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https://www.readbyqxmd.com/read/29440899/aptamer-drug-conjugate-targeted-delivery-of-doxorubicin-in-a-her3-aptamer-functionalized-liposomal-delivery-system-reduces-cardiotoxicity
#1
Xiao-Qian Dou, Hua Wang, Jing Zhang, Fang Wang, Gui-Li Xu, Cheng-Cheng Xu, Huan-Hua Xu, Shen-Si Xiang, Jie Fu, Hai-Feng Song
Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs. Methods: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29440293/a-correlative-analysis-of-pd-l1-pd-1-pd-l2-egfr-her2-and-her3-expression-in-oropharyngeal-squamous-cell-carcinoma
#2
Conor E Steuer, Christopher C Griffith, Sreenivas Nannapaneni, Mihir R Patel, Yuan Liu, Kelly R Magliocca, Mark W El-Deiry, Cynthia Cohen, Taofeek K Owonikoko, Dong M Shin, Zhuo Georgia Chen, Nabil F Saba
We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by immunohistochemistry on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0-4 within the tumor mass and peritumoral stroma...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29440171/crosstalk-signaling-between-her3-and-hpv16-e6-and-e7-mediates-resistance-to-pi3k-inhibitors-in-head-and-neck-cancer
#3
Toni M Brand, Stefan Hartmann, Neil E Bhola, Hua Li, Yan Zang, Rachel A O'Keefe, Max V Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Nevan J Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Theresa LaVallee, Daniel E Johnson, Michelle A Ozbun, Julie E Bauman, Jennifer R Grandis
Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the phosphatidylinositol 3-kinase (PI3K) pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29437790/her3-mediated-resistance-to-hsp90-inhibition-detected-in-breast-cancer-xenografts-by-affibody-based-pet-imaging
#4
Carlos Daniel Martins, Chiara Da Pieve, Thomas A Burley, Rhodri Smith, Daniela M Ciobota, Louis Allott, Kevin Harrington, Wim J G Oyen, Graham Smith, Gabriela Kramer-Marek
PURPOSE: Recent studies have highlighted a role of human epidermal growth factor receptor 3 (HER3) in HER2-driven cancers (e.g. breast cancer) implicating the up-regulation of the receptor in resistance to HER-targeted therapies and Hsp90 inhibitors (e.g. AUY922). Therefore, we have developed an affibody-based PET radioconjugate that quantitatively assesses HER3 changes induced by Hsp90 inhibition in vivo Experimental Design: Z HER3:8698 affibody molecules were conjugated via the C-terminus cysteine to DFO-maleimide for 89 Zr radiolabeling...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436155/design-of-cyclic-and-d-amino-acids-containing-peptidomimetics-for-inhibition-of-protein-protein-interactions-of-her2-her3
#5
Sandeep Pallerla, Himgauri Naik, Sitanshu Singh, Ted Gauthier, Rushikesh Sable, Seetharama D Jois
HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2-positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2-mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18) exhibited antiproliferative activity in HER2-overexpressing lung cancer cell lines with IC50 values in the nanomolar concentration range...
February 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29434878/progesterone-impairs-herceptin-effect-on-breast-cancer-cells
#6
Kamila Kitowska, Agnieszka Kowalska, Magdalena Mieszkowska, Dominika Piasecka, Andrzej C Skladanowski, Hanna M Romanska, Rafal Sadej
Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases. Approximately one-third of patients relapse despite treatment. Therefore numerous studies have investigated the molecular mechanisms associated with Herceptin resistance...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434875/soluble-her3-predicts-survival-in-bladder-cancer-patients
#7
Ashfaque A Memon, Stephen C Gilliver, Michael Borre, Jan Sundquist, Kristina Sundquist, Ebba Nexo, Boe S Sorensen
The role of soluble human epidermal growth factor receptor (sHER3) in bladder cancer remains unclear. In the present study, an ELISA was developed for the quantification of sHER3 and its role was investigated in patients with bladder cancer (n=82) followed for 10 years. Furthermore, the effects of sHER3 on bladder cancer cell growth and migration were also investigated. The results demonstrated that plasma sHER3 levels were significantly higher in non-invasive tumours (Ta) compared with muscle-invasive tumours (T2-T4)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29430509/molecular-correlates-of-in-vitro-responses-to-dacomitinib-and-afatinib-in-bladder-cancer
#8
Shuzo Tamura, Yin Wang, Brendan Veeneman, Daniel Hovelson, Armand Bankhead, Luke J Broses, Guadalupe Lorenzatti Hiles, Monica Liebert, John R Rubin, Kathleen C Day, Maha Hussain, Nouri Neamati, Scott Tomlins, Philip L Palmbos, Petros Grivas, Mark L Day
Background: The HER family of proteins (EGFR, HER2, HER3 and HER4) have long been thought to be therapeutic targets for bladder cancer, but previous clinical trials targeting these proteins have been disappointing. Second generation agents may be more effective. Objective: The aim of this study was to evaluate responses to two second-generation irreversible tyrosine kinase inhibitors, dacomitinib and afatinib, in bladder cancer cell lines. Methods: Cell lines were characterized by targeted next generation DNA sequencing, RNA sequencing, western blotting and flow cytometry...
