Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications

Recent preclinical explorations strongly support the tumorigenic potential of bile on laryngopharyngeal mucosa. Herein, the authors describe, in bile‐related human hypopharyngeal squamous cell carcinoma (HSCC), NF‐κB–related messenger RNA (mRNA) and microRNA (miRNA) oncogenic phenotypes similar to those previously identified in acidic bile–exposed premalignant murine hypopharyngeal mucosa.

• Publication year

  2019

• Venue

  Cancer

• Publication date

  2019-10-15

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/cncr.32369PMID 31310330
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma

  2019cited by this paper
• Gastroesophageal and Laryngopharyngeal Reflux Associated With Laryngeal Malignancy: A Systematic Review and Meta-analysis.

  2019cited by this paper
• Temporal characteristics of NF-κB inhibition in blocking bile-induced oncogenic molecular events in hypopharyngeal cells

  2019cited by this paper
• Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction

  2019cited by this paper
• NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

  2018cited by this paper
• Curcumin prevents the bile reflux‐induced NF‐κB‐related mRNA oncogenic phenotype, in human hypopharyngeal cells

  2018cited by this paper
• In Vivo Short-Term Topical Application of BAY 11-7082 Prevents the Acidic Bile–Induced mRNA and miRNA Oncogenic Phenotypes in Exposed Murine Hypopharyngeal Mucosa

  2018cited by this paper
• Inhibition of NF-κB prevents the acidic bile-induced oncogenic mRNA phenotype, in human hypopharyngeal cells

  2017cited by this paper
• Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

  2017cited by this paper
• Bile Acids and Esophageal Cancer

  2017cited by this paper
• miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid–Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo1

  2016cited by this paper
• Gastro-duodenal fluid induced nuclear factor-κappaB activation and early pre-malignant alterations in murine hypopharyngeal mucosa

  2016cited by this paper
• Bile acid: a potential inducer of colon cancer stem cells

  2016cited by this paper
• In vitro model for gastroduodenal reflux–induced nuclear factor‐kappaB activation and its role in hypopharyngeal carcinogenesis

  2016cited by this paper
• OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer.

  2016cited by this paper
• Inflammation and Notch signaling: a crosstalk with opposite effects on tumorigenesis

  2016cited by this paper
• Cleaved NOTCH1 Expression Pattern in Head and Neck Squamous Cell Carcinoma Is Associated with NOTCH1 Mutation, HPV Status, and High-Risk Features

  2015cited by this paper
• MiR-21/miR-375 ratio is an independent prognostic factor in patients with laryngeal squamous cell carcinoma.

  2015influential reference
• Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature

  2014cited by this paper
• Chemoprevention of head and neck squamous cell carcinoma through inhibition of NF-κB signaling.

  2014cited by this paper
• miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival.

  2014cited by this paper
• miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β.

  2013cited by this paper
• miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β He-Ping Li*,†, Xian-Cheng Zeng1,†, Bing Zhang2,†, Jian-Ting Long3, Bo Zhou, Guo-Sheng Tan, Wei-Xia Zeng4, Wei Chen and Jian-Yong Yang

  2013cited by this paper
• Gastric Reflux Is an Independent Risk Factor for Laryngopharyngeal Carcinoma

  2013cited by this paper
• Aberrant IKKα and IKKβ cooperatively activate NF-κB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer

  2013cited by this paper
• Overexpression of miR -155 Promotes Proliferation and Invasion of Human Laryngeal Squamous Cell Carcinoma via Targeting SOCS1 and STAT3

  2013cited by this paper
• [MicroRNAs regulate epithelial-mesenchymal transition of supraglottic laryngeal cancer].

