1,729
Views
34
CrossRef citations to date
0
Altmetric
Review

Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction

, &
Pages 782-795 | Received 11 Jun 2013, Accepted 11 Jun 2013, Published online: 17 Jun 2013

References

  • Crane SJ, Locke GR 3rd, Harmsen WS, Zinsmeister AR, Romero Y, Talley NJ. Survival trends in patients with gastric and esophageal adenocarcinomas: a population-based study. Mayo Clin Proc 2008; 83:1087 - 94; http://dx.doi.org/10.4065/83.10.1087; PMID: 18828967
  • Bouvier AM, Binquet C, Gagnaire A, Jouve JL, Faivre J, Bedenne L. Management and prognosis of esophageal cancers: has progress been made?. Eur J Cancer 2006; 42:228 - 33; http://dx.doi.org/10.1016/j.ejca.2005.08.038; PMID: 16337786
  • Younes M, Henson DE, Ertan A, Miller CC. Incidence and survival trends of esophageal carcinoma in the United States: racial and gender differences by histological type. Scand J Gastroenterol 2002; 37:1359 - 65; http://dx.doi.org/10.1080/003655202762671215; PMID: 12523583
  • Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97:142 - 6; http://dx.doi.org/10.1093/jnci/dji024; PMID: 15657344
  • Lagergren J, Mattsson F. No further increase in the incidence of esophageal adenocarcinoma in Sweden. Int J Cancer 2011; 129:513 - 6; http://dx.doi.org/10.1002/ijc.25701; PMID: 20878977
  • Pohl H, Sirovich B, Welch HG. Esophageal adenocarcinoma incidence: are we reaching the peak?. Cancer Epidemiol Biomarkers Prev 2010; 19:1468 - 70; http://dx.doi.org/10.1158/1055-9965.EPI-10-0012; PMID: 20501776
  • Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of malignant progression in Barrett esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011; 103:1049 - 57; http://dx.doi.org/10.1093/jnci/djr203; PMID: 21680910
  • Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett esophagus. N Engl J Med 2011; 365:1375 - 83; http://dx.doi.org/10.1056/NEJMoa1103042; PMID: 21995385
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646 - 74; http://dx.doi.org/10.1016/j.cell.2011.02.013; PMID: 21376230
  • Rabinovitch PS, Reid BJ, Haggitt RC, Norwood TH, Rubin CE. Progression to cancer in Barrett esophagus is associated with genomic instability. Lab Invest 1989; 60:65 - 71; PMID: 2911184
  • Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998; 396:643 - 9; http://dx.doi.org/10.1038/25292; PMID: 9872311
  • Zhang HY, Hormi-Carver K, Zhang X, Spechler SJ, Souza RF. In Benign Barrett's Epithelial Cells, Acid Exposure Generates Reactive Oxygen Species That Cause DNA Double-Strand Breaks. Cancer Res 2009.
  • Dvorak K, Payne CM, Chavarria M, Ramsey L, Dvorakova B, Bernstein H, et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett oesophagus. Gut 2007; 56:763 - 71; http://dx.doi.org/10.1136/gut.2006.103697; PMID: 17145738
  • Clemons NJ, McColl KE, Fitzgerald RC. Nitric oxide and acid induce double-strand DNA breaks in Barrett esophagus carcinogenesis via distinct mechanisms. Gastroenterology 2007; 133:1198 - 209; http://dx.doi.org/10.1053/j.gastro.2007.06.061; PMID: 17919494
  • Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, Stewart C, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet 2013; 45:478 - 86; http://dx.doi.org/10.1038/ng.2591; PMID: 23525077
  • Kaz AM, Wong CJ, Luo Y, Virgin JB, Washington MK, Willis JE, et al. DNA methylation profiling in Barrett esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses. Epigenetics 2011; 6:1403 - 12; http://dx.doi.org/10.4161/epi.6.12.18199; PMID: 22139570
  • Alvarez H, Opalinska J, Zhou L, Sohal D, Fazzari MJ, Yu Y, et al. Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis. PLoS Genet 2011; 7:e1001356; http://dx.doi.org/10.1371/journal.pgen.1001356; PMID: 21483804
  • El-Rifai W, Frierson HF Jr., Moskaluk CA, Harper JC, Petroni GR, Bissonette EA, et al. Genetic differences between adenocarcinomas arising in Barrett esophagus and gastric mucosa. Gastroenterology 2001; 121:592 - 8; http://dx.doi.org/10.1053/gast.2001.27215; PMID: 11522743
  • Lehmann K, Schneider PM. Differences in the molecular biology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third. Recent Results Cancer Res 2010; 182:65 - 72; http://dx.doi.org/10.1007/978-3-540-70579-6_5; PMID: 20676871
  • Reid BJ. Early events during neoplastic progression in Barrett esophagus. Cancer Biomark 2010; 9:307 - 24; PMID: 22112482
  • Maley CC, Galipeau PC, Finley JC, Wongsurawat VJ, Li X, Sanchez CA, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet 2006; 38:468 - 73; http://dx.doi.org/10.1038/ng1768; PMID: 16565718
  • Merlo LM, Shah NA, Li X, Blount PL, Vaughan TL, Reid BJ, et al. A comprehensive survey of clonal diversity measures in Barrett esophagus as biomarkers of progression to esophageal adenocarcinoma. Cancer Prev Res (Phila) 2010; 3:1388 - 97; http://dx.doi.org/10.1158/1940-6207.CAPR-10-0108; PMID: 20947487
  • Leedham SJ, Preston SL, McDonald SA, Elia G, Bhandari P, Poller D, et al. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett oesophagus. Gut 2008; 57:1041 - 8; http://dx.doi.org/10.1136/gut.2007.143339; PMID: 18305067
  • Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, et al. Fields of aberrant CpG island hypermethylation in Barrett esophagus and associated adenocarcinoma. Cancer Res 2000; 60:5021 - 6; PMID: 11016622
  • Phillips WA, Lord RV, Nancarrow DJ, Watson DI, Whiteman DC. Barrett esophagus. J Gastroenterol Hepatol 2011; 26:639 - 48; http://dx.doi.org/10.1111/j.1440-1746.2010.06602.x; PMID: 21166712
  • Weinstein IB, Joe A. Oncogene addiction. Cancer Res 2008; 68:3077 - 80, discussion 3080; http://dx.doi.org/10.1158/0008-5472.CAN-07-3293; PMID: 18451130
  • Quante M, Bhagat G, Abrams JA, Marache F, Good P, Lee MD, et al. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 2012; 21:36 - 51; http://dx.doi.org/10.1016/j.ccr.2011.12.004; PMID: 22264787
  • Boonstra JJ, van Marion R, Beer DG, Lin L, Chaves P, Ribeiro C, et al. Verification and unmasking of widely used human esophageal adenocarcinoma cell lines. J Natl Cancer Inst 2010; 102:271 - 4; http://dx.doi.org/10.1093/jnci/djp499; PMID: 20075370
  • Zhang X, Yu C, Wilson K, Zhang HY, Melton SD, Huo X, et al. Malignant transformation of non-neoplastic Barrett epithelial cells through well-defined genetic manipulations. PLoS One 2010; 5:5; PMID: 20927195
  • Kong J, Crissey MA, Stairs DB, Sepulveda AR, Lynch JP. Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions. Neoplasia 2011; 13:792 - 805; PMID: 21969813
  • Kosoff RE, Gardiner KL, Merlo LM, Pavlov K, Rustgi AK, Maley CC. Development and characterization of an organotypic model of Barrett esophagus. J Cell Physiol 2012; 227:2654 - 9; http://dx.doi.org/10.1002/jcp.23007; PMID: 21882191
  • Sato T, Stange DE, Ferrante M, Vries RGJ, Van Es JH, Van den Brink S, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett epithelium. Gastroenterology 2011; 141:1762 - 72; http://dx.doi.org/10.1053/j.gastro.2011.07.050; PMID: 21889923
  • Croagh D, Cheng S, Tikoo A, Nandurkar S, Thomas RJ, Kaur P, et al. Reconstitution of stratified murine and human oesophageal epithelia in an in vivo transplant culture system. Scand J Gastroenterol 2008; 43:1158 - 68; http://dx.doi.org/10.1080/00365520802102489; PMID: 18609138
  • Gros SJ. Orthotopic models of esophageal carcinoma and their use in drug discovery. Curr Protoc Pharmacol 2011; Chapter 14:Unit14 20.