January 20, 2018: Bladder Cancer
https://www.readbyqxmd.com/read/29422137/treating-resistant-tumors-using-her3-targeted-nanobiologics
#9
EDITORIAL
Kinam Park
No abstract text is available yet for this article.
February 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29420467/her-kinase-inhibition-in-patients-with-her2-and-her3-mutant-cancers
#10
David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger, Ingrid A Mayer, Valentina Boni, Emiliano Calvo, Sherene Loi, Albert C Lockhart, Joseph P Erinjeri, Maurizio Scaltriti, Gary A Ulaner, Juber Patel, Jiabin Tang, Hannah Beer, S Duygu Selcuklu, Aphrothiti J Hanrahan, Nancy Bouvier, Myra Melcer, Rajmohan Murali, Alison M Schram, Lillian M Smyth, Komal Jhaveri, Bob T Li, Alexander Drilon, James J Harding, Gopa Iyer, Barry S Taylor, Michael F Berger, Richard E Cutler, Feng Xu, Anna Butturini, Lisa D Eli, Grace Mann, Cynthia Farrell, Alshad S Lalani, Richard P Bryce, Carlos L Arteaga, Funda Meric-Bernstam, José Baselga, David B Solit
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials...
February 8, 2018: Nature
https://www.readbyqxmd.com/read/29414302/imaging-of-human-epidermal-growth-factor-receptors-for-patient-selection-and-response-monitoring-from-pet-imaging-and-beyond
#11
Patricia M R Pereira, Lolkje Abma, Kelly E Henry, Jason S Lewis
The Human Epidermal Growth Factor Receptor (ErbB/HER) family - EGFR/HER1, ErbB-2/HER2, ErbB-3/HER3, and ErbB-4/HER4 - play a key role in tumor development. Moreover, positive status of HER2 and specific mutations of EGFR are necessary to initiate HER2 directed and EGFR mutation directed therapies. The status of these receptors is usually determined by assaying biopsy specimens of tumor tissues; however, tissue samples are insufficient to account for the complex dynamics and heterogeneity involved in HER status...
January 27, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29413684/human-epidermal-receptor-family-inhibitors-in-patients-with-erbb3-mutated-cancers-entering-the-back-door
#12
Loic Verlingue, Antoine Hollebecque, Ludovic Lacroix, Sophie Postel-Vinay, Andrea Varga, Yolla El Dakdouki, Capucine Baldini, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Olivier Mir, Monica Arnedos, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Fabrice André, Eric Deutsch, Jean-Yves Scoazec, Jean-Charles Soria, Christophe Massard
INTRODUCTION: Therapeutic inhibition of the human epidermal receptor 3 (ERBB3, HER3) has been challenged by the low frequency of ERBB3 somatic alterations across cancer types. We have evaluated the clinical utility to use available inhibitors of the HER family in the context of ERBB3 mutations. PATIENTS AND METHODS: In this study, we have selected patients with somatic ERBB3 alterations detected in their tumours from the molecular screening programs running at our institution...