  2013cited by this paper
• Inhibition of farnesoid X receptor controls esophageal cancer cell growth in vitro and in nude mouse xenografts

  2013cited by this paper
• MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer

  2013cited by this paper
• Unraveling Regulatory Programs for NF-kappaB, p53 and MicroRNAs in Head and Neck Squamous Cell Carcinoma

  2013influential reference
• Transcriptional activation of microRNA-34a by NF-kappa B in human esophageal cancer cells

  2012cited by this paper
• MicroRNA-34a affects the occurrence of laryngeal squamous cell carcinoma by targeting the antiapoptotic gene survivin

  2012cited by this paper
• NF‐κB and the link between inflammation and cancer

  2012cited by this paper
• Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine.

  2011cited by this paper
• Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells.

  2011cited by this paper
• miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC)

  2010influential reference
• Bile in the Esophagus—Model for a Bile Acid Biosensor

  2010cited by this paper
• The Molecular Pathogenesis of Head and Neck Cancer

  2010cited by this paper
• Effect of NF-κB signaling on apoptosis in chronic inflammation-associated carcinogenesis.

  2010cited by this paper
• Bile acids as endogenous etiologic agents in gastrointestinal cancer.

  2009cited by this paper
• Dysregulated molecular networks in head and neck carcinogenesis.

  2009cited by this paper
• Farnesoid X receptor antagonizes nuclear factor κB in hepatic inflammatory response

  2008cited by this paper
• Molecular biology of head and neck cancer: risks and pathways.

  2008cited by this paper
• Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe.

  2007cited by this paper
• BASIC SCIENCE REVIEW

  2007influential reference
• Gene expression profiles identify epithelial-to-mesenchymal transition and activation of nuclear factor-kappaB signaling as characteristics of a high-risk head and neck squamous cell carcinoma.

  2006cited by this paper
• Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-κB Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma

  2006cited by this paper
• Biliary laryngopharyngeal reflux: a new pathological entity

  2006cited by this paper
• Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma.

  2004influential reference
• Nuclear Factor-κB is an Important Modulator of the Altered Gene Expression Profile and Malignant Phenotype in Squamous Cell Carcinoma

  2004cited by this paper
• Determination of bile acids in biological fluids by liquid chromatography-electrospray tandem mass spectrometry.

  2001cited by this paper
• Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity

  1999cited by this paper
• Bile acids as components of the duodenogastric refluxate: detection, relationship to bilirubin, mechanism of injury, and clinical relevance.

  1999cited by this paper
• Bile acid concentrations in the refluxate of patients with reflux oesophagitis

  1988cited by this paper

• Laryngopharyngealer Reflux – Update 2025

  2025cites this paper
• The Role of Laryngopharyngeal Reflux Disease in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: A Systematic Review.

  2025cites this paper
• The Complexity of Mucosal Damage in Gastroesophageal Airway Reflux Disease: A Molecular Perspective

  2024cites this paper
• Laryngopharyngeal Reflux Pathophysiology, Clinical Presentation, and Management: A Narrative Review

  2024cites this paper
• Der laryngopharyngeale Reflux in der Praxis*

  2024cites this paper
• Novel non‐invasive molecular signatures for oral cavity cancer, by whole transcriptome and small non‐coding RNA sequencing analyses: Predicted association with PI3K/AKT/mTOR pathway

  2024cites this paper
• Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study

  2024cites this paper
• Digestive Biomarkers of Laryngopharyngeal Reflux: A Preliminary Prospective Controlled Study.

  2024cites this paper
• Diagnostic Value of Fasting and Bedtime Saliva Pepsin Measurements in Laryngopharyngeal Reflux

  2024cites this paper
• Potential Chemopreventive Role of Proton Pump Inhibitors in Head and Neck Cancer: Insights from a Nested Case–Control Analysis of a National Health Screening Cohort

  2024cites this paper
• Unveiling the mechanism of sericin and hydroxychloroquine in suppressing lung oxidative impairment and early carcinogenesis in diethylnitrosamine-induced mice by modulating PI3K/Akt/Nrf2/NF-κB signaling pathway.

