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https://www.readbyqxmd.com/read/27902463/novel-multi-targeted-erbb-family-inhibitor-afatinib-blocks-egf-induced-signaling-and-induces-apoptosis-in-neuroblastoma
#1
Xinfang Mao, Zhenghu Chen, Yanling Zhao, Yang Yu, Shan Guan, Sarah E Woodfield, Sanjeev A Vasudevan, Ling Tao, Jonathan C Pang, Jiaxiong Lu, Huiyuan Zhang, Fuchun Zhang, Jianhua Yang
Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895758/metaplastic-carcinoma-of-the-breast-imaging-and-pathological-features
#2
Tiantian Bian, Qing Lin, Zengjie Wu, Chunxiao Cui, Chunhua Qi, Li Li, Xiaohui Su
Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of the present study was to investigate the imaging and pathological features of metaplastic carcinoma. The features identified on mammography and sonography were retrospectively reviewed in 13 women with metaplastic carcinoma of the breast. The results from the mammographs and sonographs were additionally evaluated using immunohistochemical staining for the expression of the estrogen receptor (ER) and progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (CerbB-2) and P53...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895658/overexpression-of-a-hevea-brasiliensis-erbb-3-binding-protein-1-gene-increases-drought-tolerance-and-organ-size-in-arabidopsis
#3
Han Cheng, Xiang Chen, Jianshun Zhu, Huasun Huang
Rubber trees are economically important tropical tree species and the major source of natural rubber, which is an essential industrial material. This tropical perennial tree is susceptible to cold stress and other abiotic stresses, especially in the marginal northern tropics. Recent years, the genome sequencing and RNA-seq projects produced huge amount of sequence data, which greatly facilitated the functional genomics study. However, the characterization of individual functional gene is in urgent demands, especially for those involved in stress resistance...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27893711/the-induction-of-mig6-under-hypoxic-conditions-is-critical-for-dormancy-in-primary-cultured-lung-cancer-cells-with-activating-egfr-mutations
#4
H Endo, J Okami, H Okuyama, Y Nishizawa, F Imamura, M Inoue
The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27888826/clinical-significance-of-ki-67-c-erbb-2-and-e-cadherin-expressions-in-open-partial-laryngectomy-patients
#5
Ozan Barutçu, Medine Kara, Aslı Muratlı, Oğuz Güçlü, Sefa Dereköy
OBJECTIVES: This study aims to analyze the correlation between biomarkers and risks of cervical lymph node invasion, recurrence, distant metastasis and survival regarding the clinicopathological variables in laryngeal cancers. PATIENTS AND METHODS: Forty-one patients with laryngeal cancers were examined retrospectively. The correlations evaluated between E-cadherin, Ki-67, c-erbB-2 expressions, tumor site, differentiation, the risk of cervical lymph node metastasis, perineural, perivascular, pericapsular invasion and recurrence as well as survival time...
September 2016: Kulak Burun Boğaz Ihtisas Dergisi: KBB, Journal of Ear, Nose, and Throat
https://www.readbyqxmd.com/read/27873136/afatinib-a-review-in-advanced-non-small-cell-lung-cancer
#6
REVIEW
Gillian M Keating
Afatinib (Giotrif(®), Gilotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial)...
November 22, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27872953/a-phase-i-study-of-afatinib-combined-with-paclitaxel-and-bevacizumab-in-patients-with-advanced-solid-tumors
#7
James Spicer, Sheeba Irshad, Joo Ern Ang, Deborah Enting, Rebecca Kristeleit, Martina Uttenreuther-Fischer, Karine Pemberton, Katy Pelling, David Schnell, Johann de Bono
PURPOSE: The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors. METHODS: This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed. The starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel (fixed dose 80 mg/m(2), Days 1, 8, and 15 of a 4-week cycle) and intravenous bevacizumab 5 mg/kg every 2 weeks...