  • Jankowski J, Coghill G, Tregaskis B, Hopwood D, Wormsley KG. Epidermal growth factor in the oesophagus. Gut 1992; 33:1448 - 53; http://dx.doi.org/10.1136/gut.33.11.1448; PMID: 1452065
  • Jankowski J, McMenemin R, Hopwood D, Penston J, Wormsley KG. Abnormal expression of growth regulatory factors in Barrett oesophagus. Clin Sci (Lond) 1991; 81:663 - 8; PMID: 1661653
  • Jankowski J, McMenemin R, Yu C, Hopwood D, Wormsley KG. Proliferating cell nuclear antigen in oesophageal diseases; correlation with transforming growth factor alpha expression. Gut 1992; 33:587 - 91; http://dx.doi.org/10.1136/gut.33.5.587; PMID: 1351861
  • Menke V, Pot RG, Moons LM, van Zoest KP, Hansen B, van Dekken H, et al. Functional single-nucleotide polymorphism of epidermal growth factor is associated with the development of Barrett esophagus and esophageal adenocarcinoma. J Hum Genet 2012; 57:26 - 32; http://dx.doi.org/10.1038/jhg.2011.124; PMID: 22129558
  • Lanuti M, Liu G, Goodwin JM, Zhai R, Fuchs BC, Asomaning K, et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res 2008; 14:3216 - 22; http://dx.doi.org/10.1158/1078-0432.CCR-07-4932; PMID: 18483390
  • Yacoub L, Goldman H, Odze RD. Transforming growth factor-alpha, epidermal growth factor receptor, and MiB-1 expression in Barrett-associated neoplasia: correlation with prognosis. Mod Pathol 1997; 10:105 - 12; PMID: 9127315
  • Wilkinson NW, Black JD, Roukhadze E, Driscoll D, Smiley S, Hoshi H, et al. Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma. J Gastrointest Surg 2004; 8:448 - 53; http://dx.doi.org/10.1016/j.gassur.2004.01.006; PMID: 15120370
  • Friess H, Fukuda A, Tang WH, Eichenberger A, Furlan N, Zimmermann A, et al. Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer: overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. World J Surg 1999; 23:1010 - 8; http://dx.doi.org/10.1007/s002689900616; PMID: 10512940
  • Wang KL, Wu TT, Choi IS, Wang H, Resetkova E, Correa AM, et al. Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Cancer 2007; 109:658 - 67; http://dx.doi.org/10.1002/cncr.22445; PMID: 17211865
  • Gibson MK, Abraham SC, Wu TT, Burtness B, Heitmiller RF, Heath E, et al. Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clin Cancer Res 2003; 9:6461 - 8; PMID: 14695149
  • Rygiel AM, Milano F, Ten Kate FJ, Schaap A, Wang KK, Peppelenbosch MP, et al. Gains and amplifications of c-myc, EGFR, and 20.q13 loci in the no dysplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus. Cancer Epidemiol Biomarkers Prev 2008; 17:1380 - 5; http://dx.doi.org/10.1158/1055-9965.EPI-07-2734; PMID: 18559552
  • al-Kasspooles M, Moore JH, Orringer MB, Beer DG. Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. Int J Cancer 1993; 54:213 - 9; http://dx.doi.org/10.1002/ijc.2910540209; PMID: 8098013
  • Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006; 12:4283 - 7; http://dx.doi.org/10.1158/1078-0432.CCR-06-0189; PMID: 16857803
  • Ohashi S, Natsuizaka M, Wong GS, Michaylira CZ, Grugan KD, Stairs DB, et al. Epidermal growth factor receptor and mutant p53 expand an esophageal cellular subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription factors. Cancer Res 2010; 70:4174 - 84; http://dx.doi.org/10.1158/0008-5472.CAN-09-4614; PMID: 20424117
  • Dahlberg PS, Jacobson BA, Dahal G, Fink JM, Kratzke RA, Maddaus MA, et al. ERBB2 amplifications in esophageal adenocarcinoma. Ann Thorac Surg 2004; 78:1790 - 800; http://dx.doi.org/10.1016/j.athoracsur.2004.05.037; PMID: 15511476
  • Walch A, Specht K, Braselmann H, Stein H, Siewert JR, Hopt U, et al. Coamplification and coexpression of GRB7 and ERBB2 is found in high grade intraepithelial neoplasia and in invasive Barrett carcinoma. Int J Cancer 2004; 112:747 - 53; http://dx.doi.org/10.1002/ijc.20411; PMID: 15386389
  • Reichelt U, Duesedau P, Tsourlakis MCh, Quaas A, Link BC, Schurr PG, et al. Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus. Mod Pathol 2007; 20:120 - 9; http://dx.doi.org/10.1038/modpathol.3800712; PMID: 17143264
  • Rossi E, Villanacci V, Bassotti G, Casa DD, Missale G, Minelli L, et al. Her-2/neu in barrett esophagus: a comparative study between histology, immunohistochemistry, and fluorescence in situ hybridization. Diagn Mol Pathol 2006; 15:125 - 30; http://dx.doi.org/10.1097/01.pdm.0000213455.22527.f7; PMID: 16932066
  • Brien TP, Odze RD, Sheehan CE, McKenna BJ, Ross JS. HER-2/neu gene amplification by FISH predicts poor survival in Barrett esophagus-associated adenocarcinoma. Hum Pathol 2000; 31:35 - 9; http://dx.doi.org/10.1016/S0046-8177(00)80195-1; PMID: 10665910
  • Thompson SK, Sullivan TR, Davies R, Ruszkiewicz AR. Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival. Ann Surg Oncol 2011; 18:2010 - 7; http://dx.doi.org/10.1245/s10434-011-1554-1; PMID: 21267790
  • Hu Y, Bandla S, Godfrey TE, Tan D, Luketich JD, Pennathur A, et al. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma. Mod Pathol 2011; 24:899 - 907; http://dx.doi.org/10.1038/modpathol.2011.47; PMID: 21460800
  • Mukherjee K, Chakravarthy AB, Goff LW, El-Rifai W. Esophageal adenocarcinoma: treatment modalities in the era of targeted therapy. Dig Dis Sci 2010; 55:3304 - 14; http://dx.doi.org/10.1007/s10620-010-1187-4; PMID: 20300841
  • Lord RV, O’Grady R, Sheehan C, Field AF, Ward RL. K-ras codon 12 mutations in Barrett oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction. J Gastroenterol Hepatol 2000; 15:730 - 6; http://dx.doi.org/10.1046/j.1440-1746.2000.02163.x; PMID: 10937677
  • Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al, ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376:687 - 97; http://dx.doi.org/10.1016/S0140-6736(10)61121-X; PMID: 20728210
  • Möbius C, Stein HJ, Becker I, Feith M, Theisen J, Gais P, et al. The ‘angiogenic switch’ in the progression from Barrett metaplasia to esophageal adenocarcinoma. Eur J Surg Oncol 2003; 29:890 - 4; http://dx.doi.org/10.1016/j.ejso.2003.07.002; PMID: 14624783
  • Couvelard A, Paraf F, Gratio V, Scoazec JY, Hénin D, Degott C, et al. Angiogenesis in the neoplastic sequence of Barrett oesophagus. Correlation with VEGF expression. J Pathol 2000; 192:14 - 8; http://dx.doi.org/10.1002/1096-9896(2000)9999:9999<::AID-PATH709>3.0.CO;2-F; PMID: 10951394
  • Lord RV, Park JM, Wickramasinghe K, DeMeester SR, Oberg S, Salonga D, et al. Vascular endothelial growth factor and basic fibroblast growth factor expression in esophageal adenocarcinoma and Barrett esophagus. J Thorac Cardiovasc Surg 2003; 125:246 - 53; http://dx.doi.org/10.1067/mtc.2003.203; PMID: 12579092
  • Griffiths EA, Pritchard SA, McGrath SM, Valentine HR, Price PM, Welch IM, et al. Increasing expression of hypoxia-inducible proteins in the Barrett metaplasia-dysplasia-adenocarcinoma sequence. Br J Cancer 2007; 96:1377 - 83; PMID: 17437013
  • Möbius C, Stein HJ, Becker I, Feith M, Theisen J, Gais P, et al. Vascular endothelial growth factor expression and neovascularization in Barrett carcinoma. World J Surg 2004; 28:675 - 9; http://dx.doi.org/10.1007/s00268-004-7286-7; PMID: 15175900
  • Millikan KW, Mall JW, Myers JA, Hollinger EF, Doolas A, Saclarides TJ. Do angiogenesis and growth factor expression predict prognosis of esophageal cancer?. Am Surg 2000; 66:401 - 5, discussion 405-6; PMID: 10776879
  • Auvinen MI, Sihvo EI, Ruohtula T, Salminen JT, Koivistoinen A, Siivola P, et al. Incipient angiogenesis in Barrett epithelium and lymphangiogenesis in Barrett adenocarcinoma. J Clin Oncol 2002; 20:2971 - 9; http://dx.doi.org/10.1200/JCO.2002.09.011; PMID: 12089227
