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https://www.readbyqxmd.com/read/29039474/evaluation-of-a-radiocobalt-labelled-affibody-molecule-for-imaging-of-human-epidermal-growth-factor-receptor-3-expression
#1
Maria Rosestedt, Ken G Andersson, Bogdan Mitran, Sara S Rinne, Vladimir Tolmachev, John Löfblom, Anna Orlova, Stefan Ståhl
The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated...
October 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29024937/protein-biomarkers-predictive-for-response-to-anti-egfr-treatment-in-ras-wild-type-metastatic-colorectal-carcinoma
#2
Astrid Lièvre, Bérèngere Ouine, Jim Canet, Aurélie Cartier, Yael Amar, Wulfran Cacheux, Odette Mariani, Rosine Guimbaud, Janick Selves, Thierry Lecomte, Serge Guyetant, Ivan Bieche, Frédérique Berger, Leanne de Koning
BACKGROUND: Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. However, even among RAS wild-type (WT) patients, only a fraction responds to anti-EGFR therapy, suggesting that other mechanisms of resistance exist. We hypothesise that different (epi)genetic alterations can lead to primary anti-EGFR resistance and that the crucial end point is the activation of protein signalling pathways...
October 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28979811/a-novel-multi-target-inhibitor-harboring-selectivity-of-inhibiting-egfr-t790m-sparing-wild-type-egfr
#3
Xiaoping Song, Xin Qi, Qiang Wang, Weiming Zhu, Jing Li
Non-Small Cell Lung Cancer (NSCLC) is driven by a variety of deregulated kinases and the development of multi-target inhibitor for multiple signaling pathways or multiple steps is required. Here, we reported that ZWM026, an indolocarbazoles analogue, derived from mangrove in coastal marine wetland, exhibited selectivity and reversibility against T790M mutant over wild-type EGFR in naturally occurring NSCLC cells and constructed NIH-3T3 cells. It simultaneously inhibited activities of HER2, HER3, HER4 and RET but was different from current multi-target kinase inhibitors...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978022/prognostic-significance-of-her3-in-patients-with-malignant-solid-tumors
#4
Qin Li, RuiXue Zhang, Han Yan, PengFei Zhao, Li Wu, Hui Wang, Teng Li, Bangwei Cao
Human epidermal growth factor receptor 3 (HER3) is closely involved in tumor progression and is an important target of therapy. To evaluate the prognostic significance of HER3 in malignant solid tumors, we searched the PUBMED, EMBASE and CNKI databases for relevant studies written in English or Chinese up to December 2015. Fifteen studies comprising 2964 patients were identified. The HER3(+) rate ranged from 9.0-75.1 % in malignant solid tumors: 30.3-75.1 % in breast cancers, 51.1-74.5 % in colorectal cancers, 13...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963699/nrg-1-stimulates-serum-dj-1-increase-in-breast-cancers
#5
Yuandong Wang, Yan Zhang, Qian Lu, Yiming Wang, Xinchen Sun, Shu Zhang
To explore the relationship between the expression of DJ-1/HER3 and tumor grade in breast cancer, and investigate the effect of HER3 on NRG-1-mediated serum DJ-1 level in vivo. We analyze the expression level of DJ-1 and HER3 in 68 patients with different grades of breast cancer by immunostaining the tissue microarray. Besides, we investigated the serum DJ-1 level by ELISA. We found that the detectable DJ-1 protein expression is decreased, and the HER3 expression is increased in tumor tissue with the progression of breast cancer...
