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Epidermal growth factor receptor

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https://www.readbyqxmd.com/read/28650518/a-simple-in-silico-strategy-identifies-candidate-biomarkers-for-the-diagnosis-of-liver-fibrosis-in-morbidly-obese-subjects
#1
Pablo J Giraudi, Sabrina E Gambaro, Sofia Ornelas Arroyo, Carla M Chackelevicius, Michela Giuricin, Marta Silvestri, Daniele Macor, Lory S Crocé, Deborah Bonazza, Giorgio Soardo, Nicolò de Manzini, Fabrizio Zanconati, Claudio Tiribelli, Silvia Palmisano, Natalia Rosso
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis...
June 26, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28650473/testes-specific-protease-50-promotes-cell-proliferation-via-inhibiting-activin-signaling
#2
Z-B Song, P Wu, J-S Ni, T Liu, C Fan, Y-L Bao, Y Wu, L-G Sun, C-L Yu, Y-X Huang, Y-X Li
Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649895/the-safety-and-efficacy-of-palbociclib-in-the-treatment-of-metastatic-breast-cancer
#3
Johannes Ettl, Nadia Harbeck
Palbociclib (Ibrance(®)) is the first-in-class CDK4/6 inhibitor which has been introduced into clinical practice for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). It is an orally administered drug, which acts by selectively inhibiting cyclin-dependant kinases CDK4 and CDK6. Given together with anti-estrogens like letrozole and fulvestrant it enhances the antiproliferative effect of these drugs without compromising the favorable toxicity profile of endocrine therapy...
June 26, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28649658/niche-localized-tumor-cells-are-protected-from-her2-targeted-therapy-via-upregulation-of-an-anti-apoptotic-program-in-vivo
#4
Jason J Zoeller, Roderick T Bronson, Laura M Selfors, Gordon B Mills, Joan S Brugge
Several lines of evidence suggest that components of the tumor microenvironment, specifically basement membrane and extracellular matrix proteins, influence drug sensitivities. We previously reported differential drug sensitivity of tumor cells localized adjacent to laminin-rich extracellular matrix in three-dimensional tumor spheroid cultures. To evaluate whether differential intra-tumor responses to targeted therapy occur in vivo, we examined the sensitivity of human epidermal growth factor receptor 2-positive tumors to lapatinib using a previously described ductal carcinoma in situ-like model characterized by tumor cell confinement within ductal structures surrounded by an organized basement membrane...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649644/constitutional-variants-are-not-associated-with-her2-positive-breast-cancer-results-from-the-signal-phare-clinical-cohort
#5
Xavier Pivot, Gilles Romieu, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Cécile Agostini, Pierre Kerbrat, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Fabien Calvo, Alexia Renaud, Jean-François Deleuze, Iris Pauporté, Gilles Thomas, David G Cox
Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case-case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649410/komodo-dragon-inspired-synthetic-peptide-drgn-1-promotes-wound-healing-of-a-mixed-biofilm-infected-wound
#6
Ezra M C Chung, Scott N Dean, Crystal N Propst, Barney M Bishop, Monique L van Hoek
Cationic antimicrobial peptides are multifunctional molecules that have a high potential as therapeutic agents. We have identified a histone H1-derived peptide from the Komodo dragon (Varanus komodoensis), called VK25. Using this peptide as inspiration, we designed a synthetic peptide called DRGN-1. We evaluated the antimicrobial and anti-biofilm activity of both peptides against Pseudomonas aeruginosa and Staphylococcus aureus. DRGN-1, more than VK25, exhibited potent antimicrobial and anti-biofilm activity, and permeabilized bacterial membranes...
2017: NPJ Biofilms and Microbiomes
https://www.readbyqxmd.com/read/28648122/phase-1-study-to-investigate-the-pharmacokinetic-properties-of-dacomitinib-in-healthy-adult-chinese-subjects-genotyped-for-cyp2d6
#7
Xia Chen, Ji Jiang, Nagdeep Giri, Pei Hu
1. This study aimed to characterise the pharmacokinetics of dacomitinib, a pan-human epidermal growth factor receptor tyrosine kinase inhibitor, and its metabolite, PF-05199265, in healthy Chinese subjects. 2. In this open-label, single-centre, nonrandomised study (NCT02097433), 14 subjects received a single dacomitinib 45-mg oral dose. Pharmacokinetic samples for dacomitinib and PF-05199265 were collected pre- and postdose. Subjects were genotyped for cytochrome P450 (CYP)2D6 metaboliser status. Safety was assessed throughout the study...