  2024cites this paper
• Gastric cancer after Bariatric Bypass Surgery. Do they relate? (A Systematic Review)

  2023cites this paper
• Assessment of the risk factors of duodenogastric reflux in relation to different dietary habits in a Chinese population of the Zhangjiakou area

  2023cites this paper
• Reflux May Weaken Therapeutic Effect of Immune Checkpoint Inhibitors on Head and Neck Squamous Cell Carcinoma: A Proposed Risk Prediction Model Based on LPR/GERD-Related Genes

  2023cites this paper
• The diagnostic combination of serum circulating miR-488 and lncRNA AC018761 as biomarkers for hypopharyngeal squamous cell carcinoma (HPSCC)

  2023cites this paper
• Exosomal MicroRNA-223, MicroRNA-146, and MicroRNA-21 Profiles and Biochemical Changes in Laryngeal Cancer.

  2023cites this paper
• Saliva pepsin measurements in the detection of gastroesophageal reflux disease in laryngopharyngeal reflux patients: a cohort study

  2023cites this paper
• A Novel Saliva and Serum miRNA Panel as a potential useful index for Oral Cancer and the Association of miR-21 with smoking history: a pilot study.

  2023cites this paper
• Diagnostic Value of Pepsin Measurements in Dysphonia Attributed to Laryngopharyngeal Reflux Disease.

  2023cites this paper
• Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

  2023cites this paper
• The Real Relevance of Nonacid Reflux in Pediatric Patients

  2023cites this paper
• Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights

  2022cites this paper
• The study of laryngopharyngeal reflux needs adequate animal model

  2022cites this paper
• Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo.

  2022cites this paper
• The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells

  2022cites this paper
• The Effect of Tobacco Smoke N-Nitrosamines, NNK and NDEA, and Nicotine, on DNA Mismatch Repair Mechanism and miRNA Markers, in Hypopharyngeal Squamous Cell Carcinoma: An In Vivo Model and Clinical Evidence

  2022influential citation
• Bile reflux alters the profile of the gastric mucosa microbiota

  2022cites this paper
• Bile acids as carcinogens in the colon and at other sites in the gastrointestinal system

  2022cites this paper
• Weakly Acidic Bile Is a Risk Factor for Hypopharyngeal Carcinogenesis Evidenced by DNA Damage, Antiapoptotic Function, and Premalignant Dysplastic Lesions In Vivo

  2021cites this paper
• Does Pepsin Saliva Concentration (Peptest™) Predict the Therapeutic Response of Laryngopharyngeal Reflux Patients?

  2021cites this paper
• Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract

  2021cites this paper
• Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets

  2021cites this paper
• Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis

  2021cites this paper
• Bile reflux and hypopharyngeal cancer

  2021influential citation
• Pepsin and Laryngeal and Hypopharyngeal Carcinomas

  2020cites this paper
• The in vivo preventive and therapeutic properties of curcumin in bile reflux‐related oncogenesis of the hypopharynx

  2020cites this paper
• The Progressive Mutagenic Effects of Acidic Bile Refluxate in Hypopharyngeal Squamous Cell Carcinogenesis: New Insights

  2020cites this paper
• Do Laryngologists and General Otolaryngologists Manage Laryngopharyngeal Reflux Differently?

  2020cites this paper
• The role of bile reflux and its related NF-κB activated pathway in progression of hypopharyngeal squamous cell cancer.

  2020cites this paper
• Laryngopharyngeal reflux: The microbiota theory.

  2020cites this paper
• Management of Laryngopharyngeal Reflux Around the World: An International Study

  2020cites this paper
• Laryngopharyngeal reflux and head and neck cancers.

  2020cites this paper
• Laryngeal and Pharyngeal Squamous Cell Carcinoma After Antireflux Surgery in the 5 Nordic Countries

  2020cites this paper
• The temporal effects of topical NF-κB inhibition, in the in vivo prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model

  2020cites this paper