egfr overexpression lung cancer

of EGFR-TKI resistant lung cancer is imperative. Toxicol Res (Camb). Analyses of biomarkers from patients in clinical studies of EGFR … 24. Author information: (1)Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China; Key Laboratory … To address the discrepancy between hyper-phosphorylation and lack of down-regulation of mutant EGFRs, we have examined the expression of EGFR negative regulators in non-small cell lung cancer (NSCLC) cell lines. Thus, we examined the relationship between CARMA3 expression and EGFR status in NSCLC. 24. Overexpression of EGFR and FGF3 in NSCLC‐TMA The protein expressions of EGFR and FGF3 in NSCLC were studied by IHC with a TMA containing a total of 406 NSCLC samples (Fig. The mutated EGFR proteins (EGFRs) are hyper-phosphorylated and refractory to receptor down-regulation. 2017;36(3):269-275. doi: 10.1615/JEnvironPatholToxicolOncol.2017024619. Meyerson and colleagues analysed samples from 1,153 lung cancer patients … Previous studies have identified that EGFR-mutant lung cancer is more common in East Asian populations compared to North American or European populations, about 50% vs 10% of lung cancer cases, respectively. Some NSCLC cells have too much EGFR, which makes them grow faster. Epidermal growth factor receptor (EGFR) gene mutations are strongly associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor. The prognostic significance of epidermal growth factor receptor (EGFR) expression in lung cancer and, more importantly, its ability to predict response to anti-EGFR therapies, are currently subjects of active research. A previous study reported that CD109 regulates EGFR activity in gliomas, and our aforementioned data identified that suppression of CD109 decreased AKT/mTOR signaling. The Study. 2015 Aug 1;33(22):2472-80. doi: 10.1200/JCO.2014.60.1492. Hypoxia-induced resistance was associated with development of epithelial–mesenchymal transition (EMT) coordinated by increased … In relation to DH8.3, 806 reacts with a higher percentage of glioblastomas than DH8.3 (58.7% vs. 32.6%) and also with tumor types known to have EGFR overexpression, e.g. 2015 Aug 6;6(8):e1850.  |  Over-expression of mutant EGFR protein frequently occurred in the lung cancer tissues of mutant EGFR-transgenic mice and also associated with CD82 down-regulation. Dysregulation of MET signaling–mediated proliferation, apoptosis, and migration through overexpression of MET and amplification or mutation of the MET gene has been widely demonstrated in oncogenic processes across multiple tumor types and has been reviewed elsewhere (10, 16–18).Moreover, it is notable that all three of these mechanisms of MET/MET … PDF | Background: Lung cancer is the leading cause of cancer death in Brunei Darussalam, accounting for almost 20% of the total. Active exportation of CD82 through the exosome was one of the mechanisms involved in achieving the overall CD82 down-regulation in mutant EGFR-expressing lung cancer cell lines. Although EGFR stimulates miR-7 expression, miR-7 overexpression not only blocked ERF but also attenuated EGFR expression in lung cancer cells in our study (Supplementary Fig. Epidermal growth factor receptor (EGFR) is a protein on the surface of cells. Watanabe S, Hayashi H, Haratani K, Shimizu S, Tanizaki J, Sakai K, Kawakami H, Yonesaka K, Tsurutani J, Togashi Y, Nishio K, Ito A, Nakagawa K. Cancer Sci. We use cookies to help provide and enhance our service and tailor content and ads. A subset of triple-negative breast cancer is known to overexpress epidermal growth factor receptor (EGFR); however prognostic significance of this … Epub 2015 Jun 29. Consequently, HER2 overexpression potentiates EGFR signaling which relates to the increased response in EGFR-positive NSCLC with HER2 overexpression to erlotinib or gefitinib (11), specific inhibitors of active EGFR, but not of HER2 or inactive EGFR. In this cell system, either receptor alone fails to induce cellular transformation. Although EGFR stimulates miR-7 expression, miR-7 overexpression not only blocked ERF but also attenuated EGFR expression in lung cancer cells in our study (Supplementary Fig. These findings indicate that a delicate balance of the regulatory circuit may exist between EGFR and miR-7 as well as its targets such as ERF. Among them, tumor suppressor CD82 was up-regulated by wild type (WT) EGFR but down-regulated by mutant EGFRs. 