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https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#1
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065855/tyrosine-kinase-phosphatase-inhibitors-decrease-dengue-virus-production-in-hepg2-cells
#2
Thawornchai Limjindaporn, Jutatip Panaampon, Shilu Malakar, Sansanee Noisakran, Pathai Yenchitsomanus
Dengue virus is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. High rates of dengue virus replication and virion production are related to disease severity. To identify anti-DENV compounds, we performed cell-based ELISA testing to detect the level of DENV E protein expression. Among a total of 83 inhibitors, eight were identified as inhibitors with antiviral activity. Epidermal growth factor receptor inhibitor II (EGFR/ErbB-2/ErbB-4 inhibitor II) and protein tyrosine phosphatase inhibitor IV (PTP inhibitor IV) significantly inhibited dengue virus production and demonstrated low toxicity in hepatocyte cell lines...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28061785/short-term-early-exposure-to-lapatinib-confers-lifelong-protection-from-mammary-tumor-development-in-mmtv-erbb-2-transgenic-mice
#3
Zhikun Ma, Amanda B Parris, Zhengzheng Xiao, Erin W Howard, Stanley D Kosanke, Xiaoshan Feng, Xiaohe Yang
BACKGROUND: Although chemopreventative agents targeting the estrogen/estrogen receptor (ER) pathway have been effective for ER(+) breast cancers, prevention of hormone receptor-negative breast cancers, such as Her2/erbB-2(+) breast cancers, remains a significant issue. Previous studies have demonstrated that administration of EGFR/erbB-2-targeting lapatinib to MMTV-erbB-2 transgenic mice inhibited mammary tumor development. The prevention, however, was achieved by prolonged high dose exposure...
January 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#4
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059646/irreversible-changes-occurring-in-long-term-denervated-schwann-cells-affect-delayed-nerve-repair
#5
Giulia Ronchi, Michele Cillino, Giovanna Gambarotta, Benedetta Elena Fornasari, Stefania Raimondo, Pierfrancesco Pugliese, Pierluigi Tos, Adriana Cordova, Francesco Moschella, Stefano Geuna
OBJECTIVE Multiple factors may affect functional recovery after peripheral nerve injury, among them the lesion site and the interval between the injury and the surgical repair. When the nerve segment distal to the lesion site undergoes chronic degeneration, the ensuing regeneration (when allowed) is often poor. The aims of the current study were as follows: 1) to examine the expression changes of the neuregulin 1/ErbB system during long-term nerve degeneration; and 2) to investigate whether a chronically denervated distal nerve stump can sustain nerve regeneration of freshly axotomized axons...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28059040/natural-products-targeting-egfr-signaling-pathways-as-potential-anticancer-drugs
#6
Xiaoyu Wang, Linfeng Xu, Yuanzhi Lao, Hongmei Zhang, Hongxi Xu
The epidermal growth factor receptor (EGFR) belongs to ErbB family of tyrosine kinases, which plays an important role in the regulation of cell proliferation, survival, differentiation, and metastasis. In addition, tumors develop resistance to EGFR inhibitors due to the presence or development of point mutations in the tyrosine kinase domain of the receptor. There is an urgent need to develop new anti-EGFR agents with strong therapeutic activities. As the majority of anticancer drugs are of natural origin, natural products are a valuable source for the identification and development of novel treatment options for cancer...
