, Matthias Blanc, Shin'ichi Takeda, Yuko Miyagoe-Suzuki
Human induced pluripotent stem cells (hiPSCs) are a potential source for cell therapy of Duchenne muscular dystrophy. To reliably obtain skeletal muscle progenitors from hiPSCs, we treated hiPS cells with a Wnt activator, CHIR-99021 and a BMP receptor inhibitor, LDN-193189, and then induced skeletal muscle cells using a previously reported sphere-based culture. This protocol greatly improved sphere formation efficiency and stably induced the differentiation of myogenic cells from hiPS cells generated from both healthy donors and a patient with congenital myasthenic syndrome...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29683256/the-immunoglobulin-like-domain-of-neuregulins-potentiates-erbb3-her3-activation-and-cellular-proliferation
#9
Ariana Centa, Ruth Rodríguez-Barrueco, Juan Carlos Montero, Atanasio Pandiella
The Neuregulins (NRGs) represent a large family of membrane-anchored growth factors, whose deregulation may contribute to the pathogenesis of several tumours. In fact, targeting of NRG-activated pathways has demonstrated clinical benefit. To improve the efficacy of anti-NRG therapies, it is essential to gain insights into the regions of NRGs that favour their pro-oncogenic properties. Here we have addressed the protumorigenic impact of different NRG domains. To do this, deletion mutants affecting different NRG domains were expressed in 293 and MCF7 cells...
April 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29674508/combined-braf-and-hsp90-inhibition-in-patients-with-unresectable-braf-v600e-mutant-melanoma
#10
Zeynep Eroglu, Yian Ann Chen, Geoffrey T Gibney, Jeffrey S Weber, Ragini R Kudchadkar, Nikhil I Khushalani, Joseph Markowitz, Andrew S Brohl, Leticia F Tetteh, Howida Ramadan, Gina Arnone, Jiannong Li, Xiuhua Zhao, Ritin Sharma, Lancia N F Darville, Bin Fang, Inna Smalley, Jane L Messina, John M Koomen, Vernon K Sondak, Keiran S M Smalley
PURPOSE: BRAF inhibitors are clinically active in patients with advanced BRAFV600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. METHODS: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose...
April 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29610121/response-to-erbb3-directed-targeted-therapy-in-nrg1-rearranged-cancers
#11
Alexander Drilon, Romel Somwar, Biju P Mangatt, Henrik Edgren, Patrice Desmeules, Anja Ruusulehto, Roger S Smith, Lukas Delasos, Morana Vojnic, Andrew J Plodkowski, Joshua Sabari, Kenneth Ng, Joseph Montecalvo, Jason Chang, Huichun Tai, William W Lockwood, Victor Martinez, Gregory J Riely, Charles M Rudin, Mark G Kris, Maria E Arcila, Christopher Matheny, Ryma Benayed, Natasha Rekhtman, Marc Ladanyi, Gopinath Ganji
NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMAs) of the lung. The oncoprotein binds ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 monoclonal antibody therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase 1 trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four NRG1-rearranged IMA patients (including the index patient post-GSK2849330)...
April 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29568012/modulation-of-the-neuregulin-1-erbb-system-after-skeletal-muscle-denervation-and-reinnervation
#12
Michela Morano, Giulia Ronchi, Valentina Nicolò, Benedetta Elena Fornasari, Alessandro Crosio, Isabelle Perroteau, Stefano Geuna, Giovanna Gambarotta, Stefania Raimondo
Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes...
March 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29560723/a-high-confidence-interactome-for-rnf41-built-on-multiple-orthogonal-assays
#13
Delphine Masschaele, Joris Wauman, Giel Vandemoortele, Delphine De Sutter, Leentje De Ceuninck, Sven Eyckerman, Jan Tavernier
Ring finger protein 41 (RNF41) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of many proteins including ErbB3 receptors, BRUCE and parkin. Next to this, RNF41 regulates the intracellular trafficking of certain JAK2-associated cytokine receptors by ubiquitinating and suppressing USP8 which in turn destabilizes the ESCRT-0 complex. To further elucidate the function of RNF41 we used different orthogonal approaches to reveal the RNF41 protein complex: Affinity Purification-Mass Spectrometry, BioID and Virotrap...