November 21, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27872189/biophysical-evidence-for-intrinsic-disorder-in-the-c-terminal-tails-of-the-egfr-and-her3-receptor-tyrosine-kinases
#8
Theodore R Keppel, Kwabena Sarpong, Elisa M Murray, John Monsey, Jian Zhu, Ron Bose
The EGFR/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine if these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails to the ordered kinase domains...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27866247/identification-of-potential-peripheral-blood-diagnostic-biomarkers-for-patients-with-juvenile-idiopathic-arthritis-by-bioinformatics-analysis
#9
Zhi-Qiang Tu, Hai-Yan Xue, Wei Chen, Lan-Fang Cao, Wei-Qi Zhang
Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming children health. However, there is still lack of effective biomarkers for diagnosis JIA at early onset. We aim to construct a classification model to predict JIA disease. The peripheral blood gene expression profile data of JIA were downloaded from GEO database. We compared and analyzed differentially expressed genes (DEGs) between different JIA samples through Pearson's correlation coefficient method and unsupervised clustering analysis...
November 19, 2016: Rheumatology International
https://www.readbyqxmd.com/read/27861634/molecular-characterization-of-striated-muscle-specific-gab1-isoform-as-a-critical-signal-transducer-for-neuregulin-1-erbb-signaling-in-cardiomyocytes
#10
Taku Yasui, Takeshi Masaki, Yoh Arita, Tomohiko Ishibashi, Tadakatsu Inagaki, Makoto Okazawa, Toru Oka, Wataru Shioyama, Keiko Yamauchi-Takihara, Issei Komuro, Yasushi Sakata, Yoshikazu Nakaoka
Grb2-associated binder (Gab) docking proteins regulate signals downstream of a variety of growth factors and receptor tyrosine kinases. Neuregulin-1 (NRG-1), a member of epidermal growth factor family, plays a critical role for cardiomyocyte proliferation and prevention of heart failure via ErbB receptors. We previously reported that Gab1 and Gab2 in the myocardium are essential for maintenance of myocardial function in the postnatal heart via transmission of NRG-1/ErbB-signaling through analysis of Gab1/Gab2 cardiomyocyte-specific double knockout mice...
2016: PloS One
https://www.readbyqxmd.com/read/27856207/relationship-between-primary-tumour-18-f-fdg-uptake-and-immunohistochemical-and-clinical-prognostic-parameters-in-breast-carcinoma
#11
G K Gedik, F Yilmaz, O Sari
OBJECTIVE: The objective of this study was to investigate the relationship between level of (18)F-fluorodeoxyglucose ((18)F-FDG) accumulation in primary breast tumour assessed by positron emission tomography/computed tomography (PET/CT) and histopathological and clinical prognostic factors. MATERIAL AND METHODS: A retrospective analysis was performed using the medical records of 58 female patients (age range: 31-86 years, mean age: 56) with biopsy of proven breast carcinoma, and who had undergone (18)F-FDG PET/CT examination before chemotherapy/surgery...
November 14, 2016: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/27833557/immune-responses-to-epidermal-growth-factor-receptor-egfr-and-their-application-for-cancer-treatment
#12
REVIEW
Tetsuro Sasada, Koichi Azuma, Junya Ohtake, Yuki Fujimoto
Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27819121/analysis-of-the-interplay-between-methylation-and-expression-reveals-its-potential-role-in-cancer-aetiology
#13
Bugra Ozer, Ugur Sezerman
With ongoing developments in technology, changes in DNA methylation levels have become prevalent to study cancer biology. Previous studies report that DNA methylation affects gene expression in a direct manner, most probably by blocking gene regulatory regions. In this study, we have studied the interplay between methylation and expression to improve our knowledge of cancer aetiology. For this purpose, we have investigated which genomic regions are of higher importance; hence, first exon, 5'UTR and 200 bp near the transcription start sites are proposed as being more crucial compared to other genomic regions...
