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HER2 amplification

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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
#1
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
https://www.readbyqxmd.com/read/28637432/current-guidelines-for-brca-testing-of-breast-cancer-patients-are-insufficient-to-detect-all-mutation-carriers
#2
Eli Marie Grindedal, Cecilie Heramb, Inga Karsrud, Sarah Louise Ariansen, Lovise Mæhle, Dag Erik Undlien, Jan Norum, Ellen Schlichting
BACKGROUND: Identification of BRCA mutations in breast cancer (BC) patients influences treatment and survival and may be of importance for their relatives. Testing is often restricted to women fulfilling high-risk criteria. However, there is limited knowledge of the sensitivity of such a strategy, and of the clinical aspects of BC caused by BRCA mutations in less selected BC cohorts. The aim of this report was to address these issues by evaluating the results of BRCA testing of BC patients in South-Eastern Norway...
June 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28625044/her2-status-and-its-heterogeneity-in-gastric-carcinoma-of-vietnamese-patients
#3
Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen
Background: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. Materials and Methods: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH...
June 19, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#4
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
June 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28611940/involvement-of-chromatin-remodeling-genes-and-the-rho-gtpases-rhob-and-cdc42-in-ovarian-clear-cell-carcinoma
#5
Nicolai Skovbjerg Arildsen, Jenny-Maria Jönsson, Katarina Bartuma, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid A Hedenfalk
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28599900/clinicopathologic-and-molecular-markers-in-cervical-carcinoma-a-prospective-cohort-study
#6
Mari Kyllesø Halle, Akinyemi I Ojesina, Hilde Engerud, Kathrine Woie, Ingvild Løberg Tangen, Frederik Holst, Erling Høivik, Kanthida Kusonmano, Ingfrid S Haldorsen, Olav K Vintermyr, Jone Trovik, Bjørn I Bertelsen, Helga B Salvesen, Camilla Krakstad
BACKGROUND: Cervical cancer is a major health problem worldwide. Identification of effective clinicopathologic and molecular markers is vital to improve treatment stratification. OBJECTIVES: To validate a set of well-defined clinicopathologic features in a large population based, prospectively collected cervical cancer cohort to support their use in the clinic. Further, we explore p53 and HER2 as potential prognostic markers in cervical cancer. STUDY DESIGN: Tissue was collected from 401 cervical cancer patients...
June 6, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28599421/age-associated-prognostic-and-predictive-biomarkers-in-patients-with-breast-cancer
#7
Markéta Kolečková, Zdeněk Kolář, Jiří Ehrmann, Gabriela Kořínková, Radek Trojanec
To date, no comprehensive prognostic or predictive marker profiling analysis has been performed in association with the age of patients with breast cancer. In the present study, 632 breast cancer tissue samples were analyzed for expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), B-cell lymphoma (Bcl)-2 protein, HER2 gene amplification, proliferation [as evaluated by proliferating cell nuclear antigen (PCNA) and Ki-67 index], tumor grade, histological type and molecular subtype...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596498/somatic-mutations-in-salivary-duct-carcinoma-and-potential-therapeutic-targets
#8
Timothy K Khoo, Bing Yu, Joel A Smith, Angus J Clarke, Peter P Luk, Christina I Selinger, Kate L Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J Boyer, Marcel E Dinger, Mark J Cowley, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
BACKGROUND: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. RESULTS: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573357/clinical-significance-of-overexpression-of-nrg1-and-its-receptors-her3-and-her4-in-gastric-cancer-patients
#9
Sumi Yun, Jiwon Koh, Soo Kyung Nam, Jung Ok Park, Sung Mi Lee, Kyoungyul Lee, Kyu Sang Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
BACKGROUND: Neuregulin 1 (NRG1), a ligand for human epidermal growth factor (HER) 3 and HER4, can activates cell signaling pathways to promote carcinogenesis and metastasis. METHODS: To investigate the clinicopathologic significance of NRG1 and its receptors, immunohistochemistry was performed for NRG1, HER3, and HER4 in 502 consecutive gastric cancers (GCs). Furthermore, HER2, microsatellite instability (MSI), and Epstein-Barr virus (EBV) status were investigated...
June 1, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28571140/her2-neu-testing-in-432-consecutive-breast-cancer-cases-using-fish-and-ihc-a-comparative-study
#10
Venkataswamy Eswarachary, Imran Gorur Mohammed, Prashanth K Jayanna, Geeta V Patilokaly, Ashwini R Nargund, Gopal Krishna Dhondalay, Shilpa Prabhudesai, Rashmita Sahoo
INTRODUCTION: The development of trastuzumab, a HER-2/neu targeted monoclonal antibody resulted in significant improvements in clinical response and survival in HER-2/neu gene amplified group of patients. Thus, accurate assessment of HER-2/neu status becomes critical. Fluorescence In Situ Hybridization (FISH) and Immunohistochemistry (IHC) are the most commonly used methods for this purpose and specific recommendations exist with regard to the concordance to be observed between the two tests...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28567637/comparison-of-her2-amplification-status-among-breast-cancer-subgroups-offers-new-insights-in-pathways-of-breast-cancer-progression
#11
Kathleen Lambein, Mieke Van Bockstal, Lies Vandemaele, Rudy Van den Broecke, Veronique Cocquyt, Sofie Geenen, Hannelore Denys, Louis Libbrecht
Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC...