March 21, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29549161/dual-inhibition-of-igf-1r-and-erbb3-enhances-the-activity-of-gemcitabine-and-nab-paclitaxel-in-preclinical-models-of-pancreatic-cancer
#14
Adam J Camblin, Emily A Pace, Sharlene Adams, Michael D Curley, Victoria Rimkunas, Lin Nie, Gege Tan, Troy Bloom, Sergio Iadevaia, Jason Baum, Charlene Minx, Akos Czibere, Chrystal U Louis, Daryl C Drummond, Ulrik B Nielsen, Birgit Schoeberl, J Marc Pipas, Robert M Straubinger, Vasileios Askoxylakis, Alexey A Lugovskoy
PURPOSE: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29546711/the-pseudopod-system-for-axon-glia-interactions-stimulation-and-isolation-of-schwann-cell-protrusions-that-form-in-response-to-axonal-membranes
#15
Yannick Poitelon, M Laura Feltri
In the peripheral nervous system, axons dictate the differentiation state of Schwann cells. Most of this axonal influence on Schwann cells is due to juxtacrine interactions between axonal transmembrane molecules (e.g., the neuregulin growth factor) and receptors on the Schwann cell (e.g., the ErbB2/ErbB3 receptor). The fleeting nature of this interaction together with the lack of synchronicity in the development of the Schwann cell population limits our capability to study this phenomenon in vivo. Here we present a simple Boyden Chamber-based method to study this important cell-cell interaction event...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29545886/expression-and-secretion-of-neuregulin-1-in-cardiac-microvascular-endothelial-cells-treated-with-angiogenic-factors
#16
Chengqiang Wu, Chun Gui, Lang Li, Yiheng Pang, Zhongli Tang, Jing Wei
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29545332/acquired-resistance-to-a-met-antibody-in-vivo-can-be-overcome-by-the-met-antibody-mixture-sym015
#17
Sofie Ellebæk Pollmann, Valerie S Calvert, Shruti Rao, Simina M Boca, Subha Madhavan, Ivan D Horak, Andreas Kjaer, Emanuel F Petricoin, Michael Kragh, Thomas Tuxen Poulsen
Failure of clinical trials due to development of resistance to MET-targeting therapeutic agents is an emerging problem. Mechanisms of acquired resistance to MET tyrosine kinase inhibitors are well described, whereas characterization of mechanisms of resistance toward MET-targeting antibodies is limited. This study investigated mechanisms underlying in vivo resistance to two antibody therapeutics currently in clinical development: an analogue of the MET-targeting antibody emibetuzumab and Sym015, a mixture of two antibodies targeting non-overlapping epitopes of MET...
March 15, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29515761/frequent-nrg1-fusions-in-caucasian-pulmonary-mucinous-adenocarcinoma-predicted-by-phospho-erbb3-expression
#18
Domenico Trombetta, Paolo Graziano, Aldo Scarpa, Angelo Sparaneo, Giulio Rossi, Antonio Rossi, Massimo Di Maio, Davide Antonello, Andrea Mafficini, Federico Pio Fabrizio, Maria Carmina Manzorra, Teresa Balsamo, Flavia Centra, Michele Simbolo, Angela Pantalone, Michela Notarangelo, Paola Parente, Maria Cecilia Lucia Dimitri, Antonio Bonfitto, Fabiola Fiordelisi, Clelia Tiziana Storlazzi, Alberto L'Abbate, Marco Taurchini, Evaristo Maiello, Vito Michele Fazio, Lucia Anna Muscarella
NRG1 fusions were recently reported as a new molecular feature of Invasive Mucinous Adenocarcinoma (IMA) of the lung. The NRG1 chimeric ligand acts as a strong inductor of phosphorylation and tyrosine kinase activity of the ErbB2/ErbB3 heterodimer, thus enhancing the PI3K-AKT/MAPK pathways. The NRG1 fusions were widely investigated in Asian IMA cohorts, whereas just anecdotal information are available about the occurrence of NRG1 fusions in IMA Caucasian population. Here we firstly explored a large Caucasian cohort of 51 IMAs and 34 non-IMA cases for the occurrence of NRG1 rearrangements by fluorescent in situ hybridization (FISH) and RNA target sequencing...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29506988/phase-ii-study-of-the-dual-egfr-her3-inhibitor-duligotuzumab-mehd7945a-versus-cetuximab-in-combination-with-folfiri-in-second-line-ras-wild-type-metastatic-colorectal-cancer
#19
Andrew G Hill, Michael P Findlay, Matthew E Burge, Christopher Jackson, Pilar Garcia Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffery, Maria Di Bartolomeo, John Bridgewater, Andrew L Coveler, Manuel Hidalgo, Amy V Kapp, Roxana I Sufan, Bruce B McCall, William D Hanley, Elicia M Penuel, Andrea Pirzkall, Josep Tabernero
Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental Design: Metastatic colorectal cancer (mCRC) patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomly assigned patients, 98 had RAS ex2/3 wild-type. Duligotuzumab provided no progression-free survival (PFS) or overall survival (OS) benefit compared with cetuximab, although there was a trend for a lower objective response rate (ORR) in the duligotuzumab arm...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29503661/identification-of-shared-molecular-signatures-indicate-the-susceptibility-of-endometriosis-to-multiple-sclerosis
#20
Amit Katiyar, Sujata Sharma, Tej P Singh, Punit Kaur
Women with endometriosis (EMS) appear to be at a higher risk of developing other autoimmune diseases predominantly multiple sclerosis (MS). Though EMS and MS are evidently diverse in their phenotype, they are linked by a common autoimmune condition or immunodeficiency which could play a role in the expansion of endometriosis and possibly increase the risk of developing MS in women with EMS. However, the common molecular links connecting EMS with MS are still unclear. We conducted a meta-analysis of microarray experiments focused on EMS and MS with their respective controls...
2018: Frontiers in Genetics
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