November 7, 2016: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/27813589/influence-of-chitosan-nanoparticle-mediated-c-erbb-2-gene-silencing-on-invasion-and-apoptosis-of-hep-2-cells
#14
W R Liu, L R Cao, G J Zuo
We aimed to measure the invasion ability of Hep-2 laryngeal cancer cells after treatment with C-erbB-2-small interfering RNA (siRNA)-chitosan nanoparticles, and assess the applied value of chitosan nanoparticle-mediated C-erbB-2 interference in inhibiting laryngeal cancer invasion and metastasis. Nanoparticles of approximately 100 nm, comprising C-erbB-2 siRNA packaged with chitosan, were prepared and used to treat Hep-2 cells. Silencing of C-erbB-2 was detected by western blot and polymerase chain reaction...
October 17, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27787847/characterizing-erbb-2-mediated-tyrosine-phosphorylation-and-activation-of-plexins
#15
Thomas Worzfeld, Jakub M Swiercz
Plexins comprise a family of transmembrane receptors for semaphorins. Plexins of the B- and D-subfamily interact with the receptor tyrosine kinase ErbB-2, and this interaction has been shown to be functionally relevant for various biological processes including tumor metastasis and bone formation. Binding of semaphorins to B- and D-subfamily plexins results in the activation of ErbB-2, which in turn phosphorylates these plexins. This phosphorylation triggers the activation of the small GTPases RhoA and RhoC downstream of B-subfamily plexins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27782124/wnt-and-neuregulin1-erbb-signalling-extends-3d-culture-of-hormone-responsive-mammary-organoids
#16
Thierry Jardé, Bethan Lloyd-Lewis, Mairian Thomas, Howard Kendrick, Lorenzo Melchor, Lauriane Bougaret, Peter D Watson, Kenneth Ewan, Matthew J Smalley, Trevor C Dale
The development of in vitro culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation ex vivo in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland in vivo...
October 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27776352/the-impact-of-erbb-family-germline-single-nucleotide-polymorphisms-on-survival-response-to-adjuvant-trastuzumab-treatment-in-her2-positive-breast-cancer
#17
Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27775071/extracellular-region-of-epidermal-growth-factor-receptor-a-potential-target-for-anti-egfr-drug-discovery
#18
A Dokala, S S Thakur
The epidermal growth factor receptor (EGFR) is a transmembrane receptor with tyrosine kinase activity involved in regulation of cellular multiplication, survival, differentiation and metastasis. Our knowledge about function and complex management of these receptors has driving the development of specific and targeted treatment modalities for human cancers in the last 20 years. EGFR is the first receptor target against which monoclonal antibodies (mAb) have been evolved for cancer treatment. Here we review the biology of ErbB receptors, including their architecture, signaling, regulation and therapeutic strategies and the mechanisms of resistances offered by the receptors against small-molecule tyrosine kinases and resistance overcome implications of mAbs...
October 24, 2016: Oncogene
https://www.readbyqxmd.com/read/27775011/the-dipole-potential-modifies-the-clustering-and-ligand-binding-affinity-of-erbb-proteins-and-their-signaling-efficiency
#19
Tamás Kovács, Gyula Batta, Tímea Hajdu, Ágnes Szabó, Tímea Váradi, Florina Zákány, István Csomós, János Szöllősi, Peter Nagy
Although activation of the ErbB family of receptor tyrosine kinases (ErbB1-4) is driven by oligomerization mediated by intermolecular interactions between the extracellular, the kinase and the transmembrane domains, the transmembrane domain has been largely neglected in this regard. The largest contributor to the intramembrane electric field, the dipole potential, alters the conformation of transmembrane peptides, but its effect on ErbB proteins is unknown. Here, we show by Förster resonance energy transfer (FRET) and number and brightness (N&B) experiments that the epidermal growth factor (EGF)-induced increase in the homoassociation of ErbB1 and ErbB2 and their heteroassociation are augmented by increasing the dipole potential...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27766079/restoring-lost-anti-her-2-th1-immunity-in-breast-cancer-a-crucial-role-for-th1-cytokines-in-therapy-and-prevention
#20
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
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