dc.contributor.author | KELLEHER, DERMOT P | |
dc.contributor.author | WINDLE, HENRY | |
dc.date.accessioned | 2009-10-07T18:51:57Z | |
dc.date.available | 2009-10-07T18:51:57Z | |
dc.date.issued | 2004 | |
dc.date.submitted | 2004 | en |
dc.identifier.citation | M. 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 491-500 | en |
dc.identifier.other | Y | en |
dc.identifier.other | Y | |
dc.identifier.other | 21311 | |
dc.description | PUBLISHED | en |
dc.description.abstract | OBJECTIVE: 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.sponsorship | Supported in part by the Baggot Street Research Fund. | en |
dc.format.extent | 491-500 | en |
dc.format.extent | 1992042 bytes | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | en |
dc.publisher | Lippincott Williams & Wilkins | en |
dc.relation.ispartofseries | Annals of Surgery | en |
dc.relation.ispartofseries | 239 | en |
dc.relation.ispartofseries | 4 | en |
dc.rights | Y | en |
dc.subject | Clinical Medicine | en |
dc.title | NF-kappaB Activation in Esophageal Adenocarcinoma: Relationship to Barrett's Metaplasia, Survival, and Response to Neoadjuvant Chemoradiotherapy | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/kellehdp | |
dc.identifier.rssinternalid | 21311 | |
dc.identifier.rssuri | http://dx.doi.org/10.1097/01.sla.0000118751.95179.c6 | |
dc.identifier.uri | http://hdl.handle.net/2262/33843 | |