September 30, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28961833/biomarkers-predict-enhanced-clinical-outcomes-with-afatinib-versus-methotrexate-in-patients-with-second-line-recurrent-and-or-metastatic-head-and-neck-cancer
#6
E E W Cohen, L F Licitra, B Burtness, J Fayette, T Gauler, P M Clement, J J Grau, J M Del Campo, A Mailliez, R I Haddad, J B Vermorken, M Tahara, J Guigay, L Geoffrois, M C Merlano, N Dupuis, N Krämer, X J Cong, N Gibson, F Solca, E Ehrnrooth, J-P H Machiels
Background: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. Patients and methods: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week)...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28959366/mode-of-action-of-pertuzumab-in-combination-with-trastuzumab-plus-docetaxel-therapy-in-a-her2-positive-breast-cancer-xenograft-model
#7
Yoriko Yamashita-Kashima, Sei Shu, Keigo Yorozu, Yoichiro Moriya, Naoki Harada
In a Phase III trial for HER2-positive breast cancer (the CLEOPATRA study), the triple-drug combination arm of pertuzumab plus trastuzumab plus docetaxel showed significantly longer progression-free survival and overall survival than did the trastuzumab plus docetaxel arm. In this study, we investigated the mechanism of action of the triple-drug combination therapy in vivo. For this purpose, we established a mouse xenograft model using KPL-4, a HER2-positive human breast cancer cell line, in which the triple-drug combination treatment dramatically induced tumor regression compared with double-drug combinations (trastuzumab plus docetaxel, pertuzumab plus docetaxel, or pertuzumab plus trastuzumab)...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28940194/a-new-model-system-identifies-egfr-her2-and-her2-her3-heterodimers-as-potent-inducers-of-oesophageal-epithelial-cell-invasion
#8
Christiane Daniela Fichter, Camilla Maria Przypadlo, Achim Buck, Nicola Herbener, Bianca Riedel, Luisa Schäfer, Hiroshi Nakagawa, Axel Walch, Thomas Reinheckel, Martin Werner, Silke Lassmann
Oesophageal squamous cell carcinomas and oesophageal adenocarcinomas display distinct patterns of ErbB expression and dimers. The functional effects of specific ErbB homo- or heterodimers on oesophageal (cancer) cell behaviour, particularly invasion of early carcinogenesis remains unknown. Here, a new cellular model system for controlled activation of EGFR or HER2 and EGFR/HER2 or HER2/HER3 homo- and heterodimers was studied in non-neoplastic squamous oesophageal epithelial Het-1A cells. EGFR, HER2 and HER3 intracellular domains (ICDs) were fused to dimerization domains (DmrA / DmrA and DmrC), and transduced into Het-1A cells lacking ErbB expression...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28939847/dual-mab-her-family-blockade-in-head-and-neck-cancer-human-cell-lines-combined-with-photon-therapy
#9
Jean-Baptiste Guy, Benoîte Méry, Edouard Ollier, Sophie Espenel, Alexis Vallard, Anne-Sophie Wozny, Stéphanie Simonet, Alexandra Lauret, Priscillia Battiston-Montagne, Dominique Ardail, Gersende Alphonse, Chloé Rancoule, Claire Rodriguez-Lafrasse, Nicolas Magné
Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28938615/biomarker-immunoprofile-in-salivary-duct-carcinomas-clinicopathological-and-prognostic-implications-with-evaluation-of-the-revised-classification
#10
Soichiro Takase, Satoshi Kano, Yuichiro Tada, Daisuke Kawakita, Tomotaka Shimura, Hideaki Hirai, Kiyoaki Tsukahara, Akira Shimizu, Yorihisa Imanishi, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Yukiko Sato, Chihiro Fushimi, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Toyoyuki Hanazawa, Hideaki Chazono, Robert Yoshiyuki Osamura, Toshitaka Nagao
Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#11
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910149/dual-targeting-of-epidermal-growth-factor-receptor-and-her3-by-mehd7945a-as-monotherapy-or-in-combination-with-cisplatin-partially-overcomes-cetuximab-resistance-in-head-and-neck-squamous-cell-carcinoma-cell-lines
#12
Ines De Pauw, An Wouters, Jolien Van den Bossche, Vanessa Deschoolmeester, Hasan Baysal, Patrick Pauwels, Marc Peeters, Jan B Vermorken, Filip Lardon
Aberrant signaling of the epidermal growth factor receptor (EGFR) plays a crucial role in the tumorigenesis of many cancer types, including head and neck squamous cell carcinoma (HNSCC), making it a compelling drug target. After initial promising results of EGFR-targeted therapies such as cetuximab, the problem of therapeutic resistance is emerging and new treatment options are necessary. In contrast to first-generation EGFR inhibitors, MEHD7945A (duligotuzumab) is a monoclonal antibody with dual EGFR/HER3 specificity...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28899363/a-phase-i-open-label-dose-escalation-study-of-the-anti-her3-monoclonal-antibody-ljm716-in-patients-with-advanced-squamous-cell-carcinoma-of-the-esophagus-or-head-and-neck-and-her2-overexpressing-breast-or-gastric-cancer
#13
Kerry Lynn Reynolds, Philippe L Bedard, Se-Hoon Lee, Chia-Chi Lin, Josep Tabernero, Maria Alsina, Ezra Cohen, José Baselga, George Blumenschein, Donna M Graham, Ignacio Garrido-Laguna, Dejan Juric, Sunil Sharma, Ravi Salgia, Abdelkader Seroutou, Xianbin Tian, Rose Fernandez, Alex Morozov, Qing Sheng, Thiruvamoor Ramkumar, Angela Zubel, Yung-Jue Bang
BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity...
September 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28891752/development-of-emab-51-a-sensitive-and-specific-anti-epidermal-growth-factor-receptor-monoclonal-antibody-in-flow-cytometry-western-blot-and-immunohistochemistry
#14
Shunsuke Itai, Mika K Kaneko, Yuki Fujii, Shinji Yamada, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Saori Handa, Yao-Wen Chang, Hiroyoshi Suzuki, Hiroyuki Harada, Yukinari Kato
The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and is involved in cell growth and differentiation. EGFR homodimers or heterodimers with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many cancers. In this study, we developed novel anti-EGFR monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. First, we expressed the full-length or ectodomain of EGFR in LN229 glioblastoma cells and then immunized mice with LN229/EGFR or ectodomain of EGFR, and performed the first screening using enzyme-linked immunosorbent assays...
