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dc.contributor.authorKELLEHER, DERMOT P
dc.contributor.authorWINDLE, HENRY
dc.date.accessioned2009-10-07T18:51:57Z
dc.date.available2009-10-07T18:51:57Z
dc.date.issued2004
dc.date.submitted2004en
dc.identifier.citationM. M. Abdel-Latif, J. O'Riordan, H. J. Windle, E. Carton, N. Ravi, D. Kelleher and J. V. Reynolds `NF-kappaB Activation in Esophageal Adenocarcinoma: Relationship to Barrett's Metaplasia, Survival, and Response to Neoadjuvant Chemoradiotherapy? in Annals of Surgery, 239, (4), 2004, pp 491-500en
dc.identifier.otherYen
dc.identifier.otherY
dc.identifier.other21311
dc.identifier.urihttp://hdl.handle.net/2262/33843
dc.descriptionPUBLISHEDen
dc.description.abstractOBJECTIVE: To examine the expression of the transcription factor nuclear factor kappa B (NF-kappaB) in Barrett's epithelium and adenocarcinoma and the impact of NF-kappaB expression on tumor stage and response to neoadjuvant chemotherapy and radiation therapy. SUMMARY BACKGROUND DATA: Progression of Barrett's esophagus to adenocarcinoma is associated with a wide range of cellular and molecular abnormalities. Nuclear factor-kappa B (NF-kappaB) regulates several genes involved in inflammatory, immune and apoptotic responses, but its role in esophageal inflammation and tumorigenesis has not been reported. METHODS: Mobility shift assay was used to measure NF-kappaB activity in nuclear extracts of fresh-frozen biopsies from tumor and uninvolved tissues (n = 30) and esophageal cell lines OE33, SKGT-4, and OE21. RelA expression was assessed by immunohistochemical staining (n = 97). The NF-kappaB/RelA and IkappaB protein expressions were also examined by Western blotting. RESULTS: NF-kappaB was not expressed in normal esophageal squamous epithelium, in contrast to increased expression in 40% of patients with Barrett's epithelium. Sixty-one percent of resected tumors (n = 97) displayed NF-kappaB immunoreactivity, and 87.5% of the NF-kappaB-positive tumors were Stage IIb and III compared with only 12.5% of patients with Stage I and IIa disease (P < 0.05). The expression of NF-kappaB inversely correlated with major or complete pathologic responses to neoadjuvant chemotherapy and radiation therapy, with 15/20 (75%) responders in the NF-kappaB-negative group compared with 7/38 (18%) in the NF-kappaB-positive group (P < 0.00001). Moreover, incubation of esophageal cell lines OE33, SKGT-4, and OE21 with deoxycholic acid or low pH induced NF-kappaB expression. CONCLUSIONS: Bile acids and low pH induce NF-kappaB expression in esophageal cell lines. NF-kappaB activation is common in esophageal adenocarcinoma. In patients with Barrett's epithelium and an associated esophageal adenocarcinoma, there is a progressive expression of NF-kappaB through Barrett's tumorigenesis. The absence of NF-kappaB expression in esophageal adenocarcinoma correlates with response to neoadjuvant chemoradiotherapy and may be of value in predicting response to neoadjuvant therapy.en
dc.description.sponsorshipSupported in part by the Baggot Street Research Fund.en
dc.format.extent491-500en
dc.format.extent1992042 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.ispartofseriesAnnals of Surgeryen
dc.relation.ispartofseries239en
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectClinical Medicineen
dc.titleNF-kappaB Activation in Esophageal Adenocarcinoma: Relationship to Barrett's Metaplasia, Survival, and Response to Neoadjuvant Chemoradiotherapyen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kellehdp
dc.identifier.rssinternalid21311
dc.identifier.rssurihttp://dx.doi.org/10.1097/01.sla.0000118751.95179.c6


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