{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:05:19Z","timestamp":1787018719328,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T00:00:00Z","timestamp":1388102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec>\n                    <jats:title>Outcome Objectives<\/jats:title>\n                    <jats:p>(1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony\u2010forming ability in hypopharyngeal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Translation research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Academic research laboratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01\u00a0mg\/mL, 0.1\u00a0mg\/mL, or 1\u00a0mg\/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin\u2010exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony\u2010forming ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An increased rate of relative wound density was observed in chronic pepsin\u2010treated (0.01\u00a0mg\/mL, 0.1\u00a0mg\/mL) cells compared with control (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;. 001), suggesting greater rates of cell migration. Pepsin\u2010treated (0.1\u00a0mg\/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1\u00a0mg\/mL, 1\u00a0mg\/mL) was associated with a dose\u2010dependent increase in colony\u2010forming ability relative to control (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;. 001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony\u2010forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0194599813517862","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T21:32:47Z","timestamp":1388179967000},"page":"618-624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Chronic Pepsin Exposure Promotes Anchorage\u2010Independent Growth and Migration of a Hypopharyngeal Squamous Cell Line"],"prefix":"10.1002","volume":"150","author":[{"given":"Elizabeth A.","family":"Kelly","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina 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