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• W3082476077 abstract "// Dimitra P. Vageli 1 , David Kasle 1 , Sotirios G. Doukas 1 , Panagiotis G. Doukas 1 and Clarence T. Sasaki 1 1 The Yale Larynx Laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA Correspondence to: Clarence T. Sasaki, email: clarence.sasaki@yale.edu Keywords: NF-&#x03BA;B inhibition; BAY 11-7082; bile; laryngopharyngeal reflux; hypopharyngeal cancer Received: May 07, 2020     Accepted: July 27, 2020     Published: September 01, 2020 ABSTRACT Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-&#x03BA;B-related pathway. We hypothesize that topical pre- or post-application of pharmacologic NF-&#x03BA;B inhibitor, BAY 11-7082 (0.25 &#x03BC;mol), on murine (C57BL/6J) HM (twice a day for 10 days) can effectively inhibit acidic bile (10 mmol/l; pH 3.0) induced oncogenic molecular events, similar to prior in vitro findings. We demonstrate that the administration of BAY 11-7082, either before or after acidic bile, eliminates NF-&#x03BA;B activation, prevents overexpression of Bcl2, Rela, Stat3, Egfr, Tnf, Wnt5a, and deregulations of miR-192 , miR-504 , linked to bile reflux-related hypopharyngeal cancer. Pre- but not post-application of NF-&#x03BA;B inhibitor, significantly blocks overexpression of Il6 and prostaglandin H synthases 2 ( Ptgs2 ), and reverses miR-21, miR-155, miR-99a phenotypes, supporting its early bile-induced pro-inflammatory effect. We thus provide novel evidence that topical administration of a pharmacological NF-&#x03BA;B inhibitor, either before or after acidic bile exposure can successfully prevent its oncogenic mRNA and miRNA phenotypes in HM, supporting the observation that co-administration of NF-&#x03BA;B inhibitor may not be essential in preventing early bile-related oncogenic events and encouraging a capacity for further translational exploration." @default.
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• W3082476077 date "2020-09-01" @default.
• W3082476077 modified "2023-09-25" @default.
• W3082476077 title "The temporal effects of topical NF-<i>κB</i> inhibition, in the <i>in vivo</i> prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model" @default.
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• W3082476077 doi "https://doi.org/10.18632/oncotarget.27706" @default.
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