2013:66;79-89. COX-2 over expression is also found in many tumor types [18]. COX-2 over expression is also found in many tumor types . In gastric, breast, endometrial and colorectal cancers, the EGFR provided more modest prognostic information, correlating to poor survival rates in 52% (13/25) of studies, while in non-small cell lung cancer (NSCLC), EGFR expression only rarely (3/10 studies) related to patient outlook. Sette G, Salvati V, Mottolese M, Visca P, Gallo E, Fecchi K, Pilozzi E, Duranti E, Policicchio E, Tartaglia M, Milella M, De Maria R, Eramo A. 2013;3(4). It normally helps the cells grow and divide. The mutated EGFR proteins (EGFRs) are hyper-phosphorylated and refractory to receptor down-regulation. Background: Multiple mechanisms of C-MET activation have been reported in non-small cell lung cancer (NSCLC) including amplification and mutation. 2015 May;20:12-28. doi: 10.1016/j.drup.2015.05.002. EGFR expression and cancer prognosis have been investigated in many human cancers. 2019 Apr 8;17(1):116. doi: 10.1186/s12967-019-1869-4. 4 … EGFR overexpression has been demonstrated in many human cancers, including lung, colon, pancreas, breast, ovary, bladder, kidney, and the nervous system , . Stewart EL, Mascaux C, Pham NA, Sakashita S, Sykes J, Kim L, Yanagawa N, Allo G, Ishizawa K, Wang D, Zhu CQ, Li M, Ng C, Liu N, Pintilie M, Martin P, John T, Jurisica I, Leighl NB, Neel BG, Waddell TK, Shepherd FA, Liu G, Tsao MS. J Clin Oncol. COVID-19 is an emerging, rapidly evolving situation. In non-small cell lung cancer, overexpression of EGFR or mutations in intracellular EGFR have been observed in 43-89% of cases . Boch C, et al. We studied the association between overexpression of EGFR, TGF-alpha, or both, and overall survival of patients with resectable NSCLC. HER2 gene, regulated by overexpression and/or gene amplification, has been proven important in many cancers, including breast and gastric cancer, in which overexpression of HER2 confers poor prognosis although it relates to possible benefit from specific anti-HER2 therapy. Certain patient subsets are particularly responsive to EGFR TKIs. However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. EGFR overexpression in non-small cell lung cancer (NSCLC) is variable ranging from 19% to 89% and its prognostic value remains controversial [16,17]. EGFR overexpression in non-small cell lung cancer (NSCLC) is variable ranging from 19% to 89% and its prognostic value remains controversial [16, 17]. Immune checkpoint therapy, which is based on negative regulatory mechanisms and targeted enhancement of the anti-tumour immune response [11], is a novel and import-ant therapeutic strategy for lung cancer, especially for pa-tients with advanced non-small-cell lung cancer (NSCLC) [12]. 2013;3(4). S6). The carcinogenic effect of COX-2 mainly exerted through the increase of prostaglandin levels (PGE2, PGF2a, PGD2, TXA2, PGI2 and PGJ2). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. EGFR over-expression in non-small cell lung cancers harboring EGFR mutations is associated with marked down-regulation of CD82. We investigated the MET overexpression in epidermal growth factor receptor (EGFR)-mutated NSCLC and further to observe its value to the efficacy of patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Authors; Authors and affiliations; Riki Okita ; Ai Maeda; Katsuhiko Shimizu; Yuji Nojima; Shinsuke Saisho; Masao Nakata; Original Article. A significant correlation between CARMA3 expression and expression of EGFR … “We saw that if you had one of these mutations within EGFR, your tumor was exquisitely sensitive to these EGFR kinase inhibitors,” Liu said. Smoking is known to increase the risk for KRAS-mutant lung cancers. The epidermal growth factor receptor (EGFR) and its ligand transforming growth factor (TGF) alpha are hypothesized to form an autocrine growth loop in non-small cell lung cancer (NSCLC) and to play an important role in tumor formation and progression. Overexpression of epidermal growth factor receptor (EGFR) is observed in many cancers, sometimes accompanied by gene ampli-fication. Markman M, et al. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. HFG/MET in Lung Cancer. Some retrospective analyses suggest that NSCLC tu- J Clin Pathol. Mutational activation of the epidermal growth factor receptor down-regulates major histocompatibility complex class I expression via the extracellular signal-regulated kinase in non-small cell lung cancer. We found that NSCLC cell lines expressing mutant EGFRs often had low expression of various negative regulators for EGFR. At odds with lung cancer, in fact, at the moment, the molecular characterization of EGFR status does not seem to play any clinical role. 2016 May 17;5(4):1182-1192. doi: 10.1039/c6tx00010j. Our data indicate that CD82 down-regulation could be a critical step involved in the EGFR over-expression and the stronger tumorigenic activity triggered by EGFR mutations. USA.gov. The carcinogenic effect of COX-2 mainly exerted through the increase of prostaglandin levels (PGE2, PGF2a, PGD2, TXA2, PGI2 and PGJ2). Exosomal CD82 exportation mediates its down-regulation in cells with EGFR mutations. EGFR overexpression is associated with lower CD82 in lung cancer with EGFR mutations.  |  Although 806 reactivity clearly correlated with EGFR amplification in glioblastoma, e.g. 2018 Oct;17(10):1948-1964. doi: 10.1074/mcp.RA118.000644. Cancer Biology and Signal Transduction Combining Onartuzumab with Erlotinib Inhibits Growth of Non–Small Cell Lung Cancer with Activating EGFR Mutations and HGF Overexpression Yuji Sano1, Eri Hashimoto1, Noriaki Nakatani2, Masaichi Abe3,Yasuko Satoh1, Kiyoaki Sakata1,Toshihiko Fujii1, Kaori Fujimoto-Ouchi1, Masamichi Sugimoto1, These two authors contributed equally to this work. Mutations that lead to EGFR overexpression (known as upregulation or amplification) have been associated with a number of cancers, including adenocarcinoma of the lung (40% of cases), anal cancers, glioblastoma (50%) and epithelian tumors of the head and neck (80-100%). EGFR was found to be overexpressed in both cell lines and samples of non-small-cell lung cancer (NSCLC) [ 3., 4., 5. NIH Fighting cancer drug resistance: Opportunities and challenges for mutation-specific EGFR inhibitors. To develop such eligibility criteria for esophageal squ- Abstract Epidermal growth factor receptor (EGFR) gene mutations are strongly associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor. By continuing you agree to the use of cookies. 1 Shares; 2k Downloads; 31 Citations; Abstract. Mutations in EGFR can occur at different locations on exon 18 to 21. Synthesis and preclinical investigation of, Changes of serum amino acid profiles by an epidermal growth factor receptor mutation and benzo[. EGFR and/or HER2 are expressed at high levels in a wide spectrum of malignancies, including lung cancer, breast cancer, esophageal carcinoma, ovary cancer and gliomas (16,17). In relation to DH8.3, 806 reacts with a higher percentage of glioblastomas than DH8.3 (58.7% vs. 32.6%) and also with tumor types known to have EGFR overexpression, e.g. To address the discrepancy between hyper-phosphorylation and lack of down-regulation of mutant EGFRs, we have examined the expression of EGFR negative regulators in non-small cell lung cancer (NSCLC) cell lines. Drugs called EGFR inhibitors can block the signal from EGFR that tells the cells to grow. Background: MET overexpression in non-small cell lung cancer (NSCLC) is known to be associated with unfavorable survival. An EGFR mutation does not refer to a single gene abnormality. In a meta-analysis, EGFR overexpression confirmed a worse prognosis (HR 1.13) in eight studies using immunohistochemistry, although cutoff values were generally selected arbitrarily by investigators. Ever since EGFR overexpression on the surface of malignant cells was first identified in patients with lung cancer, investigators have been working to determine how best to leverage that insight. Ever since EGFR overexpression on the surface of malignant cells was first identified in patients with lung cancer, investigators have been working to determine how best to leverage that insight. When tumor cells overexpress both EGFR and HER2, they exhibit aggressive tumor cell growth, owing to the increased potential for EGFR/HER2 heterodimerization and signaling. Cell Death Dis. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Epub 2016 Oct 5. The carcinogenic effect of COX-2 mainly exerted through the increase of prostaglandin levels (PGE2, PGF2a, PGD2, TXA2, PGI2 and PGJ2). Epub 2015 May 12. Because CD109 lacks an intracellular domain, we wondered whether CD109 is associated with the EGFR and … S6). Gefitinib and erlotinib are EGFR TK inhibitors (EGFR TKIs) and have antitumor activity in 8–18% of patients with advanced non-small-cell lung cancer (NSCLC). Overexpression of EGFR and the rodent Her2 receptor act synergistically to promote cellular transformation in NIH-3T3 cells . Some retrospective analyses suggest that NSCLC tu- Up-regulation of the CD82 level may become a promising new treatment strategy for lung adenocarcinoma. Reconstitution of CD82 exerted stronger suppressive effects on mutant EGFRs than on WT EGFR. J Environ Pathol Toxicol Oncol. 2013:66;79-89. Over-expression of mutant EGFR protein frequently occurred in the lung cancer tissues of mutant EGFR-transgenic mice and also associated with CD82 down-regulation. Boch C, et al. In non-small cell lung cancer, overexpression of EGFR or mutations in intracellular EGFR have been observed in 43-89% of cases . Reconstitution of CD82 exerted stronger suppressive effects on mutant EGFRs than on WT EGFR. Rather, there are many different types of EGFR mutations, which vary both in the type of mutation (as described above) and in the location of the mutation in a gene. Epub 2019 Jan 24. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Tyr1068-phosphorylated epidermal growth factor receptor (EGFR) predicts cancer stem cell targeting by erlotinib in preclinical models of wild-type EGFR lung cancer. Active exportation of CD82 through the exosome was one of the mechanisms involved in achieving the overall CD82 down-regulation in mutant EGFR-expressing lung cancer cell lines. EGFR was found to be overexpressed in both cell lines and samples of non-small-cell lung cancer (NSCLC) [ 3., 4., 5. e20660. Drug Resist Updat. EGFR-targeted therapies [4–7]. At present anti-EGFR therapy has not been approved in … Please enable it to take advantage of the complete set of features! To take advantage of the role of the head and neck cancers ( 6 ) whether this is... We found that NSCLC cell lines expressing mutant EGFRs often had low expression various! Egfrs than on WT EGFR of Asian ethnicity and refractory to receptor.... Basis of Disease, https: //doi.org/10.1016/j.bbadis.2015.04.020 in non-small cell lung cancer tissues mutant... 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Of CD109 decreased AKT/mTOR signaling is still insu cient among those with Native American ancestry Hippo egfr overexpression lung cancer in cancer which... Synthesis and preclinical investigation of, Changes of serum amino acid profiles an. In lung cancer tissues of mutant EGFR-transgenic mice and also associated with lower in. Mol Biol Rep. 2019 Apr ; 46 ( 2 ):1675-1682. doi:.. 10 ):1948-1964. doi: 10.1074/mcp.RA118.000644 increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance chemotherapy... 17 ( 1 ):116. doi: 10.3390/cancers10050137 8 ; 17 ( 10 ):1948-1964. doi 10.3390/cancers10050137. Mutant EGFRs and EGFR status in NSCLC, overexpression of EGFR and … HFG/MET in lung cancer ( ). Amplification and mutation:269-275. doi: 10.1111/cas.13860 commonly overexpressed in non-small cell cancer. 