January 27, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29413056/egfr-mediated-interleukin-enhancer-binding-factor-3-contributes-to-formation-and-survival-of-cancer-stem-like-tumorspheres-as-a-therapeutic-target-against-egfr-positive-non-small-cell-lung-cancer
#13
Chun-Chia Cheng, Kuei-Fang Chou, Cheng-Wen Wu, Nai-Wen Su, Cheng-Liang Peng, Ying-Wen Su, Jungshan Chang, Ai-Sheng Ho, Huan-Chau Lin, Caleb Gon-Shen Chen, Bi-Ling Yang, Yu-Cheng Chang, Ya-Wen Chiang, Ken-Hong Lim, Yi-Fang Chang
OBJECTIVES: YM155, an inhibitor of interleukin enhancer-binding factor 3 (ILF3), significantly suppresses cancer stemness property, implying that ILF3 contributes to cell survival of cancer stem cells. However, the molecular function of ILF3 inhibiting cancer stemness remains unclear. This study aimed to uncover the potential function of ILF3 involving in cell survival of epidermal growth factor receptor (EGFR)-positive lung stem-like cancer, and to investigate the potential role to improve the efficacy of anti-EGFR therapeutics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29409974/survivin-targeting-mir-542-3p-overcomes-her3-signaling-induced-chemoresistance-and-enhances-the-antitumor-activity-of-paclitaxel-against-her2-overexpressing-breast-cancer
#14
Hui Lyu, Shuiliang Wang, Jingcao Huang, Bolun Wang, Zhimin He, Bolin Liu
Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation...
January 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29371993/genomic-alterations-of-erbb-receptors-in-cancer-clinical-implications
#15
REVIEW
Rosalin Mishra, Ariella B Hanker, Joan T Garrett
The ERBB family of receptor tyrosine kinases has been implicated in carcinogenesis for over three decades with rigorous attention to EGFR and HER2. ERBB receptors, consisting of EGFR, HER2, HER3, and HER4 are part of a complicated signaling network that activates downstream signaling pathways including PI3K/AKT, Ras/Raf/MAPK, JAK/STAT and PKC. It is well established that EGFR is amplified and/or mutated in gliomas and non-small-cell lung carcinoma while HER2 is amplified and/or over-expressed in breast, gastric, ovarian, non-small cell lung carcinoma, and several other tumor types...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29361822/ligand-independent-epidermal-growth-factor-receptor-overexpression-correlates-with-poor-prognosis-in-colorectal-cancer
#16
Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Purpose: Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients' survival with CRC. Materials and Methods: The expression of EGFR ligands, including heparin binding epidermal growth factor like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH)...
January 17, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29358026/regulation-of-kinase-activity-in-the-caenorhabditis-elegans-egf-receptor-let-23
#17
Lijun Liu, Tarjani M Thaker, Daniel M Freed, Nicole Frazier, Ketan Malhotra, Mark A Lemmon, Natalia Jura
In the active HER receptor dimers, kinases play distinct roles; one is the catalytically active kinase and the other is its allosteric activator. This specialization enables signaling by the catalytically inactive HER3, which functions exclusively as an allosteric activator upon heterodimerization with other HER receptors. It is unclear whether the allosteric activation mechanism evolved before HER receptors functionally specialized. We determined the crystal structure of the kinase domain of the only EGF receptor in Caenorhabditis elegans, LET-23...
January 17, 2018: Structure
https://www.readbyqxmd.com/read/29349598/phase-ib-study-evaluating-safety-and-clinical-activity-of-the-anti-her3-antibody-lumretuzumab-combined-with-the-anti-her2-antibody-pertuzumab-and-paclitaxel-in-her3-positive-her2-low-metastatic-breast-cancer
#18
Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts)...
January 19, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#19
Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, James Sun, Vincent A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29326440/braf-inhibition-upregulates-a-variety-of-receptor-tyrosine-kinases-and-their-downstream-effector-gab2-in-colorectal-cancer-cell-lines
#20
Ricarda Herr, Sebastian Halbach, Miriam Heizmann, Hauke Busch, Melanie Boerries, Tilman Brummer
BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single agents. This unresponsiveness was mechanistically attributed to the loss of negative feedbacks on the epidermal growth factor receptor (EGFR) and initiated clinical trials that combine BRAF (and MEK) inhibitors, either singly or in combination, with the anti-EGFR antibodies cetuximab or panitumumab...
January 12, 2018: Oncogene
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