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Epithelial growth factor receptor

Tobias Wiedemann, Stefan Hofbaur, Eva Loell, Gabriele Rieder
Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H...
September 29, 2016: European Journal of Microbiology & Immunology
Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
Sapna M Amin, Adam Beattie, Xia Ling, Lawrence J Jennings, Joan Guitart
Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female...
November 2016: American Journal of Dermatopathology
Francesca Bianchini, Silvia Peppicelli, Pierangelo Fabbrizzi, Alessio Biagioni, Benedetta Mazzanti, Gloria Menchi, Lido Calorini, Alberto Pupi, Andrea Trabocchi
Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident...
October 19, 2016: Molecular and Cellular Biochemistry
Kevin K Kim, Thomas H Sisson, Jeffrey C Horowitz
Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells and macrophages responding to an array of soluble and matrix mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF and PDGF receptors can slow the rate of decline in pulmonary function in patients with idiopathic pulmonary fibrosis. However, each of these growth factor families is comprised of multiple ligands and receptors with pleiotropic activities on different cell types such that their broad inhibition might have both pro-fibrotic and anti-fibrotic effects, limiting the potential therapeutic efficacy...
October 19, 2016: Journal of Pathology
James Scholey
The classical view of the RAS is a linear signaling pathway beginning with the conversion of angiotensinogen to ANG I by renin, an enzyme secreted by the kidney. ANG I is converted to ANG II by angiotensin converting enzyme (ACE) ANG II binds to the G-protein coupled angiotensin II receptor type 1. The RAS is a circulating system but we now know that the RAS is also locally expressed in a number of tissues, including the kidneys and the heart. ANG II exerts adverse hemodynamic and non-hemodynamic effects on renal cells...
September 2016: Journal of Hypertension
Marta Mikolajczak, Timothy Goodman, Mohammad K Hajihosseini
Heterozygous mutations in the gene encoding fibroblast growth factor 10 (FGF10) or its cognate receptor, FGF-receptor 2 IIIb (FGFR2-IIIb) result in two human syndromes - LADD (lacrimo-auriculo-dento-digital) and ALSG (Aplasia of lacrimal and salivary glands). To date, the partial loss-of-FGF10 function in these patients has been attributed solely to perturbed paracrine signalling functions between FGF10-producing mesenchymal cells and FGF10-responsive epithelial cells. However, the functioning of a LADD-causing G138E FGF10 mutation, which falls outside its receptor interaction interface, has remained enigmatic...
October 14, 2016: Biochemical Journal
Shiho Sugawara, Masahiko Maeno, Cliff Lee, Shigemi Nagai, David M Kim, John Da Silva, Masazumi Nagai, Hisatomo Kondo
The aim of this study was to produce epithelial attachment on a typical implant abutment surface of smooth titanium. A challenging complication that hinders the success of dental implants is peri-implantitis. A common cause of peri-implantitis may results from the lack of epithelial sealing at the peri-implant collar. Histologically, epithelial sealing is recognized as the attachment of the basement membrane (BM). BM-attachment is promoted by activated platelet aggregates at surgical wound sites. On the other hand, platelets did not aggregate on smooth titanium, the surface typical of the implant abutment...
2016: PloS One
Chongxiang Xiong, Monica V Masucci, Xiaoxu Zhou, Na Liu, Xiujuan Zang, Evelyn Tolbert, Ting C Zhao, Shougang Zhuang
Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively inhibit tumorgenesis and ameliorate pulmonary fibrosis by targeting bromodomain proteins that bind acetylated chromatin markers. However, their pharmacological effects in renal fibrosis remain unclear. In this study, we examined the effect of I-BET151, a selective and potent BET inhibitor, on renal fibroblast activation and renal fibrosis. In cultured renal interstitial fibroblasts, exposure of cells to I-BET151, or silencing of bromodoma in-containing protein 4 (Brd4), a key BET protein isoform, significantly reduced their activation as indicated by decreased expression of α-smooth muscle actin, collagen 1 and fibronectin...
October 6, 2016: Oncotarget
Ping Zhan, Xiao Chen, Xiao-Yuan Wu, Zhi-Bo Hou, Qian Qian, Yu Zhang, Jue Zou, Yuan-Qing Zhang, Ming-Yue Wan, Jian-Dong Wang, Li-Ke Yu, Hai-Yan Xie
INTRODUCTION: For thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years. OBJECTIVES: Mutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti-EGFR therapies. METHODS: Genomic DNA was extracted from 61 histological samples of TCs...
October 12, 2016: Clinical Respiratory Journal
Winifred Broekman, Helene Roelofs, Maria C Zarcone, Christian Taube, Jan Stolk, Pieter S Hiemstra
Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated for clinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPD affects BM-MSCs. To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls were compared with regard to immunophenotype, growth and differentiation potential, and migration capacity. Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclear factor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCI-H292 airway epithelial cells...