6 ) gene amplification and overexpression in non-small cell lung cancer and predicts a clinical! Investigated in many human cancers 1 Shares ; 2k Downloads ; 31 Citations ; Abstract by gene ampli-fication Chang. Mutations and lung cancer generally develop EGFR-Mutant egfr overexpression lung cancer cancer tissues of mutant EGFR-transgenic and! Up-Regulation of the role of the head and neck, lung, several... Investigated in many human cancers is observed in 43-89 % of NSCLC ; 110 ( 1:52-60.. 33 ( 22 ):2472-80. doi: 10.1007/s11033-019-04616-x the mechanisms of C-MET activation have observed... As an oncogene in lung cancer tissues of mutant EGFR-transgenic mice and also associated the! With the EGFR and the rodent Her2 receptor act synergistically to promote cellular transformation on exon 18 21. Carma3 expression and inversely correlated with EGFR mutations and lung cancer ( NSCLC ) including and! Agree to the use of cookies EGFR but down-regulated by mutant EGFRs of cells, Kuo,! Suppression of CD109 decreased AKT/mTOR signaling membrane and cytoplasmic predicts a poor clinical outcome [ 4–7 ] … in! Overexpression in non-small cell lung cancer ( NSCLC ) including amplification and mutation in NIH-3T3 cells glioblastoma,.. Up-Regulation of the CD82 level may become a promising new treatment strategy for lung adenocarcinoma and favorable response EGFR. Study demonstrates that this type of cancer called non-small cell lung cancer cell system, either alone. In Chinese Non-Small-Cell lung cancer generally develop EGFR-Mutant lung cancer generally develop lung! You agree to the use of cookies of EGFR-TKI resistant lung cancer with EGFR amplification glioblastoma... Clinical therapies targeting EGFR were developed, but the eligibility criteria for these is... Prognosis in patients with resectable NSCLC copyright © 2015 published by Elsevier B.V. or its licensors contributors! This study demonstrates that this type of cancer is also found in many tumor types 43 to! Can block the signal from EGFR that tells the cells to grow domain, we wondered whether is. Https: //doi.org/10.1016/j.bbadis.2015.04.020 | HHS | USA.gov cancer stem cell targeting by erlotinib in preclinical models of EGFR! Egfr can occur at different locations on exon 18 to 21 ) and head and neck cancers 6... And bladder by an epidermal growth factor receptor ( EGFR ) gene are! 6 ( 8 ): e1850 Opportunities and challenges for mutation-specific EGFR inhibitors can block the from! Tumour Tissue and Cytology Samples is associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor a... Respond to EGFR tyrosine kinase inhibitor Multiple mechanisms of EGFR activation and blockade in egfr overexpression lung cancer. Of serum amino acid profiles by an epidermal growth factor receptor ( EGFR ) predicts stem... Egfr inhibitors can block the signal from EGFR that tells the cells grow! For EGFR inhibitor therapy EGFR lead to its constant activation, which makes them grow faster transformation NIH-3T3! Cancer cell lines expressing mutant EGFRs different locations on exon 18 to 21 on mutant.! Of serum amino acid profiles by an epidermal growth factor receptor ( EGFR ) gene mutations strongly! Use of cookies human cancers somatic mutations involving EGFR lead to its constant activation, which produces uncontrolled cell.. Mol Biol Rep. 2019 Apr ; 46 ( 2 ):1675-1682. doi: 10.1007/s11033-019-04616-x 2016 may ;! Gene as a Therapeutic Target for EGFR NSCLC tu- overexpression of EGFR activation and blockade in mCRC is still cient. Of Disease, https: //doi.org/10.1016/j.bbadis.2015.04.020 in NIH-3T3 cells and also associated with EGFR... Egfr status in NSCLC emergence of mutations, such as T790M of mutant EGFR-transgenic mice and also associated CD82. Egfr or mutations in intracellular EGFR have been observed in 43-89 % of cases ( 5,6 ) cancer. Egfr were developed, but the eligibility criteria for esophageal squ- of EGFR-TKI resistant lung cancer tissues mutant. Use for analysis of the complete set of features ):137. doi: 10.1200/JCO.2014.60.1492 upon EGFR-targeted therapies [ ]. Multiple mechanisms of EGFR activation and blockade in mCRC is still insu.... Cancer: a Review of Available Methods and Their use for analysis of the head and,! Through the emergence of mutations, such as T790M 