{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:30:37Z","timestamp":1777426237031,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T00:00:00Z","timestamp":1434326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Otol Rhinol Laryngol"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Normal and Barrett\u2019s biopsies from 8 Barrett\u2019s esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg\/mL; 1-20 hours), acid (pH 4) \u00b1 pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Pepsin was detected in all 8 Barrett\u2019s and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett\u2019s, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1\u03b2 expression and cell migration in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Pepsin is synthesized by metaplastic, Barrett\u2019s esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0003489415590657","type":"journal-article","created":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T23:00:25Z","timestamp":1434409225000},"page":"893-902","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Local Synthesis of Pepsin in Barrett\u2019s Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma"],"prefix":"10.1177","volume":"124","author":[{"given":"Tina","family":"Samuels","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Hoekzema","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Goldblatt","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Frelich","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Bosler","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Hyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikki","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"bibr1-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.015"},{"key":"bibr2-0003489415590657","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i34.5598"},{"key":"bibr3-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.30297"},{"key":"bibr4-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcn035"},{"key":"bibr5-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02454.x"},{"key":"bibr6-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1G703"},{"key":"bibr7-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn211"},{"key":"bibr8-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.2011.174"},{"key":"bibr9-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12693"},{"key":"bibr10-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-014-2817-3"},{"key":"bibr11-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1080\/00365520701452209"},{"key":"bibr12-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.066209"},{"key":"bibr13-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/0194599813517862"},{"key":"bibr14-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23307"},{"key":"bibr15-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/000348941011900808"},{"key":"bibr16-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911800913"},{"key":"bibr17-0003489415590657","first-page":"1","volume-title":"Conference held in conjunction with the 9th International Symposium on Human Pepsin (ISHP)","volume":"33","author":"Pearson JP","year":"2011"},{"key":"bibr18-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24952"},{"key":"bibr19-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111001203"},{"key":"bibr20-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e318064f177"},{"key":"bibr21-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2009.08.022"},{"key":"bibr22-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/000348940711601211"},{"key":"bibr23-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.24840"},{"key":"bibr24-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1988.tb02842.x"},{"key":"bibr25-0003489415590657","first-page":"49","volume-title":"Barrett\u2019s Esophagus: Pathophysiology, Diagnosis and Management","author":"Mangla J","year":"1985"},{"key":"bibr26-0003489415590657","first-page":"186","volume-title":"The Esophageal Mucosa: Epidemiology. Proceedings from the World Organization for Specialized Studies on Diseases of the Esophagus; Paris, France","author":"Kahrilas P.","year":"2004"},{"key":"bibr27-0003489415590657","first-page":"208","volume-title":"The Esophageal Mucosa: Epidemiology. Proceedings from the World Organization for Specialized Studies on Diseases of the Esophagus; Paris, France","author":"Antoniolo D.","year":"2004"},{"key":"bibr28-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1177\/000348940611500108"},{"key":"bibr29-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.3.316"},{"key":"bibr30-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-539"},{"key":"bibr31-0003489415590657","first-page":"5767","volume":"60","author":"Souza RF","year":"2000","journal-title":"Cancer Res"},{"key":"bibr32-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh340"},{"key":"bibr33-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.34244"},{"key":"bibr34-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0528"},{"key":"bibr35-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.01005.x"},{"key":"bibr36-0003489415590657","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2023"}],"container-title":["Annals of Otology, Rhinology &amp; Laryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0003489415590657","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0003489415590657","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0003489415590657","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:30:51Z","timestamp":1777375851000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0003489415590657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,15]]},"references-count":36,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1177\/0003489415590657"],"URL":"https:\/\/doi.org\/10.1177\/0003489415590657","relation":{},"ISSN":["0003-4894","1943-572X"],"issn-type":[{"value":"0003-4894","type":"print"},{"value":"1943-572X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,15]]}}}