June 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28647387/practical-considerations-for-the-use-of-breast-mri-for-breast-cancer-evaluation-in-the-preoperative-setting
#8
Debra L Monticciolo
Preoperative contrast-enhanced (CE) breast magnetic resonance imaging (MRI) remains controversial in the newly diagnosed breast cancer patient. Additional lesions are frequently discovered in these patients with CE breast MRI. As staging and treatment planning evolve to include more information on tumor biology and aggression, so should our consideration of extent of disease. Directing CE breast MRI to those patients most likely to have additional disease may be beneficial. We sought to develop practical guidance for the use of preoperative CE breast MRI in the newly diagnosed breast cancer patient based on recent scientific data...
June 21, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28646722/radiation-therapy-utilization-and-outcomes-for-older-women-with-breast-cancer-impact-of-molecular-subtype-and-tumor-grade
#9
Waqar Haque, Denley Ming Kee Yuan, Vivek Verma, E Brian Butler, Bin S Teh, Lee Wiederhold, Sandra Hatch
BACKGROUND: Radiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers. METHODS: The Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation...
June 21, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28646226/a-microrna-signature-of-response-to-erlotinib-is-descriptive-of-tgf%C3%AE-behaviour-in-nsclc
#10
Madeline Krentz Gober, James P Collard, Katherine Thompson, Esther P Black
Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645722/circulating-bone-related-markers-and-ykl-40-versus-her2-and-topo2a-in-bone-metastatic-and-nonmetastatic-breast-cancer-diagnostic-implications
#11
Olfat Gamil Shaker, Hebatullah Samy Helmy
BACKGROUND: The bone represents one of the most common sites of metastases in breast cancer. The aim of the current study was to evaluate the diagnostic potential of several circulating markers to detect metastasis to bones in patients with breast cancer. PATIENTS AND METHODS: Receptor activator of Nuclear Factor-kappa β (NF-Kβ) ligand (RANKL), osteoprotegrin (OPG), vitamin D (VIT D), Chitinase-3-like protein 1; also known as YKL-40, topoisomerase IIα (TOPO2a), and human epidermal growth factor receptor 2 (HER2) were measured in blood samples obtained from 122 patients with breast cancer and 25 healthy controls...
June 7, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28645631/outcomes-of-first-generation-egfr-tkis-against-non-small-cell-lung-cancer-harboring-uncommon-egfr-mutations-a-post-hoc-analysis-of-the-be-positive-study
#12
Sara Pilotto, Antonio Rossi, Tiziana Vavalà, Alessandro Follador, Marcello Tiseo, Domenico Galetta, Alessandro Morabito, Massimo Di Maio, Olga Martelli, Orazio Caffo, Pier Luigi Piovano, Diego Cortinovis, Nicoletta Zilembo, Clelia Casartelli, Giuseppe Luigi Banna, Antonio Ardizzoia, Maria Luisa Barzelloni, Alessandra Bearz, Giovenzio Genestreti, Claudia Mucciarini, Virginio Filipazzi, Jessica Menis, Elisa Rizzo, Fausto Barbieri, Erika Rijavec, Fabiana Cecere, Gianluca Spitaleri, Emilio Bria, Silvia Novello
BACKGROUND: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations...
June 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28644837/real-world-first-line-treatment-and-overall-survival-in-non-small-cell-lung-cancer-without-known-egfr-mutations-or-alk-rearrangements-in-us-community-oncology-setting
#13
Amy P Abernethy, Ashwini Arunachalam, Thomas Burke, Caroline McKay, Xiting Cao, Rachael Sorg, David P Carbone
PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015)...
2017: PloS One
https://www.readbyqxmd.com/read/28644615/fluoromodules-consisting-of-a-promiscuous-rna-aptamer-and-red-or-blue-fluorogenic-cyanine-dyes-selection-characterization-and-bioimaging
#14
Xiaohong Tan, Tudor P Constantin, Kelly L Sloane, Alan S Waggoner, Marcel P Bruchez, Bruce A Armitage
An RNA aptamer selected for binding to the fluorogenic cyanine dye, dimethylindole red (DIR), also binds and activates another cyanine, oxazole thiazole blue (OTB), giving two well-resolved emission colors. The aptamer binds to each dye with submicromolar KD values, and the resulting fluoromodules exhibit fluorescence quantum yields ranging from 0.17 to 0.51 and excellent photostability. The aptamer was fused to a second aptamer previously selected for binding to the epidermal growth factor receptor (EGFR) to create a bifunctional aptamer that labels cell-surface EGFR on mammalian cells...