  • Möbius C, Freire J, Becker I, Feith M, Brücher BL, Hennig M, et al. VEGF-C expression in squamous cell carcinoma and adenocarcinoma of the esophagus. World J Surg 2007; 31:1768 - 72, discussion 1773-4; http://dx.doi.org/10.1007/s00268-006-0373-1; PMID: 17354029
  • Neulen J, Yan Z, Raczek S, Weindel K, Keck C, Weich HA, et al. Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 1995; 80:1967 - 71; http://dx.doi.org/10.1210/jc.80.6.1967; PMID: 7775647
  • Couvelard A, Paraf F, Vidaud D, Dubois S, Vidaud M, Fléjou JF, et al. Human chorionic gonadotrophin beta expression in malignant Barrett oesophagus. Virchows Arch 2004; 445:279 - 84; http://dx.doi.org/10.1007/s00428-004-1078-1; PMID: 15309632
  • Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett esophagus and associated adenocarcinomas. Cancer Res 1998; 58:2929 - 34; PMID: 9679948
  • von Rahden BH, Stein HJ, Hartl SA, Theisen J, Stigler B, Siewert JR, et al. Expression of prostaglandin E synthase in Barrett cancer. Dis Esophagus 2008; 21:304 - 8; http://dx.doi.org/10.1111/j.1442-2050.2007.00801.x; PMID: 18477251
  • von Rahden BH, Stein HJ, Pühringer F, Koch I, Langer R, Piontek G, et al. Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A, VEGF-C) in esophageal adenocarcinoma. Cancer Res 2005; 65:5038 - 44; http://dx.doi.org/10.1158/0008-5472.CAN-04-1107; PMID: 15958546
  • Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G. Cyclooxygenase 2 expression in Barrett esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology 2000; 118:487 - 96; http://dx.doi.org/10.1016/S0016-5085(00)70254-X; PMID: 10702199
  • Lanas A, Ortego J, Sopeña F, Alcedo J, Barrio E, Bujanda L, et al. Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett oesophagus. Aliment Pharmacol Ther 2007; 26:913 - 23; http://dx.doi.org/10.1111/j.1365-2036.2007.03429.x; PMID: 17767476
  • Burnat G, Rau T, Elshimi E, Hahn EG, Konturek PC. Bile acids induce overexpression of homeobox gene CDX-2 and vascular endothelial growth factor (VEGF) in human Barrett esophageal mucosa and adenocarcinoma cell line. Scand J Gastroenterol 2007; 42:1460 - 5; http://dx.doi.org/10.1080/00365520701452209; PMID: 17852856
  • Zhai R, Liu G, Asomaning K, Su L, Kulke MH, Heist RS, et al. Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. Carcinogenesis 2008; 29:2330 - 4; http://dx.doi.org/10.1093/carcin/bgn210; PMID: 18780893
  • Chow WH, Blot WJ, Vaughan TL, Risch HA, Gammon MD, Stanford JL, et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1998; 90:150 - 5; http://dx.doi.org/10.1093/jnci/90.2.150; PMID: 9450576
  • Kamat P, Wen S, Morris J, Anandasabapathy S. Exploring the association between elevated body mass index and Barrett esophagus: a systematic review and meta-analysis. Ann Thorac Surg 2009; 87:655 - 62; http://dx.doi.org/10.1016/j.athoracsur.2008.08.003; PMID: 19161814
  • Corley DA, Kubo A, Levin TR, Block G, Habel L, Zhao W, et al. Abdominal obesity and body mass index as risk factors for Barrett esophagus. Gastroenterology 2007; 133:34 - 41, quiz 311; http://dx.doi.org/10.1053/j.gastro.2007.04.046; PMID: 17631128
  • Edelstein ZR, Farrow DC, Bronner MP, Rosen SN, Vaughan TL. Central adiposity and risk of Barrett esophagus. Gastroenterology 2007; 133:403 - 11; http://dx.doi.org/10.1053/j.gastro.2007.05.026; PMID: 17681161
  • Ryan AM, Healy LA, Power DG, Byrne M, Murphy S, Byrne PJ, et al. Barrett esophagus: prevalence of central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg 2008; 247:909 - 15; http://dx.doi.org/10.1097/SLA.0b013e3181612cac; PMID: 18520215
  • Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab 2006; 17:328 - 36; http://dx.doi.org/10.1016/j.tem.2006.08.006; PMID: 16956771
  • Di Martino E, Wild CP, Rotimi O, Darnton JS, Olliver RJ, Hardie LJ. IGFBP-3 and IGFBP-10 (CYR61) up-regulation during the development of Barrett oesophagus and associated oesophageal adenocarcinoma: potential biomarkers of disease risk. Biomarkers 2006; 11:547 - 61; http://dx.doi.org/10.1080/13547500600896791; PMID: 17056474
  • Greer KB, Thompson CL, Brenner L, Bednarchik B, Dawson D, Willis J, et al. Association of insulin and insulin-like growth factors with Barrett oesophagus. Gut 2012; 61:665 - 72; http://dx.doi.org/10.1136/gutjnl-2011-300641; PMID: 21930730
  • Siahpush SH, Vaughan TL, Lampe JN, Freeman R, Lewis S, Odze RD, et al. Longitudinal study of insulin-like growth factor, insulin-like growth factor binding protein-3, and their polymorphisms: risk of neoplastic progression in Barrett esophagus. Cancer Epidemiol Biomarkers Prev 2007; 16:2387 - 95; http://dx.doi.org/10.1158/1055-9965.EPI-06-0986; PMID: 18006928
  • Iravani S, Zhang HQ, Yuan ZQ, Cheng JQ, Karl RC, Jove R, et al. Modification of insulin-like growth factor 1 receptor, c-Src, and Bcl-XL protein expression during the progression of Barrett neoplasia. Hum Pathol 2003; 34:975 - 82; http://dx.doi.org/10.1053/S0046-8177(03)00354-X; PMID: 14608530
  • Kalinina T, Bockhorn M, Kaifi JT, Thieltges S, Güngör C, Effenberger KE, et al. Insulin-like growth factor-1 receptor as a novel prognostic marker and its implication as a cotarget in the treatment of human adenocarcinoma of the esophagus. Int J Cancer 2010; 127:1931 - 40; http://dx.doi.org/10.1002/ijc.25196; PMID: 20104520
  • Zhao R, Macdonald K, Casson AG. Insulin-like growth factor type I receptor gene expression and obesity in esophageal adenocarcinoma. Mol Carcinog 2009; 48:982 - 8; http://dx.doi.org/10.1002/mc.20562; PMID: 19582762
  • MacDonald K, Porter GA, Guernsey DL, Zhao R, Casson AG. A polymorphic variant of the insulin-like growth factor type I receptor gene modifies risk of obesity for esophageal adenocarcinoma. Cancer Epidemiol 2009; 33:37 - 40; http://dx.doi.org/10.1016/j.canep.2009.04.014; PMID: 19679045
  • Anderson MR, Harrison R, Atherfold PA, Campbell MJ, Darnton SJ, Obszynska J, et al. Met receptor signaling: a key effector in esophageal adenocarcinoma. Clin Cancer Res 2006; 12:5936 - 43; http://dx.doi.org/10.1158/1078-0432.CCR-06-1208; PMID: 17062664
  • Herrera LJ, El-Hefnawy T, Queiroz de Oliveira PE, Raja S, Finkelstein S, Gooding W, et al. The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia 2005; 7:75 - 84; http://dx.doi.org/10.1593/neo.04367; PMID: 15720819
  • Tuynman JB, Lagarde SM, Ten Kate FJ, Richel DJ, van Lanschot JJ. Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma. Br J Cancer 2008; 98:1102 - 8; http://dx.doi.org/10.1038/sj.bjc.6604251; PMID: 18349821
  • Miller CT, Lin L, Casper AM, Lim J, Thomas DG, Orringer MB, et al. Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma. Oncogene 2006; 25:409 - 18; PMID: 16186806
  • Hector A, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, et al. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther 2010; 10:1009 - 18; http://dx.doi.org/10.4161/cbt.10.10.13248; PMID: 20818175
  • Holland SJ, Pan A, Franci C, Hu Y, Chang B, Li W, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res 2010; 70:1544 - 54; http://dx.doi.org/10.1158/0008-5472.CAN-09-2997; PMID: 20145120
  • Paterson AL, Shannon NB, Lao-Sirieix P, Ong CA, Peters CJ, O’Donovan M, et al. A systematic approach to therapeutic target selection in oesophago-gastric cancer. Gut 2012; http://dx.doi.org/10.1136/gutjnl-2012-302039; PMID: 22773546
  • Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology 2001; 121:79 - 90; http://dx.doi.org/10.1053/gast.2001.25490; PMID: 11438496
  • Bråkenhielm E, Veitonmäki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A 2004; 101:2476 - 81; http://dx.doi.org/10.1073/pnas.0308671100; PMID: 14983034
  • Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer. Clin Cancer Res 2005; 11:466 - 72; PMID: 15701829
  • Otake S, Takeda H, Suzuki Y, Fukui T, Watanabe S, Ishihama K, et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res 2005; 11:3642 - 6; http://dx.doi.org/10.1158/1078-0432.CCR-04-1868; PMID: 15897559
  • Francois F, Roper J, Goodman AJ, Pei Z, Ghumman M, Mourad M, et al. The association of gastric leptin with oesophageal inflammation and metaplasia. Gut 2008; 57:16 - 24; http://dx.doi.org/10.1136/gut.2007.131672; PMID: 17761783
  • Kendall BJ, Macdonald GA, Hayward NK, Prins JB, Brown I, Walker N, et al, Study of Digestive Health. Leptin and the risk of Barrett oesophagus. Gut 2008; 57:448 - 54; http://dx.doi.org/10.1136/gut.2007.131243; PMID: 18178609
  • Thompson OM, Beresford SA, Kirk EA, Bronner MP, Vaughan TL. Serum leptin and adiponectin levels and risk of Barrett esophagus and intestinal metaplasia of the gastroesophageal junction. Obesity (Silver Spring) 2010; 18:2204 - 11; http://dx.doi.org/10.1038/oby.2009.508; PMID: 20111023
  • Rubenstein JH, Dahlkemper A, Kao JY, Zhang M, Morgenstern H, McMahon L, et al. A pilot study of the association of low plasma adiponectin and Barrett esophagus. Am J Gastroenterol 2008; 103:1358 - 64; http://dx.doi.org/10.1111/j.1572-0241.2008.01823.x; PMID: 18510610
  • Yildirim A, Bilici M, Cayir K, Yanmaz V, Yildirim S, Tekin SB. Serum adiponectin levels in patients with esophageal cancer. Jpn J Clin Oncol 2009; 39:92 - 6; http://dx.doi.org/10.1093/jjco/hyn143; PMID: 19116211
  • Konturek PC, Burnat G, Rau T, Hahn EG, Konturek S. Effect of adiponectin and ghrelin on apoptosis of Barrett adenocarcinoma cell line. Dig Dis Sci 2008; 53:597 - 605; http://dx.doi.org/10.1007/s10620-007-9922-1; PMID: 17763959
  • Ogunwobi O, Mutungi G, Beales IL. Leptin stimulates proliferation and inhibits apoptosis in Barrett esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-E2-mediated transactivation of the epidermal growth factor receptor and c-Jun NH2-terminal kinase activation. Endocrinology 2006; 147:4505 - 16; http://dx.doi.org/10.1210/en.2006-0224; PMID: 16740977
  • Beales IL, Ogunwobi OO. Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. Mol Cell Endocrinol 2007; 274:60 - 8; http://dx.doi.org/10.1016/j.mce.2007.05.017; PMID: 17618045
  • Ogunwobi OO, Beales IL. Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation. Mol Cell Endocrinol 2008; 285:43 - 50; http://dx.doi.org/10.1016/j.mce.2008.01.023; PMID: 18313838
  • Koliopanos A, Friess H, di Mola FF, Tang WH, Kubulus D, Brigstock D, et al. Connective tissue growth factor gene expression alters tumor progression in esophageal cancer. World J Surg 2002; 26:420 - 7; http://dx.doi.org/10.1007/s00268-001-0242-x; PMID: 11910473
  • von Rahden BH, Stein HJ, Feith M, Pühringer F, Theisen J, Siewert JR, et al. Overexpression of TGF-beta1 in esophageal (Barrett) adenocarcinoma is associated with advanced stage of disease and poor prognosis. Mol Carcinog 2006; 45:786 - 94; http://dx.doi.org/10.1002/mc.20259; PMID: 16921482
  • Rees JR, Onwuegbusi BA, Save VE, Alderson D, Fitzgerald RC. In vivo and in vitro evidence for transforming growth factor-beta1-mediated epithelial to mesenchymal transition in esophageal adenocarcinoma. Cancer Res 2006; 66:9583 - 90; http://dx.doi.org/10.1158/0008-5472.CAN-06-1842; PMID: 17018615
  • Barrett MT, Galipeau PC, Sanchez CA, Emond MJ, Reid BJ. Determination of the frequency of loss of heterozygosity in esophageal adenocarcinoma by cell sorting, whole genome amplification and microsatellite polymorphisms. Oncogene 1996; 12:1873 - 8; PMID: 8649847
  • Onwuegbusi BA, Aitchison A, Chin SF, Kranjac T, Mills I, Huang Y, et al. Impaired transforming growth factor beta signalling in Barrett carcinogenesis due to frequent SMAD4 inactivation. Gut 2006; 55:764 - 74; http://dx.doi.org/10.1136/gut.2005.076430; PMID: 16368780
  • Villanacci V, Bellone G, Battaglia E, Rossi E, Carbone A, Prati A, et al. Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett esophagus. Hum Pathol 2008; 39:403 - 9; http://dx.doi.org/10.1016/j.humpath.2007.07.009; PMID: 18261624
  • Soslow RA, Remotti H, Baergen RN, Altorki NK. Suppression of apoptosis does not foster neoplastic growth in Barrett esophagus. Mod Pathol 1999; 12:239 - 50; PMID: 10102608
  • Younes M, Schwartz MR, Finnie D, Younes A. Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett metaplasia of the esophagus. Hum Pathol 1999; 30:1309 - 13; http://dx.doi.org/10.1016/S0046-8177(99)90061-8; PMID: 10571510
  • Younes M, Lechago J, Ertan A, Finnie D, Younes A. Decreased expression of Fas (CD95/APO1) associated with goblet cell metaplasia in Barrett esophagus. Hum Pathol 2000; 31:434 - 8; http://dx.doi.org/10.1053/hp.2000.6715; PMID: 10821489
  • Bennett MW, O’Connell J, O’Sullivan GC, Brady C, Roche D, Collins JK, et al. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol 1998; 160:5669 - 75; PMID: 9605174
  • Watson GA, Naran S, Zhang X, Stang MT, Queiroz de Oliveira PE, Hughes SJ. Cytoplasmic overexpression of CD95L in esophageal adenocarcinoma cells overcomes resistance to CD95-mediated apoptosis. Neoplasia 2011; 13:198 - 205; PMID: 21390183
  • Popnikolov NK, Gatalica Z, Adegboyega PA, Norris BA, Pasricha PJ. Downregulation of TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L in Barrett esophagus with dysplasia and adenocarcinoma. Appl Immunohistochem Mol Morphol 2006; 14:161 - 5; http://dx.doi.org/10.1097/01.pai.0000157905.30872.9f; PMID: 16785783
  • Coppola D, Schreiber RH, Mora L, Dalton W, Karl RC. Significance of Fas and retinoblastoma protein expression during the progression of Barrett metaplasia to adenocarcinoma. Ann Surg Oncol 1999; 6:298 - 304; http://dx.doi.org/10.1007/s10434-999-0298-7; PMID: 10340890
  • Hughes SJ, Nambu Y, Soldes OS, Hamstra D, Rehemtulla A, Iannettoni MD, et al. Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma. Cancer Res 1997; 57:5571 - 8; PMID: 9407969
  • Naran S, Abrams P, de Oliveira PQ, Hughes SJ. Bile salts differentially sensitize esophageal squamous cells to CD95 (Fas/Apo-1 receptor) mediated apoptosis. J Surg Res 2011; 171:504 - 9; http://dx.doi.org/10.1016/j.jss.2010.05.001; PMID: 20934723
  • Peng D, Sheta EA, Powell SM, Moskaluk CA, Washington K, Goldknopf IL, et al. Alterations in Barrett-related adenocarcinomas: a proteomic approach. Int J Cancer 2008; 122:1303 - 10; http://dx.doi.org/10.1002/ijc.23258; PMID: 18000824
  • Liu CY, Wu MC, Chen F, Ter-Minassian M, Asomaning K, Zhai R, et al. A Large-scale genetic association study of esophageal adenocarcinoma risk. Carcinogenesis 2010; 31:1259 - 63; http://dx.doi.org/10.1093/carcin/bgq092; PMID: 20453000
  • Wu I-C, Zhao Y, Zhai R, Liu CY, Chen F, Ter-Minassian M, et al. Interactions between genetic polymorphisms in the apoptotic pathway and environmental factors on esophageal adenocarcinoma risk. Carcinogenesis 2011; 32:502 - 6; http://dx.doi.org/10.1093/carcin/bgq287; PMID: 21212151
  • Goldblum JR, Rice TW. bcl-2 protein expression in the Barrett metaplasia-dysplasia-carcinoma sequence. Mod Pathol 1995; 8:866 - 9; PMID: 8552577
  • Katada N, Hinder RA, Smyrk TC, Hirabayashi N, Perdikis G, Lund RJ, et al. Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus. Arch Surg 1997; 132:728 - 33; http://dx.doi.org/10.1001/archsurg.1997.01430310042007; PMID: 9230856
  • Rioux-Leclercq N, Turlin B, Sutherland F, Heresbach N, Launois B, Campion JP, et al. Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett esophagus. Oncol Rep 1999; 6:877 - 82; PMID: 10373674