January 5, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28043142/a-comprehensive-analysis-of-candidate-gene-signatures-in-oral-squamous-cell-carcinoma
#7
X Li, R Sun, X Geng, S Wang, D Zen, J Pei, J Yang, Y Fan, H Jiang, P Yang, C Li
Aimed to unravel the molecular mechanism of Oral squamous cell carcinoma (OSCC). With microarray dataset GSE30784, differentially expressed genes (DEGs) were identified between OSCC and control samples. The DEGs overlapped with genes obtained from online database MalaCards were determined as OSCCDEG, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 5177 up-regulated and 6081 down-regulated DEGs were identified between OSCC and control. Out of the DEGs, 451 genes were overlapped with the 704 genes gained from MalaCards and regarded as "OSCCDEG"...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28040546/whole-genome-sequencing-reveals-the-mutational-landscape-of-metastatic-small-cell-gallbladder-neuroendocrine-carcinoma-gb-scnec
#8
Maolan Li, Fatao Liu, Yijian Zhang, Xiangsong Wu, Wenguang Wu, Xu-An Wang, Shuai Zhao, Shibo Liu, Haibin Liang, Fei Zhang, Qiang Ma, Shanshan Xiang, Huaifeng Li, Lin Jiang, Yunping Hu, Wei Gong, Yun Zhang, Tieliang Ma, Kai Zhang, Yun Liu, Yingbin Liu
Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. We identified approximately 900 high-quality somatic single nucleotide variants (SNVs) and small insertions and deletions (INDELs), 109 of which were shared by both the primary and metastatic tumor tissues. Somatic non-synonymous coding variations with damaging impact in HMCN1 and CDH10 were observed in both the primary and metastatic tissue specimens...
December 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28029660/phenotypic-characterization-of-circulating-tumor-cells-in-triple-negative-breast-cancer-patients
#9
Sofia Agelaki, Melina Dragolia, Harris Markonanolaki, Saad Alkahtani, Christos Stournaras, Vassilis Georgoulias, Galatea Kallergi
INTRODUCTION: Patients with triple negative breast cancer (TNBC), are considered as a poor prognosis group for whom no targeted therapies are currently available. The aim of the present study was to phenotypically characterize their CTCs in order to explore potential therapeutic targets. METHODS: PBMC's cytospins were prepared from 45 early (before and after adjuvant chemotherapy), 10 metastatic TNBC and 21 hormone receptor (HR) -positive patients. The expression of Cytokeratins (CK), ER, PR, EGFR and HER2 on CTCs was assessed using immunofluoresence staining and ARIOL analysis...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028299/gene-expression-in-obstetric-antiphospholipid-syndrome-a-systematic-review
#10
M Muhammad Aliff, S Muhammad Shazwan, M M Nur Fariha, A R Hayati, A R Nur Syahrina, M Maizatul Azma, A H Nazefah, S Jameela, A A Asral Wirda
BACKGROUND: Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/27998938/agent-based-re-engineering-of-erbb-signaling-a-modeling-pipeline-for-integrative-systems-biology
#11
Arya A Das, T A Darsana, Elizabeth Jacob
MOTIVATION: Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments...
December 20, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27994634/serum-microrna-profiling-and-bioinformatics-of-patients-with-spleen-deficiency-syndrome
#12
Ze-Min Yang, Long-Hui Chen, Min Hong, Ying-Yu Chen, Xiao-Rong Yang, Si-Meng Tang, Qian-Fa Yuan, Zhen-Yu He, Wei-Wen Chen
To investigate serum microRNA (miRNA) profile and bioinformatics of patients with spleen-deficiency syndrome (SDS) and explore pathogenesis of SDS patients from miRNA levels, 10 patients with type 2 diabetes mellitus (T2DM), within which 5 patients were with SDS and the remaining were with blood stasis syndrome (BSS), and 5 healthy volunteers were recruited. Serum miRNA profiles of SDS patients were identified by quantitative PCR array. Target prediction and functional annotation for miRNAs were performed by miRSystem database...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27993643/effects-of-neuregulin-ggf2-cimaglermin-alfa-dose-and-treatment-frequency-on-left-ventricular-function-in-rats-following-myocardial-infarction
#13
Tom J Parry, Anindita Ganguly, Erika L Troy, J Luis Guerrero, Jennifer F Iaci, Maya Srinivas, Andrea M Vecchione, Donald C Button, Craig S Hackett, Ronald Zolty, Douglas B Sawyer, Anthony O Caggiano
Neuregulins are important growth factors involved in cardiac development and response to stress. Certain isoforms and fragments of neuregulin have been found to be cardioprotective. The effects of a full-length neuregulin-1β isoform, glial growth factor 2 (GGF2; USAN/INN; also called cimaglermin) were investigated in vitro. Various dosing regimens were then evaluated for their effects on left ventricular (LV) function in rats with surgically-induced myocardial infarction. In vitro, GGF2 bound with high affinity to erythroblastic leukemia viral oncogene (ErbB) 4 receptors, potently promoted Akt phosphorylation, as well as reduced cell death following doxorubicin exposure in HL1 cells...
December 16, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27993557/inhibition-of-endoplasmic-reticulum-stress-by-neuregulin-1-protects-against-myocardial-ischemia-reperfusion-injury
#14
Shan-Juan Fang, Peng-Yang Li, Chun-Mei Wang, Yi Xin, Wei-Wei Lu, Xiao-Xia Zhang, Song Zuo, Chang-Sheng Ma, Chao-Shu Tang, Shao-Ping Nie, Yong-Fen Qi
Neuregulin-1 (NRG-1), an endogenously produced polypeptide, is the ligand of cardiomyocyte ErbB receptors, with cardiovascular protective effects. In the present study, we explored whether the cardioprotective effect of NRG-1 against I/R injury is mediated by inhibiting myocardial endoplasmic reticulum (ER) stress. In vitro, NRG-1 directly inhibited the upregulation of ER stress markers such as glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12 induced by the ER stress inducers tunicamycin or dithiothreitol in both neonatal and adult ventricular myocytes...
December 16, 2016: Peptides
https://www.readbyqxmd.com/read/27988307/interleukin-6-and-neuregulin-1-as-regulators-of-utrophin-expression-via-the-activation-of-nrg-1-erbb-signaling-pathway-in-mdx-cells
#15
Nevenka Juretić, Josefina Díaz, Felipe Romero, Gustavo González, Enrique Jaimovich, Nora Riveros
Duchenne muscular dystrophy (DMD) is a neuromuscular disease originated by mutations in the dystrophin gene. A promising therapeutic approach deals with functional substitution of dystrophin by utrophin, a structural homolog that might be able to compensate dystrophin absence in DMD muscle fibers. It has been described that both interleukin-6 (IL-6) and neuregulin-1 (NRG-1; Heregulin-HRG) induce utrophin expression in skeletal muscle. We investigated a possible functional link among IL-6, NRG-1 and utrophin, in normal (C57) and dystrophic (mdx) skeletal muscle cells...
December 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27979883/publisher-s-note-modulation-of-dorsal-root-ganglion-development-by-erbb-signaling-and-the-scaffold-protein-sorbs3-by-malmquist-et-al-development-doi-10-1242-dev-084640
#16
https://www.readbyqxmd.com/read/27934102/fluorescent-kinase-probes-enabling-identification-and-dynamic-imaging-of-her2-cells
#17
Heajin Lee, Wenjun Liu, Adrienne S Brown, Ralf Landgraf, James N Wilson
The human epidermal growth factor receptor, EGFR/ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small molecule kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. We report ERBB2 (also HER2) targeting kinase probes that exhibit a "turn-on" emission response upon binding...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#18
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#19
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907855/lc-ms-ms-assay-for-the-quantitation-of-the-tyrosine-kinase-inhibitor-neratinib-in-human-plasma
#20
Brian F Kiesel, Robert A Parise, Alvin Wong, Kiana Keyvanjah, Samuel Jacobs, Jan H Beumer
Neratinib is an orally available tyrosine kinase inhibitor targeting HER2 (ERBB2) and EGFR (ERBB). It is being clinically evaluated for the treatment of breast and other solid tumors types as a single agent or in combination with other chemotherapies. In support of several phase I/II clinical trials investigating neratinib combinations, we developed and validated a novel LC-MS/MS assay for the quantification of neratinib in 100μL of human plasma with a stable isotopic internal standard. Analytes were extracted from plasma using protein precipitation and evaporation of the resulting supernatant followed by resuspension...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
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