May 31, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28554745/genomic-profiling-of-esophageal-squamous-cell-carcinoma-escc-basis-for-precision-medicine
#12
Jung Wook Yang, Yoon-La Choi
PURPOSE: Preparing for precision medicine, we surveyed genomic alterations in esophageal squamous cell carcinoma (ESCC) and identified candidate therapeutic targets by genomic profiling using next-generation sequencing (NGS). MATERIALS AND METHODS: Single-nucleotide variations, indels, and copy number variations in 80 genes were evaluated by targeted deep sequencing in 24 surgically resected ESCC specimens. Immunohistochemistry analyses and silver in situ hybridization for ERBB2 (HER2) were conducted to verify the NGS results...
February 28, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28536037/identification-of-molecular-targets-in-vulvar-cancers
#13
Marguerite L Palisoul, Mary M Mullen, Rebecca Feldman, Premal H Thaker
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH)...
May 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28523293/-triple-positive-breast-cancer-a-novel-category
#14
George Iancu, DănuŢ Vasile, Raluca Claudia Iancu, Dragoş Virgil DaviŢoiu
Breast cancer (BC) biology is of outmost importance for its therapeutic management and for establishing patients' outcome. Breast cancer has been divided in subtypes depending on the presence of hormone receptors (HRs) for estrogen and progesterone and human epidermal growth factor receptor 2 (HER2) gene amplification. Recently, a distinct subcategory has been analyzed from the group of HER2-enriched BC with positive HR, namely HER2 positive with high levels of hormone receptor expression, suggestively named "triple positive" breast cancer...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28508152/detection-of-her2-amplification-in-circulating-tumor-cells-of-her2-negative-gastric-cancer-patients
#15
Yuji Mishima, Satoshi Matsusaka, Keisho Chin, Mariko Mikuniya, Sayuri Minowa, Tomoko Takayama, Harumi Shibata, Ryoko Kuniyoshi, Mariko Ogura, Yasuhito Terui, Nobuyuki Mizunuma, Kiyohiko Hatake
A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient's malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs)...
May 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28502100/her2-fish-results-in-breast-cancers-with-increased-cen17-signals-using-alternative-chromosome-17-probes-reclassifying-cases-in-the-equivocal-category
#16
Maria-Anna Holzschuh, Zbigniew Czyz, Sven Hauke, Elisabeth Christine Inwald, Bernhard Polzer, Gero Brockhoff
AIMS: HER2 testing of invasive breast cancer by in-situ hybridisation guides therapy decisions. Probing HER2 and cen17 simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered "equivocal" which is diagnostically meaningless. Moreover, patients with equivocal / false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122, and TP53 hybridisation markers to reliably indicate true polysomy and to accurately reclassify equivocal samples as HER2-positive...
May 14, 2017: Histopathology
https://www.readbyqxmd.com/read/28501091/update-on-gastroesophageal-adenocarcinoma-targeted-therapies
#17
REVIEW
Steven B Maron, Daniel V T Catenacci
Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the metastatic setting as GEC. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date-only first-line anti-HER2 therapy for ERBB2 amplification and second-line anti-VEGFR2 therapy...
June 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28493933/direct-estrogen-receptor-er-her-family-crosstalk-mediating-sensitivity-to-lumretuzumab-and-pertuzumab-in-er-breast-cancer
#18
Denis Collins, Wolfgang Jacob, Juan Miguel Cejalvo, Maurizio Ceppi, Ian James, Max Hasmann, John Crown, Andrés Cervantes, Martin Weisser, Birgit Bossenmaier
Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#19
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)...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460632/her2-assessment-using-quantitative-reverse-transcriptase-polymerase-chain-reaction-reliably-identifies-her2-overexpression-without-amplification-in-breast-cancer-cases
#20
Gabriele Zoppoli, Anna Garuti, Gabriella Cirmena, Ludovica Verdun di Cantogno, Cristina Botta, Maurizio Gallo, Domenico Ferraioli, Enrico Carminati, Paola Baccini, Monica Curto, Piero Fregatti, Edoardo Isnaldi, Michela Lia, Roberto Murialdo, Daniele Friedman, Anna Sapino, Alberto Ballestrero
BACKGROUND: Immunohistochemistry (IHC) and fluorescent-in situ hybridization (FISH) are standard methods to assess human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients. Real-time quantitative polymerase-chain-reaction (qRT-PCR) is able to detect HER2 overexpression. Here we compared FISH, IHC, quantitative PCR (qPCR), and qRT-PCR to determine the concordance rates and evaluate their relative roles in HER2 determination. PATIENTS AND METHODS: We determined HER2 status in 153 BC patients, using IHC, FISH, Q-PCR and qRT-PCR...
May 1, 2017: Journal of Translational Medicine
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