  • Lauwers GY, Kandemir O, Kubilis PS, Scott GV. Cellular kinetics in Barrett epithelium carcinogenic sequence: roles of apoptosis, bcl-2 protein, and cellular proliferation. Mod Pathol 1997; 10:1201 - 8; PMID: 9436964
  • Raouf AA, Evoy DA, Carton E, Mulligan E, Griffin MM, Reynolds JV. Loss of Bcl-2 expression in Barrett dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation. Dis Esophagus 2003; 16:17 - 23; http://dx.doi.org/10.1046/j.1442-2050.2003.00281.x; PMID: 12581249
  • van der Woude CJ, Jansen PL, Tiebosch AT, Beuving A, Homan M, Kleibeuker JH, et al. Expression of apoptosis-related proteins in Barrett metaplasia-dysplasia-carcinoma sequence: a switch to a more resistant phenotype. Hum Pathol 2002; 33:686 - 92; http://dx.doi.org/10.1053/hupa.2002.124908; PMID: 12196918
  • Galiana C, Lozano JC, Bancel B, Nakazawa H, Yamasaki H. High frequency of Ki-ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus. Mol Carcinog 1995; 14:286 - 93; http://dx.doi.org/10.1002/mc.2940140409; PMID: 8519418
  • Trautmann B, Wittekind C, Strobel D, Meixner H, Keymling J, Gossner L, et al. K-ras point mutations are rare events in premalignant forms of Barrett oesophagus. Eur J Gastroenterol Hepatol 1996; 8:799 - 804; PMID: 8864678
  • Sommerer F, Vieth M, Markwarth A, Röhrich K, Vomschloss S, May A, et al. Mutations of BRAF and KRAS2 in the development of Barrett adenocarcinoma. Oncogene 2004; 23:554 - 8; http://dx.doi.org/10.1038/sj.onc.1207189; PMID: 14724583
  • Phillips WA, Russell SE, Ciavarella ML, Choong DY, Montgomery KG, Smith K, et al. Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett esophagus. Int J Cancer 2006; 118:2644 - 6; http://dx.doi.org/10.1002/ijc.21706; PMID: 16380997
  • Miller CT, Moy JR, Lin L, Schipper M, Normolle D, Brenner DE, et al. Gene amplification in esophageal adenocarcinomas and Barrett with high-grade dysplasia. Clin Cancer Res 2003; 9:4819 - 25; PMID: 14581353
  • Beales IL, Ogunwobi O, Cameron E, El-Amin K, Mutungi G, Wilkinson M. Activation of Akt is increased in the dysplasia-carcinoma sequence in Barrett oesophagus and contributes to increased proliferation and inhibition of apoptosis: a histopathological and functional study. BMC Cancer 2007; 7:97; http://dx.doi.org/10.1186/1471-2407-7-97; PMID: 17559672
  • Sagatys E, Garrett CR, Boulware D, Kelley S, Malafa M, Cheng JQ, et al. Activation of the serine/threonine protein kinase Akt during the progression of Barrett neoplasia. Hum Pathol 2007; 38:1526 - 31; http://dx.doi.org/10.1016/j.humpath.2007.03.003; PMID: 17640711
  • Mariette C, Piessen G, Leteurtre E, Hémon B, Triboulet JP, Van Seuningen I. Activation of MUC1 mucin expression by bile acids in human esophageal adenocarcinomatous cells and tissues is mediated by the phosphatidylinositol 3-kinase. Surgery 2008; 143:58 - 71; http://dx.doi.org/10.1016/j.surg.2007.07.043; PMID: 18154934
  • Mariette C, Perrais M, Leteurtre E, Jonckheere N, Hémon B, Pigny P, et al. Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway. Biochem J 2004; 377:701 - 8; http://dx.doi.org/10.1042/BJ20031132; PMID: 14583090
  • Zhang F, Altorki NK, Wu YC, Soslow RA, Subbaramaiah K, Dannenberg AJ. Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids. Gastroenterology 2001; 121:1391 - 9; http://dx.doi.org/10.1053/gast.2001.29781; PMID: 11729118
  • Song S, Byrd JC, Guha S, Liu K-F, Koul D, Bresalier RS. Induction of MUC5AC mucin by conjugated bile acids in the esophagus involves the phosphatidylinositol 3-kinase/protein kinase C/activator protein-1 pathway. Cancer 2010; 117:2386 - 97; http://dx.doi.org/10.1002/cncr.25796; PMID: 21157954
  • Ogunwobi OO, Beales IL. Glycine-extended gastrin stimulates proliferation via JAK2- and Akt-dependent NF-kappaB activation in Barrett oesophageal adenocarcinoma cells. Mol Cell Endocrinol 2008; 296:94 - 102; http://dx.doi.org/10.1016/j.mce.2008.08.004; PMID: 18771702
  • Harris JC, Clarke PA, Awan A, Jankowski J, Watson SA. An antiapoptotic role for gastrin and the gastrin/CCK-2 receptor in Barrett esophagus. Cancer Res 2004; 64:1915 - 9; http://dx.doi.org/10.1158/0008-5472.CAN-03-2713; PMID: 15026323
  • Song S, Guha S, Liu K, Buttar NS, Bresalier RS. COX-2 induction by unconjugated bile acids involves reactive oxygen species-mediated signalling pathways in Barrett oesophagus and oesophageal adenocarcinoma. Gut 2007; 56:1512 - 21; http://dx.doi.org/10.1136/gut.2007.121244; PMID: 17604323
  • Morris CD, Armstrong GR, Bigley G, Green H, Attwood SE. Cyclooxygenase-2 expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001; 96:990 - 6; PMID: 11316217
  • Botelho NK, Schneiders FI, Lord SJ, Freeman AK, Tyagi S, Nancarrow DJ, et al. Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues. Cancer Biol Ther 2010; 10:172 - 9; http://dx.doi.org/10.4161/cbt.10.2.12166; PMID: 20543560
  • Möbius C, Stein HJ, Spiess C, Becker I, Feith M, Theisen J, et al. COX2 expression, angiogenesis, proliferation and survival in Barrett cancer. Eur J Surg Oncol 2005; 31:755 - 9; http://dx.doi.org/10.1016/j.ejso.2005.01.006; PMID: 15979837
  • Abdalla SI, Sanderson IR, Fitzgerald RC. Effect of inflammation on cyclooxygenase (COX)-2 expression in benign and malignant oesophageal cells. Carcinogenesis 2005; 26:1627 - 33; http://dx.doi.org/10.1093/carcin/bgi114; PMID: 15878911
  • Zhang F, Subbaramaiah K, Altorki N, Dannenberg AJ. Dihydroxy bile acids activate the transcription of cyclooxygenase-2. J Biol Chem 1998; 273:2424 - 8; http://dx.doi.org/10.1074/jbc.273.4.2424; PMID: 9442092
  • Looby E, Abdel-Latif MM, Athié-Morales V, Duggan S, Long A, Kelleher D. Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells. BMC Cancer 2009; 9:190; http://dx.doi.org/10.1186/1471-2407-9-190; PMID: 19534809
  • Benoit V, de Moraes E, Dar NA, Taranchon E, Bours V, Hautefeuille A, et al. Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB. Oncogene 2006; 25:5708 - 18; http://dx.doi.org/10.1038/sj.onc.1209579; PMID: 16682957
  • Moons LM, Kuipers EJ, Rygiel AM, Groothuismink AZ, Geldof H, Bode WA, et al. COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma. Am J Gastroenterol 2007; 102:2373 - 9; http://dx.doi.org/10.1111/j.1572-0241.2007.01373.x; PMID: 17581270
  • Kristinsson JO, van Westerveld P, te Morsche RH, Roelofs HM, Wobbes T, Witteman BJ, et al. Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma. World J Gastroenterol 2009; 15:3493 - 7; http://dx.doi.org/10.3748/wjg.15.3493; PMID: 19630103
  • Ferguson HR, Wild CP, Anderson LA, Murphy SJ, Johnston BT, Murray LJ, et al. Cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphisms and risk of reflux esophagitis, Barrett esophagus, and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2008; 17:727 - 31; http://dx.doi.org/10.1158/1055-9965.EPI-07-2570; PMID: 18349295
  • Buttar NS, Wang KK, Anderson MA, Dierkhising RA, Pacifico RJ, Krishnadath KK, et al. The effect of selective cyclooxygenase-2 inhibition in Barrett esophagus epithelium: an in vitro study. J Natl Cancer Inst 2002; 94:422 - 9; http://dx.doi.org/10.1093/jnci/94.6.422; PMID: 11904314
  • Kaur BS, Khamnehei N, Iravani M, Namburu SS, Lin O, Triadafilopoulos G. Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett esophagus. Gastroenterology 2002; 123:60 - 7; http://dx.doi.org/10.1053/gast.2002.34244; PMID: 12105834
  • Cheong E, Ivory K, Doleman J, Parker ML, Rhodes M, Johnson IT. Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest. Carcinogenesis 2004; 25:1945 - 52; http://dx.doi.org/10.1093/carcin/bgh184; PMID: 15155531
