Skip to main content
SpringerLink
Log in

Cyclooxygenase activity in gastrointestinal cancer development and progression: prospects as a therapeutic target

  • Chapter
Book cover Cancer and Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Gastrointestinal malignancies are a leading cause of morbidity and mortality worldwide. The Global Burden of Disease study estimated that in 1990 cancers of the gastrointestinal tract were responsible for more than 40% of all cancer deaths, nearly 2.2 million people [1, 2]. Interestingly, the incidence of these cancers can vary considerably between regions. This is most likely due to a variety of factors including environmental exposures, diet, social habits, and genetic backgrounds. Given the enormity of the problem, it has been the focus of intense research for many years. A great deal has been learned about the mechanisms governing the development and progression of human cancers. Research over the last decade has established that the progression from normal tissue to neoplasia is in every case a stepwise process [3-5]. Genetic and epigenetic instability appears fundamentally important to this process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Parkin DM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49 (1): 33–64

    PubMed  CAS  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94 (2): 153–156

    PubMed  CAS  Google Scholar 

  3. Lynch JP, Hoops TC (2002) The genetic pathogenesis of colorectal cancer. Hematol Oncology Clinics of North America 16 (4): 1–36

    Google Scholar 

  4. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61 (5): 759–767

    PubMed  CAS  Google Scholar 

  5. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87 (2): 159–170

    PubMed  CAS  Google Scholar 

  6. Sepulveda AR, Graham DY (2002) Role of Helicobacter pylori in gastric carcinogenesis. Gastroenterol Clin North Am 31 (2): 517–535

    PubMed  Google Scholar 

  7. Hu KQ (2002) Rationale and feasibility of chemoprevention of hepatocellular carcinoma by cyclooxygenase-2 inhibitors. J Lab Clin Med 139 (4): 234–243

    PubMed  CAS  Google Scholar 

  8. el-Serag HB (2002) The epidemic of esophageal adenocarcinoma. Gastroenterol Clin North Am 31 (2): 421–440

    PubMed  Google Scholar 

  9. Koga H (2003) Hepatocellular carcinoma: is there a potential for chemoprevention using cyclooxygenase-2 inhibitors? Cancer 98 (4): 661–667

    PubMed  CAS  Google Scholar 

  10. Farrow B, Evers BM (2002) Inflammation and the development of pancreatic cancer. Surg Oncol 10 (4): 153–169

    PubMed  Google Scholar 

  11. Whitcomb DC, Pogue-Geile K (2002) Pancreatitis as a risk for pancreatic cancer. Gastroenterol Clin North Am 31 (2): 663–678

    PubMed  Google Scholar 

  12. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T et al (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342 (26): 1946–1952

    PubMed  CAS  Google Scholar 

  13. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L et al (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50 (6): 857–860

    PubMed  CAS  Google Scholar 

  14. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328 (18): 1313–1316

    PubMed  CAS  Google Scholar 

  15. Cruz-Correa M, Hylind LM, Romans KE, Booker SV, Giardiello FM (2002) Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study. Gastroenterology 122 (3): 641–645

    PubMed  CAS  Google Scholar 

  16. Milas L, Mason KA, Crane CH, Liao Z, Masferrer J (2003) Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme. Oncology (Huntingt) 17 (5 Suppl 5): 15–24

    Google Scholar 

  17. Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94 (4): 252–266

    PubMed  CAS  Google Scholar 

  18. Choy H, Milas L (2003) Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst 95 (19): 1440–1452

    PubMed  CAS  Google Scholar 

  19. Ohshima H, Tatemichi M, Sawa T (2003) Chemical basis of inflammation-induced carcinogenesis. Arch Biochem Biophys 417 (1): 3–11

    PubMed  CAS  Google Scholar 

  20. Marks F, Furstenberger G (2000) Cancer chemoprevention through interruption of multistage carcinogenesis. The lessons learnt by comparing mouse skin carcinogenesis and human large bowel cancer. Eur J Cancer 36 (3): 314–329

    PubMed  CAS  Google Scholar 

  21. Mocellin S, Wang E, Marincola FM (2001) Cytokines and immune response in the tumor microenvironment. J Immunother 24 (5): 392–407

    CAS  Google Scholar 

  22. Saito S, Kitayama J, Jin ZX, Tsuno N, Kaisaki S, Seto Y, Nagawa H (2003) Betachemokine, macrophage inflammatory protein-1beta (MIP-lbeta), is highly expressed in diffuse type human gastric cancers. J Exp Clin Cancer Res 22 (3): 453–459

    PubMed  CAS  Google Scholar 

  23. Salcedo R, Oppenheim JJ (2003) Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Micro circulation 10 (3–4): 359–370

    CAS  Google Scholar 

  24. White ES, Strieter RM, Arenberg DA (2002) Chemokines as therapeutic targets in non-small cell lung cancer. Curr Med Chem Anti-Cant Agents 2 (3): 403–417

    CAS  Google Scholar 

  25. Balkwill F (2002) Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev 13 (2): 135–141

    PubMed  CAS  Google Scholar 

  26. Krishnan K, Brenner DE (2001) Prostaglandin inhibitors and the chemoprevention of noncolonic malignancy. Gastroenterol Clin North Am 30 (4): 981–1000

    PubMed  CAS  Google Scholar 

  27. Crofford LJ (2001) Prostaglandin biology. Gastroenterol Clin North Am 30 (4): 863–876

    PubMed  CAS  Google Scholar 

  28. Goodlad RA, Lee CY, Levin S, Wright NA (1991) Effects of the prostaglandin analogue misoprostol on cell proliferation in the canine small intestine. Exp Physiol 76 (4): 561–566

    PubMed  CAS  Google Scholar 

  29. Goodlad RA, Madgwick AJ, Moffatt MR, Levin S, Allen JL, Wright NA (1990) The effects of the prostaglandin analogue, misoprostol, on cell proliferation and cell migration in the canine stomach. Digestion 46 (Suppl 2): 182–187

    PubMed  CAS  Google Scholar 

  30. Rudnick DA, Perlmutter DH, Muglia LJ (2001) Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration. Proc Natl Acad Sci USA 98 (15): 8885–8890

    PubMed  CAS  Google Scholar 

  31. Dormond O, Foletti A, Paroz C, Ruegg C (2001) NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis. Nat Med 7 (9): 1041–1047

    PubMed  CAS  Google Scholar 

  32. Fosslien E (2001) Review: molecular pathology of cyclooxygenase-2 in cancer-induced angiogenesis. Ann Clin Lab Sci 31 (4): 325–348

    PubMed  CAS  Google Scholar 

  33. Roper RL, Phipps RP (1994) Prostaglandin E2 regulation of the immune response. Adv Prostaglandin Thromboxane Leukot Res 22: 101–111

    PubMed  CAS  Google Scholar 

  34. Kucharzik T, Lugering N, Winde G, Domschke W, Stoll R (1997) Colon carcinoma cell lines stimulate monocytes and lamina propria mononuclear cells to produce IL-10. Clin Exp Immunol 110 (2): 296–302

    PubMed  CAS  Google Scholar 

  35. Kambayashi T, Alexander HR, Fong M, Strassmann G (1995) Potential involvement of IL-10 in suppressing tumor-associated macrophages. Colon-26-derived prostaglandin E2 inhibits TNF-alpha release via a mechanism involving IL-10. J Immunol 154 (7): 3383–3390

    PubMed  CAS  Google Scholar 

  36. Wang Z, Chen Y, Zheng R, