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https://www.readbyqxmd.com/read/28550306/a-novel-somatic-transforming-mutation-in-the-extracellular-domain-of-epidermal-growth-factor-receptor-identified-in-myeloproliferative-neoplasm
#1
D A Casolari, T Nguyen, C M Butcher, D G Iarossi, C N Hahn, S C Bray, P Neufing, W T Parker, J Feng, K Z Y Maung, A Wee, L Vidovic, C H Kok, P G Bardy, S Branford, I D Lewis, S W Lane, H S Scott, D M Ross, R J D'Andrea
We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2(V617F) Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFR(C329R) receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546756/new-developments-in-the-treatment-of-advanced-squamous-cell-lung-cancer-focus-on-afatinib
#2
REVIEW
Vera Hirsh
Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28542548/robustness-analysis-of-the-detailed-kinetic-model-of-an-erbb-signaling-network-by-using-dynamic-sensitivity
#3
Hiroyuki Masunaga, Yurie Sugimoto, Shigeyuki Magi, Ryunosuke Itasaki, Mariko Okada-Hatakeyama, Hiroyuki Kurata
The ErbB receptor signaling pathway plays an important role in the regulation of cellular proliferation, survival and differentiation, and dysregulation of the pathway is linked to various types of human cancer. Mathematical models have been developed as a practical complementary approach to deciphering the complexity of ErbB receptor signaling and elucidating how the pathways discriminate between ligands to induce different cell fates. In this study, we developed a simulator to accurately calculate the dynamic sensitivity of extracellular-signal-regulated kinase (ERK) activity (ERK*) and Akt activity (Akt*), downstream of the ErbB receptors stimulated with epidermal growth factor (EGF) and heregulin (HRG)...
2017: PloS One
https://www.readbyqxmd.com/read/28537922/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#4
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522156/the-role-of-erbb-receptors-in-infection
#5
REVIEW
Jemima Ho, David L Moyes, Mahvash Tavassoli, Julian R Naglik
Members of the epidermal growth factor receptor family (ErbB family) possess a wide distribution and diverse functions ranging from cellular growth to migration and apoptosis. Though highly implicated in a variety of cancers, their involvement in infectious disease is less recognised. A growing body of evidence now highlights the importance of the ErbB family in a variety of infections. Their role as growth factor receptors, along with other characteristics, such as surface expression and continuous intracellular trafficking, make this receptor family ideally placed for exploitation by pathogens...
May 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28521415/bioinformatics-analysis-of-dysregulated-micrornas-in-the-nipple-discharge-of-patients-with-breast-cancer
#6
Kai Zhang, Ya-Wen Wang, Rong Ma
MicroRNAs (miRNAs/miRs) have been reported to be associated with the tumorigenesis and progression of various types of human cancer; however, the underlying mechanisms of this association remain unclear. The aim of the present study was to explore the potential functions of miRNAs in the development of breast cancer using bioinformatics analysis, based on the miRNA expression profile in nipple discharge. A previous study demonstrated the upregulation of miR-3646 and miR-4484, and the downregulation of miR-4732-5p in the nipple discharge of patients with breast cancer, compared with patients with benign breast lesions...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521404/silencing-tak1-alters-gene-expression-signatures-in-bladder-cancer-cells
#7
Jimin Chen, Nan Zhang, Jiaming Wen, Zhewei Zhang
The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520590/role-of-tyrosine-kinase-inhibitors-in-the-treatment-of-pituitary-tumours-from-bench-to-bedside
#8
Anat Ben-Shlomo, Odelia Cooper
PURPOSE OF REVIEW: Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease...
May 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28507794/a-novel-nanobody-based-target-module-for-retargeting-of-t-lymphocytes-to-egfr-expressing-cancer-cells-via-the-modular-unicar-platform
#9
Susann Albert, Claudia Arndt, Anja Feldmann, Ralf Bergmann, Dominik Bachmann, Stefanie Koristka, Florian Ludwig, Pauline Ziller-Walter, Alexandra Kegler, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Marc Cartellieri, Gerhard Ehninger, Hans-Jürgen Pietzsch, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28498781/phase-i-study-and-biomarker-analysis-of-pyrotinib-a-novel-irreversible-pan-erbb-receptor-tyrosine-kinase-inhibitor-in-patients-with-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer
#10
Fei Ma, Qiao Li, Shanshan Chen, Wenjie Zhu, Ying Fan, Jiayu Wang, Yang Luo, Puyuan Xing, Bo Lan, Meiying Li, Zongbi Yi, Ruigang Cai, Peng Yuan, Pin Zhang, Qing Li, Binghe Xu
Purpose This phase I study assessed the safety, tolerability, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Patients and Methods Pyrotinib was administered continuously, orally, once per day to patients who did not have prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was 80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood samples were collected on day 1 and day 28...
May 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28492659/ensemble-clustering-of-phosphoproteomic-data-identifies-differences-in-protein-interactions-and-cell-cell-junction-integrity-of-her2-overexpressing-cells
#11
Katherine E Schaberg, Venktesh S Shirure, Elizabeth A Worley, Steven C George, Kristen M Naegle
Overexpression of HER2, a receptor tyrosine kinase of the ERBB family, in breast cancer is related to increased cancer progression and aggressiveness. A breast epithelial cell model with the single perturbation of HER2 overexpression is capable of replicating the increased aggressiveness of HER2 overexpressing cancers. In previous work, Wolf-Yadlin and colleagues (Wolf-Yadlin et al., Mol. Syst. Biol., 2006, 2) measured the proximal tyrosine phosphorylation dynamics of the parental and HER2 overexpressing cells (24H) in response to EGF...
May 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28485160/mir-34a-suppresses-hnscc-growth-through-modulating-cell-cycle-arrest-and-senescence
#12
Y Wang, J Chen, X Chen, F Jiang, Y Sun, Y Pan, W Zhang, J Zhang
MiR-34a acts as a tumor suppressor in various malignancies. In HNSCC, the role of miR-34a in proliferation has not been fully elaborated and the target genes are still bind. Here, we addressed that forced miR-34a expression induced cell cycle arrest and senescence. Hypoxia/HIF1α was found to negatively correlate to the expression of miR-34a in HNSCC tissues and partially reverse miR-34a-imposed cell senescence through suppressing miR-34a expression. In order to screen the possible target genes of miR-34a in HNSCC, the differential genes mediated by miR-34a were screened by mRNA microarray...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#13
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467812/a-subset-of-micrornas-defining-the-side-population-of-a-human-malignant-mesothelioma-cell-line
#14
Myung-Chul Kim, Na-Yon Kim, Yu-Ri Seo, Yongbaek Kim
This study was performed to investigate the global expression profile of microRNAs in distinct subpopulations of a human malignant mesothelioma cell line. Total RNAs were isolated from the sorted side population and non-side population of MS1. The RNAs were subjected to analysis using Affymetrix GeneChip microRNA Arrays. After data extraction and normalization, a subset of microRNAs defining cell subpopulations was identified using bioinformatics softwares. Based on the criteria of 2-fold difference and the p-value of < 0...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#15
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28440478/overexpression-of-secretory-phospholipase-a2-iia-supports-cancer-stem-cell-phenotype-via-her-erbb-elicited-signaling-in-lung-and-prostate-cancer-cells
#16
Shan Lu, Zhongyun Dong
Resistance to conventional chemotherapies remains a significant clinical challenge in treatment of cancer. The cancer stem cells (CSCs) have properties necessary for tumor initiation, resistance to therapy, and progression. HER/ERBB‑elicited signaling supports CSC properties. Our previous studies revealed that secretory phospholipase A2 group IIa (sPLA2‑IIa) is overexpressed in both prostate and lung cancer cells, leading to an aberrant high level in the interstitial fluid, i.e., tumor microenvironment and blood...
April 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#17
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28429830/establishment-and-evaluation-of-a-novel-biomarker-based-nomogram-for-malignant-phaeochromocytomas-and-paragangliomas
#18
Xu Zhong, Lei Ye, TingWei Su, Jing Xie, Weiwei Zhou, Yiran Jiang, Lei Jiang, Guang Ning, Weiqing Wang
OBJECTIVE: No single histological or molecular marker is diagnostic for malignant phaeochromocytomas and paragangliomas (PPGLs). This study aimed to establish and evaluate a prognostic nomogram to improve the prediction of metastatic probability in individual PPGL patients. METHODS: Three hundred and forty-seven consecutive PPGL patients from January 2002 through December 2014 were randomly divided into a training set (n=208) and a validation set (n=139). A multivariate logistic regression analysis of selected prognostic features was performed, and a nomogram to predict metastasis was constructed...
April 21, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28426879/acute-exposure-to-dehp-metabolite-mehp-cause-genotoxicity-mutagenesis-and-carcinogenicity-in-mammalian-chinese-hamster-ovary-cells
#19
Yu-Jung Chang, Chia-Yi Tseng, Pei-Ying Lin, Yu-Chen Chuang, Ming-Wei Chao
Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production of polyvinyl chloride, can be converted to the more potent metabolite mono-ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association with elevated induction of rat hepatic cancer and reproductive toxicity in response to MEHP exposure. However, the mechanism of genotoxicity and carcinogenicity induced by MEHP treatment remains unclear. As a means to elucidate the mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by MEHP were assessed...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#20
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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