June 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28643145/the-prognostic-value-of-volume-based-parameters-using-18-f-fdg-pet-ct-in-gastric-cancer-according-to-her2-status
#15
Ji Soo Park, Nare Lee, Seung Hoon Beom, Hyo Song Kim, Choong-Kun Lee, Sun Young Rha, Hyun Cheol Chung, Mijin Yun, Arthur Cho, Minkyu Jung
BACKGROUND: We aimed to find the clinical value of metastatic tumor burden evaluated with F18-FDG PET/CT in gastric cancer patients, considering the human epidermal growth factor receptor 2 (HER2) status. METHODS: We retrospectively reviewed 124 patients with locally advanced or metastatic gastric cancer at Yonsei Cancer Center between January 2006 and December 2014 who had undergone baseline FDG PET/CT before first-line chemotherapy. We measured the maximum standardized uptake value from the primary tumor (SUVmax) and whole-body (WB) PET/CT parameters, including WB SUVmax, WB SUVmean, WB metabolic tumor volume (WB MTV), and WB total lesion glycolysis (WB TLG), in all metabolically active metastatic lesions (SUV threshold ≥2...
June 22, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28643125/the-role-of-prmt1-in-egfr-methylation-and-signaling-in-mda-mb-468-triple-negative-breast-cancer-cells
#16
Katsuya Nakai, Weiya Xia, Hsin-Wei Liao, Mitsue Saito, Mien-Chie Hung, Hirohito Yamaguchi
BACKGROUND: Epidermal growth factor receptor (EGFR) is often overexpressed in triple-negative breast cancer (TNBC). However, clinical studies have shown that therapies against EGFR are not effective in patients with TNBC. Recently, it has been reported that arginine 198/200 in EGFR extracellular domain is methylated by PRMT1 and that the methylation confers resistance to EGFR monoclonal antibody cetuximab in colorectal cancer cells. To explore a potential mechanism underlying intrinsic resistance to anti-EGFR therapy in TNBC, we investigated the role of PRMT1 in EGFR methylation and signaling in MDA-MB-468 (468) TNBC cells...
June 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28642830/a-rare-case-of-esophageal-adenocarcinoma-with-urinary-bladder-metastasis
#17
Heather Katz, Rahoma E Saad, Krista Denning, Toni O Pacioles
Metastatic esophageal adenocarcinoma to the urinary bladder is extremely rare. We describe a previously healthy 49-year-old female with recent diagnosis of adenocarcinoma of the gastroesophageal junction with metastatic disease to the liver. Biopsy was positive for human epidermal growth factor receptor 2 (HER2) by Fluorescence In Situ Hybridization (FISH). She received six cycles of Cisplatin, 5-Fluorouracil, and Herceptin and subsequently developed symptomatic anemia and hematuria. Cystoscopy with retroflexion was performed and she received a transurethral resection of bladder tumor with fulguration...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/28642617/podoplanin-enhances-lung-cancer-cell-growth-in-vivo-by-inducing-platelet-aggregation
#18
Kenichi Miyata, Ai Takemoto, Sakae Okumura, Makoto Nishio, Naoya Fujita
Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642172/egfr-t790m-ctdna-testing-platforms-and-their-role-as-companion-diagnostics-correlation-with-clinical-outcomes-to-egfr-tkis
#19
Zhiyong Liang, Ying Cheng, Yuan Chen, Yanping Hu, Wei-Ping Liu, You Lu, Jie Wang, Ye Wang, Gang Wu, Jian-Ming Ying, He-Long Zhang, Xu-Chao Zhang, Yi-Long Wu
Somatic mutation in the epidermal growth factor receptor (EGFR) predict clinical response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) and is a promising target for personalised medicine. EGFR mutations have prognostic value. Initially patients respond well to tyrosine kinase inhibitors but finally they would develop resistance and about 50% of this resistance can be attributed to the emergence of EGFR resistant mutation, T790M. This necessitates the need for genetic testing for clinical management of patients...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28642126/molecular-and-hydrodynamic-properties-of-human-epidermal-growth-factor-receptor-her2-extracellular-domain-and-its-homodimer-experiments-and-multi-scale-simulations
#20
J F Vega, J Ramos, V Cruz, E Vicente-Alique, E Sánchez-Sánchez, A Sánchez-Fernández, Y Wang, P Hu, J Cortés, J Martínez-Salazar
BACKGROUND: In a broad range of human carcinomas gene amplification leads to HER2 overexpression, which has been proposed to cause spontaneous dimerization and activation in the absence of ligand. This makes HER2 attractive as a therapeutic target. However, the HER2 homodimerization mechanism remains unexplored. It has been suggested that the "back-to-back" homodimer does not form in solution. Notwithstanding, very recently the crystal structure of the HER2 extracellular domain homodimer formed with a "back-to-head" interaction has been resolved...
June 19, 2017: Biochimica et Biophysica Acta
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