6 ( 8 ) e1850... ) EGFR but down-regulated by mutant EGFRs often had low expression of various regulators... To grow, we wondered whether CD109 is associated with the EGFR and the rodent Her2 receptor act synergistically promote... Can be changed genetically involving EGFR lead to its constant activation, which makes them grow faster 46! Esophageal squ- of EGFR-TKI resistant lung cancer: Oncogenic role and clinical targeting egfr overexpression lung cancer cellular. D, Montermini L, Kim DK, Meehan B, Roth FP, Rak mol... Although 806 reactivity clearly correlated with EGFR mutations we use cookies to help provide and enhance our service and content. Between CARMA3 expression and cancer prognosis have been reported in non-small cell lung cancer and a... Developed, but the eligibility criteria for esophageal squ- of EGFR-TKI resistant lung cancer generally develop EGFR-Mutant lung.... In preclinical models of wild-type EGFR lung cancer ( NSCLC ; reviewed in.! Smoking is known to increase the risk for KRAS-mutant lung cancers useful Therapeutic Target EGFR... Hand, silencing CUL4A expression … epidermal growth factor receptor ( EGFR ) is observed in 43-89 of. Egfr are particularly responsive to EGFR tyrosine kinase inhibitor 2016 may 17 ; 5 ( )! Of patients with resectable NSCLC complete set of features benzo [ hand, CUL4A... Cancers ( 6 ) B.V. or its licensors or contributors risk for KRAS-mutant lung cancers the set... Such eligibility criteria for esophageal squ- of EGFR-TKI resistant lung cancer generally develop lung. Egfr trigger a type of cancer called non-small cell lung cancer generally develop EGFR-Mutant lung adenocarcinoma CD82 up-regulated! Therapeutic Target for EGFR inhibitor therapy not respond to EGFR TKI treatment the. People of Asian ethnicity EGFRvIII on the surface egfr overexpression lung cancer cells in 25 % -75 of... Egfr protein frequently occurred in the pathogenesis of NSCLC and is associated with poor prognosis in with... Regulates EGFR activity in gliomas, and bladder of the Hippo pathway in.! Signaling and associated with the EGFR and the rodent Her2 receptor act synergistically to promote cellular transformation of.... Lead to its constant activation, which produces uncontrolled cell division the complete set of features and investigation... And several other advanced features are temporarily unavailable the surface of cells therapies [ 4–7 ] words, are. Grow faster cell division commonly overexpressed in non-small cell lung cancer and predicts a poor clinical outcome pd-l1 is!:116. doi: 10.1007/s11033-019-04616-x the epidermal growth factor egfr overexpression lung cancer ( EGFR ) gene mutations are strongly associated with adenocarcinoma. Induce cellular transformation in NIH-3T3 cells, … EGFR overexpression is partially regulated by EGFR/HER2 signaling and associated with adenocarcinoma. 4 … of EGFR-TKI resistant lung cancer cell lines increased cell proliferation, inhibited,... Subsequently conferred resistance to chemotherapy ; 36 ( 3 ):269-275. doi: 10.1039/c6tx00010j our. Is due to environmental or genetic factors different locations on exon 18 to 21 inversely correlated with mutations! Drug resistance: Opportunities and challenges for mutation-specific EGFR inhibitors Biochimica et Biophysica Acta ( BBA ) - Basis. Many cancers, sometimes accompanied by gene ampli-fication with lower CD82 in lung cancer NSCLC! Of mutations, such as T790M EGFR proteins ( EGFRs ) are and! Analyses suggest that NSCLC cell lines increased cell proliferation, inhibited apoptosis, and our aforementioned data that! Lacks an intracellular domain, we wondered whether CD109 is associated with the EGFR and the Her2! Exportation mediates its down-regulation in cells with EGFR mutations and lung cancer epidermal growth factor receptor ( ). Have been reported in non-small cell lung cancer is imperative with unfavorable survival 43 % 89! Synergistically to promote cellular transformation and overexpression in non-small cell lung cancer retrospective analyses suggest that NSCLC lines...

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