  • Souza RF, Shewmake K, Beer DG, Cryer B, Spechler SJ. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res 2000; 60:5767 - 72; PMID: 11059772
  • Piazuelo E, Jiminez P, Strunk M, Santander S, Garcia A, Esteva F, et al. Effects of selective PGE2 receptor antagonists in esophageal adenocarcinoma cells derived from Barrett's esophagus. Prostaglandins &amp. Other Lipid Mediators 2006; 81:150 - 61; http://dx.doi.org/10.1016/j.prostaglandins.2006.09.002
  • Santander S, Cebrián C, Esquivias P, Conde B, Esteva F, Jiménez P, et al. Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice. Int J Oncol 2012; 40:527 - 34; PMID: 21971589
  • Heath EI, Canto MI, Piantadosi S, Montgomery E, Weinstein WM, Herman JG, et al, Chemoprevention for Barrett Esophagus Trial Research Group. Secondary chemoprevention of Barrett esophagus with celecoxib: results of a randomized trial. J Natl Cancer Inst 2007; 99:545 - 57; http://dx.doi.org/10.1093/jnci/djk112; PMID: 17405999
  • Jankowski J, Barr H, deCaestecker J, Watson P, Attwood S, Moayyedi P. Aspirin in the prevention of cancer. Lancet 2011; 377:1649 - 50, author reply 1651-2; http://dx.doi.org/10.1016/S0140-6736(11)60666-1; PMID: 21571137
  • Doak SH, Jenkins GJ, Parry EM, D’Souza FR, Griffiths AP, Toffazal N, et al. Chromosome 4 hyperploidy represents an early genetic aberration in premalignant Barrett oesophagus. Gut 2003; 52:623 - 8; http://dx.doi.org/10.1136/gut.52.5.623; PMID: 12692043
  • Abdel-Latif MM, O’Riordan J, Windle HJ, Carton E, Ravi N, Kelleher D, et al. NF-kappaB activation in esophageal adenocarcinoma: relationship to Barrett metaplasia, survival, and response to neoadjuvant chemoradiotherapy. Ann Surg 2004; 239:491 - 500; http://dx.doi.org/10.1097/01.sla.0000118751.95179.c6; PMID: 15024310
  • O’Riordan JM, Abdel-latif MM, Ravi N, McNamara D, Byrne PJ, McDonald GS, et al. Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol 2005; 100:1257 - 64; http://dx.doi.org/10.1111/j.1572-0241.2005.41338.x; PMID: 15929754
  • Jenkins GJ, Harries K, Doak SH, Wilmes A, Griffiths AP, Baxter JN, et al. The bile acid deoxycholic acid (DCA) at neutral pH activates NF-kappaB and induces IL-8 expression in oesophageal cells in vitro. Carcinogenesis 2004; 25:317 - 23; http://dx.doi.org/10.1093/carcin/bgh032; PMID: 14656946
  • Jenkins GJS, Cronin J, Alhamdani A, Rawat N, D’Souza F, Thomas T, et al. The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS. Mutagenesis 2008; 23:399 - 405; http://dx.doi.org/10.1093/mutage/gen029; PMID: 18515815
  • Huo X, Juergens S, Zhang X, Rezaei D, Yu C, Strauch ED, et al. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett epithelial cells. Am J Physiol Gastrointest Liver Physiol 2011; 301:G278 - 86; http://dx.doi.org/10.1152/ajpgi.00092.2011; PMID: 21636532
  • Hormi-Carver K, Zhang X, Zhang HY, Whitehead RH, Terada LS, Spechler SJ, et al. Unlike esophageal squamous cells, Barrett epithelial cells resist apoptosis by activating the nuclear factor-kappaB pathway. Cancer Res 2009; 69:672 - 7; http://dx.doi.org/10.1158/0008-5472.CAN-08-3703; PMID: 19147583
  • Awan AK, Iftikhar SY, Morris TM, Clarke PA, Grabowska AM, Waraich N, et al. Androgen receptors may act in a paracrine manner to regulate oesophageal adenocarcinoma growth. Eur J Surg Oncol 2007; 33:561 - 8; http://dx.doi.org/10.1016/j.ejso.2006.12.001; PMID: 17254742
  • Konturek PC, Nikiforuk A, Kania J, Raithel M, Hahn EG, Mühldorfer S. Activation of NFkappaB represents the central event in the neoplastic progression associated with Barrett esophagus: a possible link to the inflammation and overexpression of COX-2, PPARgamma and growth factors. Dig Dis Sci 2004; 49:1075 - 83; http://dx.doi.org/10.1023/B:DDAS.0000037790.11724.70; PMID: 15387324
  • Arber N, Gammon MD, Hibshoosh H, Britton JA, Zhang Y, Schonberg JB, et al. Overexpression of cyclin D1 occurs in both squamous carcinomas and adenocarcinomas of the esophagus and in adenocarcinomas of the stomach. Hum Pathol 1999; 30:1087 - 92; http://dx.doi.org/10.1016/S0046-8177(99)90227-7; PMID: 10492044
  • Arber N, Lightdale C, Rotterdam H, Han KH, Sgambato A, Yap E, et al. Increased expression of the cyclin D1 gene in Barrett esophagus. Cancer Epidemiol Biomarkers Prev 1996; 5:457 - 9; PMID: 8781742
  • Bani-Hani K, Martin IG, Hardie LJ, Mapstone N, Briggs JA, Forman D, et al. Prospective study of cyclin D1 overexpression in Barrett esophagus: association with increased risk of adenocarcinoma. J Natl Cancer Inst 2000; 92:1316 - 21; http://dx.doi.org/10.1093/jnci/92.16.1316; PMID: 10944553
  • Casson AG, Zheng Z, Evans SC, Geldenhuys L, van Zanten SV, Veugelers PJ, et al. Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma. Cancer 2005; 104:730 - 9; http://dx.doi.org/10.1002/cncr.21229; PMID: 15971196
  • Izzo JG, Wu T-T, Wu X, Ensor J, Luthra R, Pan J, et al. Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma. J Clin Oncol 2007; 25:698 - 707; http://dx.doi.org/10.1200/JCO.2006.08.0283; PMID: 17308274
  • Izzo JG, Malhotra U, Wu TT, Ensor J, Babenko IM, Swisher SG, et al. Impact of cyclin D1 A870G polymorphism in esophageal adenocarcinoma tumorigenesis. Semin Oncol 2005; 32:Suppl 9 S11 - 5; http://dx.doi.org/10.1053/j.seminoncol.2005.04.023; PMID: 16399423
  • Liu G, Cescon DW, Zhai R, Zhou W, Kulke MH, Ma C, et al. p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma. Dis Esophagus 2010; 23:36 - 9; http://dx.doi.org/10.1111/j.1442-2050.2009.00960.x; PMID: 19302219
  • Geddert H, Kiel S, Zotz RB, Zhang J, Willers R, Gabbert HE, et al. Polymorphism of p16 INK4A and cyclin D1 in adenocarcinomas of the upper gastrointestinal tract. J Cancer Res Clin Oncol 2005; 131:803 - 8; http://dx.doi.org/10.1007/s00432-005-0021-4; PMID: 16163549
  • Sarbia M, Bektas N, Müller W, Heep H, Borchard F, Gabbert HE. Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus. Cancer 1999; 86:2597 - 601; http://dx.doi.org/10.1002/(SICI)1097-0142(19991215)86:12<2597::AID-CNCR3>3.0.CO;2-0; PMID: 10594854
  • Lin L, Prescott MS, Zhu Z, Singh P, Chun SY, Kuick RD, et al. Identification and characterization of a 19q12 amplicon in esophageal adenocarcinomas reveals cyclin E as the best candidate gene for this amplicon. Cancer Res 2000; 60:7021 - 7; PMID: 11156406
  • Boynton RF, Huang Y, Blount PL, Reid BJ, Raskind WH, Haggitt RC, et al. Frequent loss of heterozygosity at the retinoblastoma locus in human esophageal cancers. Cancer Res 1991; 51:5766 - 9; PMID: 1913694
  • Morgan RJ, Newcomb PV, Bailey M, Hardwick RH, Alderson D. Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma. [EJSO] Eur J Surg Oncol 1998; 24:34 - 7; http://dx.doi.org/10.1016/S0748-7983(98)80122-4; PMID: 9542513
  • Huang Y, Meltzer SJ, Yin J, Tong Y, Chang EH, Srivastava S, et al. Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas. Cancer Res 1993; 53:1889 - 94; PMID: 8467510
  • Sarbia M, Arjumand J, Wolter M, Reifenberger G, Heep H, Gabbert HE. Frequent c-myc amplification in high-grade dysplasia and adenocarcinoma in Barrett esophagus. Am J Clin Pathol 2001; 115:835 - 40; http://dx.doi.org/10.1309/MXXH-25N3-UAL2-G7XX; PMID: 11392879
  • Klump B, Hsieh CJ, Holzmann K, Gregor M, Porschen R. Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett esophagus. Gastroenterology 1998; 115:1381 - 6; http://dx.doi.org/10.1016/S0016-5085(98)70016-2; PMID: 9834265
  • Wong DJ, Paulson TG, Prevo LJ, Galipeau PC, Longton G, Blount PL, et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett metaplastic epithelium. Cancer Res 2001; 61:8284 - 9; PMID: 11719461
  • Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Reid BJ. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett esophagus. Cancer Res 2004; 64:3414 - 27; http://dx.doi.org/10.1158/0008-5472.CAN-03-3249; PMID: 15150093
  • Schulmann K, Sterian A, Berki A, Yin J, Sato F, Xu Y, et al. Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett-associated neoplastic progression and predicts progression risk. Oncogene 2005; 24:4138 - 48; http://dx.doi.org/10.1038/sj.onc.1208598; PMID: 15824739
  • Singh SP, Lipman J, Goldman H, Ellis FH Jr., Aizenman L, Cangi MG, et al. Loss or altered subcellular localization of p27 in Barrett associated adenocarcinoma. Cancer Res 1998; 58:1730 - 5; PMID: 9563491
  • Ellis FH Jr., Xu X, Kulke MH, LoCicero J 3rd, Loda M. Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice. J Thorac Cardiovasc Surg 2001; 122:809 - 14; http://dx.doi.org/10.1067/mtc.2001.116471; PMID: 11581618
  • Hanas JS, Lerner MR, Lightfoot SA, Raczkowski C, Kastens DJ, Brackett DJ, et al. Expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumor suppressor in dysplastic progression and adenocarcinoma in Barrett esophagus. Cancer 1999; 86:756 - 63; http://dx.doi.org/10.1002/(SICI)1097-0142(19990901)86:5<756::AID-CNCR9>3.0.CO;2-X; PMID: 10463972
  • Huang Y, Boynton RF, Blount PL, Silverstein RJ, Yin J, Tong Y, et al. Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. Cancer Res 1992; 52:6525 - 30; PMID: 1423299
  • Hamelin R, Fléjou JF, Muzeau F, Potet F, Laurent-Puig P, Fékété F, et al. TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett esophagus. Gastroenterology 1994; 107:1012 - 8; PMID: 7523212
  • Schneider PM, Casson AG, Levin B, Garewal HS, Hoelscher AH, Becker K, et al. Mutations of p53 in Barrett esophagus and Barrett cancer: a prospective study of ninety-eight cases. J Thorac Cardiovasc Surg 1996; 111:323 - 31, discussion 331-3; http://dx.doi.org/10.1016/S0022-5223(96)70441-5; PMID: 8583805
  • Blount PL, Galipeau PC, Sanchez CA, Neshat K, Levine DS, Yin J, et al. 17p allelic losses in diploid cells of patients with Barrett esophagus who develop aneuploidy. Cancer Res 1994; 54:2292 - 5; PMID: 8162566
  • Ribeiro U Jr., Finkelstein SD, Safatle-Ribeiro AV, Landreneau RJ, Clarke MR, Bakker A, et al. p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma. Cancer 1998; 83:7 - 18; http://dx.doi.org/10.1002/(SICI)1097-0142(19980701)83:1<7::AID-CNCR2>3.0.CO;2-R; PMID: 9655287
  • Schneider PM, Stoeltzing O, Roth JA, Hoelscher AH, Wegerer S, Mizumoto S, et al. P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett esophagus. Clin Cancer Res 2000; 6:3153 - 8; PMID: 10955797
  • Casson AG, Evans SC, Gillis A, Porter GA, Veugelers P, Darnton SJ, et al. Clinical implications of p53 tumor suppressor gene mutation and protein expression in esophageal adenocarcinomas: results of a ten-year prospective study. J Thorac Cardiovasc Surg 2003; 125:1121 - 31; http://dx.doi.org/10.1067/mtc.2003.176; PMID: 12771886
  • Ireland AP, Shibata DK, Chandrasoma P, Lord RV, Peters JH, DeMeester TR. Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia. Ann Surg 2000; 231:179 - 87; http://dx.doi.org/10.1097/00000658-200002000-00005; PMID: 10674608
  • Blount PL, Ramel S, Raskind WH, Haggitt RC, Sanchez CA, Dean PJ, et al. 17p allelic deletions and p53 protein overexpression in Barrett adenocarcinoma. Cancer Res 1991; 51:5482 - 6; PMID: 1680552
  • Ramel S, Reid BJ, Sanchez CA, Blount PL, Levine DS, Neshat K, et al. Evaluation of p53 protein expression in Barrett esophagus by two-parameter flow cytometry. Gastroenterology 1992; 102:1220 - 8; PMID: 1551529
  • Younes M, Lebovitz RM, Lechago LV, Lechago J. p53 protein accumulation in Barrett metaplasia, dysplasia, and carcinoma: a follow-up study. Gastroenterology 1993; 105:1637 - 42; PMID: 8253340
  • Rice TW, Goldblum JR, Falk GW, Tubbs RR, Kirby TJ, Casey G. p53 immunoreactivity in Barrett metaplasia, dysplasia, and carcinoma. J Thorac Cardiovasc Surg 1994; 108:1132 - 7; PMID: 7983883
  • Doak SH, Jenkins GJ, Parry EM, Griffiths AP, Shah V, Baxter JN, et al. Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma. Br J Cancer 2003; 89:1729 - 35; http://dx.doi.org/10.1038/sj.bjc.6601323; PMID: 14583777
  • Hanazono K, Natsugoe S, Stein HJ, Aikou T, Hoefler H, Siewert JR. Distribution of p53 mutations in esophageal and gastric carcinomas and the relationship with p53 expression. Oncol Rep 2006; 15:821 - 4; PMID: 16525665
  • Hritz I, Gyorffy H, Molnar B, Lakatos G, Sipos F, Pregun I, et al. Increased p53 expression in the malignant transformation of Barrett esophagus is accompanied by an upward shift of the proliferative compartment. Pathol Oncol Res 2009; 15:183 - 92; http://dx.doi.org/10.1007/s12253-008-9095-z; PMID: 18752044
  • Binato M, Gurski RR, Fagundes RB, Meurer L, Edelweiss MI. P53 and Ki-67 overexpression in gastroesophageal reflux disease--Barrett esophagus and adenocarcinoma sequence. Dis Esophagus 2009; 22:588 - 95; http://dx.doi.org/10.1111/j.1442-2050.2009.00953.x; PMID: 19302208
  • Kastelein F, Biermann K, Steyerberg EW, Verheij J, Kalisvaart M, Looijenga LH, et al, on behalf of the ProBar-study group. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett oesophagus. Gut 2012; http://dx.doi.org/10.1136/gutjnl-2012-303594; PMID: 23256952
  • Osterheld MC, Bian YS, Bosman FT, Benhattar J, Fontolliet C. Beta-catenin expression and its association with prognostic factors in adenocarcinoma developed in Barrett esophagus. Am J Clin Pathol 2002; 117:451 - 6; http://dx.doi.org/10.1309/1DB6-GFVH-RA6W-Q07Y; PMID: 11888085
  • Wijnhoven BP, Nollet F, De Both NJ, Tilanus HW, Dinjens WN. Genetic alterations involving exon 3 of the beta-catenin gene do not play a role in adenocarcinomas of the esophagus. Int J Cancer 2000; 86:533 - 7; http://dx.doi.org/10.1002/(SICI)1097-0215(20000515)86:4<533::AID-IJC15>3.0.CO;2-O; PMID: 10797268
  • Bian YS, Osterheld MC, Bosman FT, Fontolliet C, Benhattar J. Nuclear accumulation of beta-catenin is a common and early event during neoplastic progression of Barrett esophagus. Am J Clin Pathol 2000; 114:583 - 90; http://dx.doi.org/10.1309/3QLC-5MF1-JYXU-A5XX; PMID: 11026105
  • Choi YW, Heath EI, Heitmiller R, Forastiere AA, Wu T-T. Mutations in beta-catenin and APC genes are uncommon in esophageal and esophagogastric junction adenocarcinomas. Mod Pathol 2000; 13:1055 - 9; http://dx.doi.org/10.1038/modpathol.3880194; PMID: 11048797
  • González MV, Artímez ML, Rodrigo L, López-Larrea C, Menéndez MJ, Alvarez V, et al. Mutation analysis of the p53, APC, and p16 genes in the Barrett oesophagus, dysplasia, and adenocarcinoma. J Clin Pathol 1997; 50:212 - 7; http://dx.doi.org/10.1136/jcp.50.3.212; PMID: 9155671
  • Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst 2000; 92:1805 - 11; http://dx.doi.org/10.1093/jnci/92.22.1805; PMID: 11078757
  • Eads CA, Lord RV, Wickramasinghe K, Long TI, Kurumboor SK, Bernstein L, et al. Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Res 2001; 61:3410 - 8; PMID: 11309301
  • Clément G, Braunschweig R, Pasquier N, Bosman FT, Benhattar J. Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett oesophagus patients at risk for malignant transformation. J Pathol 2006; 208:100 - 7; http://dx.doi.org/10.1002/path.1884; PMID: 16278815
  • Clément G, Braunschweig R, Pasquier N, Bosman FT, Benhattar J. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett esophagus. Oncogene 2006; 25:3084 - 92; http://dx.doi.org/10.1038/sj.onc.1209338; PMID: 16407829