September 11, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28889394/evaluation-of-protein-levels-of-the-receptor-tyrosine-kinase-erbb3-in-serum
#15
Leandro S D'Abronzo, Chong-Xian Pan, Paramita M Ghosh
The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK) consists of four members: EGFR1/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and HER4/ErbB4. Signaling through these receptors regulates many key cellular activities, such as cell division, migration, adhesion, differentiation, and apoptosis. The ErbB family has been shown to be overexpressed in different types of cancers and is a target of several inhibitors already in clinical trials. ErbB3 lacks a functional tyrosine kinase domain and therefore has not been as extensively studied as the other members of this family, but its importance in activating downstream pathways, such as the PI3K/Akt pathway, makes this RTK a worthy investigation target, especially in urothelial carcinoma where the PI3K/Akt pathway is vital for progression...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28884521/a-single-framework-synthetic-antibody-library-containing-a-combination-of-canonical-and-variable-complementarity-determining-regions
#16
Bharathikumar Vellalore Maruthachalam, Ayman El-Sayad, Jianghai Liu, Wayne Hill, Ashley Sutherland, Landon Pastushok, Humphrey Fonge, Kris Barreto, Clarence Ronald Geyer
Synthetic antibody libraries have been used to generate antibodies with favorable biophysical and pharmacological properties. Here, we describe the design, construction, and validation of a phage-displayed Fab library built on a modified trastuzumab framework with four fixed and two diversified complementarity-determining regions (CDRs). CDRs L1, L2, H1, and H2 were fixed to preserve the most-frequent 'canonical' CDR conformation preferred by the modified trastuzumab Fab framework. The library diversity was engineered within CDRs L3 and H3 using custom-designed trinucleotide phosphoramidite mixes and biased towards human antibody CDR sequences...
September 7, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28881753/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#17
Heng-Heng Yuan, Ying-Nan Yang, Jian-Hua Zhou, Yan-Jing Li, Li-Ying Wang, Jun-Wei Qin, Tao Liu, Zhen-Zhen Li, Qing-Xin Zhou, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Wen-Jie Zhang, Lei Liu, Xiao-Xue Du, Yu Han
The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28873009/-89-zr-mab3481-pet-for-her3-tumor-status-assessment-during-lapatinib-treatment
#18
Martin Pool, Arjan Kol, Steven de Jong, Elisabeth G E de Vries, Marjolijn N Lub-de Hooge, Anton G T Terwisscha van Scheltinga
Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with tyrosine kinase inhibitor lapatinib can induce a compensatory HER3 increase, which may attenuate antitumor efficacy. Therefore, we explored in vivo HER3 tumor status assessment after lapatinib treatment with zirconium-89 ((89)Zr)-labeled anti-HER3 antibody mAb3481 positron emission tomography (PET). Lapatinib effects on HER3 cell surface expression and mAb3481 internalization were evaluated in human breast (BT474, SKBR3) and gastric (N87) cancer cell lines using flow cytometry...
September 5, 2017: MAbs
https://www.readbyqxmd.com/read/28797930/%C3%AE-tocotrienol-induced-disruption-of-lipid-rafts-in-human-breast-cancer-cells-is-associated-with-a-reduction-in-exosome-heregulin-content
#19
Osama A Alawin, Rayan A Ahmed, Venkateshwararao Dronamraju, Karen P Briski, Paul W Sylvester
Overexpression of heregulin, a potent ligand that activates HER3 and HER4 receptors, plays a significant role in the development of chemotherapy resistance in breast cancer patients. Exosomes released from cancer cells are small vesicles originating from the outward budding of lipid rafts that carry various mitogenic proteins that then act locally in an autocrine/paracrine manner to stimulate cancer cell growth. Since the anticancer activity of γ-tocotrienol has been shown to be mediated in part through the disruption of lipid rafts, studies were conducted to determine the effect of γ-tocotrienol on exosomes mitogenic biopotency...
July 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28791648/assessment-of-specificity-of-an-adenovirus-targeted-to-her3-4
#20
Sheena H MacLeod, Kyle G Potts, Shyambabu Chaurasiya, Mary M Hitt
Gene therapy with viral vectors, such as adenovirus (Ad), targeted to the human epidermal growth factor receptors 3 and 4 (HER3/4) are potentially useful for cancer therapy. Testing the expression of a reporter gene from these viruses in target cells is essential to determine functionality of the targeted virus. A competition assay with a relevant ligand (heregulin, HRG) can provide convincing evidence that blocking binding to the HER3/4 receptor results in decreased reporter gene expression. Labeling individual viruses with a fluorescent molecule allows examination of the targeted virus in specific steps in the infection...
2017: Methods in Molecular Biology
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