April 2016: ERJ Open Research
Jin Young Kim, Garam Kim, Sung-Chul Lim, Hong Seok Choi
LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways...
October 11, 2016: Carcinogenesis
Duncan Hieu M Dam, Xiao-Qi Wang, Sarah Sheu, Mahima Vijay, Desmond Shipp, Luke Miller, Amy S Paller
Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling induces keratinocyte migration, but little is known about its regulation, including in diabetic wounds. GM3, a lipid raft ganglioside synthesized by GM3 synthase (GM3S), regulates receptor signaling. In diabetic mice, knockout or topically-applied nanoconstruct-mediated knockdown of GM3S promotes wound edge IGF1R phosphorylation and re-epithelialization. Through modulating GM3 expression, we explored the role of GM3 in regulating human keratinocyte IGF1R signaling...
October 8, 2016: Journal of Investigative Dermatology
Susanne Muehlich, Margot Rehm, Astrid Ebenau, Margarete Goppelt-Struebe
Changes in cell morphology that involve alterations of the actin cytoskeleton are a hallmark of diseased renal tubular epithelial cells. While the impact of actin remodeling on gene expression has been analyzed in many model systems based on cell lines, this study investigated human primary tubular epithelial cells isolated from healthy parts of tumor nephrectomies. Latrunculin B (LatB) and cytochalasin D (CytoD) were used to modulate G-actin levels in a receptor-independent manner. Both compounds (at 0.5μM) profoundly altered F-actin structures in a Rho kinase-dependent manner, but only CytoD strongly induced the pro-fibrotic factor CTGF (connective tissue growth factor)...
October 7, 2016: Cellular Signalling
Natalie K Binder, Jemma Evans, Lois A Salamonsen, David K Gardner, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan
Embryo implantation requires synchronized dialogue between the receptive endometrium and activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle, increased glandular secretion into the uterine lumen provides important mediators that modulate the endometrium and support the conceptus during implantation. Previously we demonstrated the importance of vascular endothelial growth factor (VEGF) in the human uterus, particularly with respect to embryo implantation...
2016: PloS One
Ana Vila, Miguel Abal, Laura Muinelo-Romay, Carlos Rodriguez-Abreu, José Rivas, Rafael López-López, Clotilde Costa
Circulating tumour cells (CTCs) play a key role in the metastasis process, as they are responsible for micrometastasis and are a valuable tool for monitoring patients in real-time. Moreover, efforts to develop new strategies for CTCs isolation and characterisation, and the translation of CTCs into clinical practice needs to overcome the limitation associated with the sole use of Epithelial Cell Adhesion Molecule (EpCAM) expression to purify this tumour cell subpopulation. CTCs are rare events in the blood of patients and are believed to represent the epithelial population from a primary tumour of epithelial origin, thus EpCAM immunoisolation is considered an appropriate strategy...
2016: PloS One
Hye-Young Min, Hye-Jin Boo, Ho Jin Lee, Hyun-Ji Jang, Hye Jeong Yun, Su Jung Hwang, John Kendal Smith, Hyo-Jong Lee, Ho-Young Lee
Activation of receptor tyrosine kinases (RTKs) is associated with carcinogenesis, but its contribution to smoking-associated lung carcinogenesis is poorly understood. Here we show that a tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced insulin-like growth factor 1 receptor (IGF-1R) activation via β-adrenergic receptor (β-AR) is crucial for smoking-associated lung carcinogenesis. Treatment with NNK stimulated the IGF-1R signaling pathway in a time- and dose-dependent manner, which was suppressed by pharmacological or genomic blockade of β-AR and the downstream signaling including a Gβγ subunit of β-AR and phospholipase C (PLC)...
September 29, 2016: Oncotarget
Joseph W Sassani, Patricia J Mc Laughlin, Ian S Zagon
The Opioid Growth Regulatory System consists of opioid growth factor (OGF), [Met(5)]-enkephalin, and its unique receptor (OGFr). OGF inhibits cell division when bound to OGFr. Conversely, blockade of the interaction of OGF and OGFr, using the potent, long-acting opioid receptor antagonist, naltrexone (NTX), results in increased DNA synthesis and cell division. The authors have demonstrated both in vitro and in vivo that the addition of exogenous OGF or an increase in available OGFr decreases corneal epithelial cell division and wound healing...
2016: Journal of Diabetes Research
Jane Antony, Tuan Zea Tan, Zoe Kelly, Jeffrey Low, Mahesh Choolani, Chiara Recchi, Hani Gabra, Jean Paul Thiery, Ruby Yun-Ju Huang
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines...
October 4, 2016: Science Signaling
Fernanda Silva, Ana Félix, Jacinta Serpa
Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages...
October 2016: Oncology Letters
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