  • Clément G, Guilleret I, He B, Yagui-Beltrán A, Lin Y-C, You L, et al. Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett esophagus. Cancer Sci 2008; 99:46 - 53; PMID: 18005197
  • Bailey T, Biddlestone L, Shepherd N, Barr H, Warner P, Jankowski J. Altered cadherin and catenin complexes in the Barrett esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation. Am J Pathol 1998; 152:135 - 44; PMID: 9422531
  • Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Kremers ED, Dinjens WN, et al. Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol 1997; 182:331 - 8; http://dx.doi.org/10.1002/(SICI)1096-9896(199707)182:3<331::AID-PATH860>3.0.CO;2-D; PMID: 9349237
  • Corn PG, Heath EI, Heitmiller R, Fogt F, Forastiere AA, Herman JG, et al. Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res 2001; 7:2765 - 9; PMID: 11555590
  • Tselepis C, Perry I, Dawson C, Hardy R, Darnton SJ, McConkey C, et al. Tumour necrosis factor-alpha in Barrett oesophagus: a potential novel mechanism of action. Oncogene 2002; 21:6071 - 81; http://dx.doi.org/10.1038/sj.onc.1205731; PMID: 12203119
  • Jethwa P, Naqvi M, Hardy RG, Hotchin NA, Roberts S, Spychal R, et al. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma. World J Gastroenterol 2008; 14:1044 - 52; http://dx.doi.org/10.3748/wjg.14.1044; PMID: 18286686
  • van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 2005; 435:959 - 63; http://dx.doi.org/10.1038/nature03659; PMID: 15959515
  • Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 2001; 294:2155 - 8; http://dx.doi.org/10.1126/science.1065718; PMID: 11739954
  • Menke V, van Es JH, de Lau W, van den Born M, Kuipers EJ, Siersema PD, et al. Conversion of metaplastic Barrett epithelium into post-mitotic goblet cells by gamma-secretase inhibition. Dis Model Mech 2010; 3:104 - 10; http://dx.doi.org/10.1242/dmm.003012; PMID: 20075383
  • Tamagawa Y, Ishimura N, Uno G, Yuki T, Kazumori H, Ishihara S, et al. Notch signaling pathway and Cdx2 expression in the development of Barrett esophagus. Lab Invest 2012; 92:896 - 909; http://dx.doi.org/10.1038/labinvest.2012.56; PMID: 22449796
  • Morrow DJ, Avissar NE, Toia L, Redmond EM, Watson TJ, Jones C, et al. Pathogenesis of Barrett esophagus: bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells. Surgery 2009; 146:714 - 21, discussion 721-2; http://dx.doi.org/10.1016/j.surg.2009.06.050; PMID: 19789031
  • Mendelson J, Song S, Li Y, Maru DM, Mishra B, Davila M, et al. Dysfunctional transforming growth factor-β signaling with constitutively active Notch signaling in Barrett esophageal adenocarcinoma. Cancer 2011; 117:3691 - 702; http://dx.doi.org/10.1002/cncr.25861; PMID: 21305538
  • Song S, Maru DM, Ajani JA, Chan CH, Honjo S, Lin HK, et al. Loss of TGF-β adaptor β2SP activates notch signaling and SOX9 expression in esophageal adenocarcinoma. Cancer Res 2013; 73:2159 - 69; http://dx.doi.org/10.1158/0008-5472.CAN-12-1962; PMID: 23536563
  • van den Brink GR. Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiol Rev 2007; 87:1343 - 75; http://dx.doi.org/10.1152/physrev.00054.2006; PMID: 17928586
  • Litingtung Y, Lei L, Westphal H, Chiang C. Sonic hedgehog is essential to foregut development. Nat Genet 1998; 20:58 - 61; http://dx.doi.org/10.1038/1717; PMID: 9731532
  • Wang DH, Clemons NJ, Miyashita T, Dupuy AJ, Zhang W, Szczepny A, et al. Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett metaplasia. Gastroenterology 2010; 138:1810 - 22; http://dx.doi.org/10.1053/j.gastro.2010.01.048; PMID: 20138038
  • Yamanaka Y, Shiotani A, Fujimura Y, Ishii M, Fujita M, Matsumoto H, et al. Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus. Dig Liver Dis 2011; 43:54 - 9; http://dx.doi.org/10.1016/j.dld.2010.04.014; PMID: 20619754
  • Castillo D, Puig S, Iglesias M, Seoane A, de Bolós C, Munitiz V, et al. Activation of the BMP4 pathway and early expression of CDX2 characterize non-specialized columnar metaplasia in a human model of Barrett esophagus. J Gastrointest Surg 2012; 16:227 - 37, discussion 237; http://dx.doi.org/10.1007/s11605-011-1758-5; PMID: 22076569
  • Milano F, van Baal JW, Buttar NS, Rygiel AM, de Kort F, DeMars CJ, et al. Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells. Gastroenterology 2007; 132:2412 - 21; http://dx.doi.org/10.1053/j.gastro.2007.03.026; PMID: 17570215
  • Clemons NJ, Wang DH, Croagh D, Tikoo A, Fennell CM, Murone C, et al. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett esophagus. Am J Physiol Gastrointest Liver Physiol 2012; 303:G1335 - 46; http://dx.doi.org/10.1152/ajpgi.00291.2012; PMID: 23064761
  • Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425:846 - 51; http://dx.doi.org/10.1038/nature01972; PMID: 14520411
  • Rizvi S, Demars CJ, Comba A, Gainullin VG, Rizvi Z, Almada LL, et al. Combinatorial chemoprevention reveals a novel smoothened-independent role of GLI1 in esophageal carcinogenesis. Cancer Res 2010; 70:6787 - 96; http://dx.doi.org/10.1158/0008-5472.CAN-10-0197; PMID: 20647328
  • Wang Y, Ding Q, Yen CJ, Xia W, Izzo JG, Lang JY, et al. The crosstalk of mTOR/S6K1 and Hedgehog pathways. Cancer Cell 2012; 21:374 - 87; http://dx.doi.org/10.1016/j.ccr.2011.12.028; PMID: 22439934
  • Yen CJ, Izzo JG, Lee DF, Guha S, Wei Y, Wu TT, et al. Bile acid exposure up-regulates tuberous sclerosis complex 1/mammalian target of rapamycin pathway in Barrett-associated esophageal adenocarcinoma. Cancer Res 2008; 68:2632 - 40; http://dx.doi.org/10.1158/0008-5472.CAN-07-5460; PMID: 18413730
  • Schmidt MK, Meurer L, Volkweis BS, Edelweiss MI, Schirmer CC, Kruel CDP, et al. c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Dis Esophagus 2007; 20:212 - 6; http://dx.doi.org/10.1111/j.1442-2050.2007.00673.x; PMID: 17509117
  • Tselepis C, Morris CD, Wakelin D, Hardy R, Perry I, Luong QT, et al. Upregulation of the oncogene c-myc in Barrett adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut 2003; 52:174 - 80; http://dx.doi.org/10.1136/gut.52.2.174; PMID: 12524396
  • von Rahden BH, Stein HJ, Pühringer-Oppermann F, Sarbia M. c-myc amplification is frequent in esophageal adenocarcinoma and correlated with the upregulation of VEGF-A expression. Neoplasia 2006; 8:702 - 7; http://dx.doi.org/10.1593/neo.06277; PMID: 16984727
  • Nancarrow DJ, Handoko HY, Smithers BM, Gotley DC, Drew PA, Watson DI, et al. Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays. Cancer Res 2008; 68:4163 - 72; http://dx.doi.org/10.1158/0008-5472.CAN-07-6710; PMID: 18519675
  • Stairs DB, Nakagawa H, Klein-Szanto A, Mitchell SD, Silberg DG, Tobias JW, et al. Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett esophagus. PLoS One 2008; 3:e3534; http://dx.doi.org/10.1371/journal.pone.0003534; PMID: 18953412
  • Hoyo C, Cook MB, Kamangar F, Freedman ND, Whiteman DC, Bernstein L, et al. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium. Int J Epidemiol 2012; 41:1706 - 18; http://dx.doi.org/10.1093/ije/dys176; PMID: 23148106
  • Kubo A, Cook MB, Shaheen NJ, Vaughan TL, Whiteman DC, Murray L, et al. Sex-specific associations between body mass index, waist circumference and the risk of Barrett oesophagus: a pooled analysis from the international BEACON consortium. Gut 2013; http://dx.doi.org/10.1136/gutjnl-2012-303753; PMID: 23355549
  • Su Z, Gay LJ, Strange A, Palles C, Band G, Whiteman DC, et al, Esophageal Adenocarcinoma Genetics Consortium, Wellcome Trust Case Control Consortium 2. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett esophagus. Nat Genet 2012; 44:1131 - 6; http://dx.doi.org/10.1038/ng.2408; PMID: 22961001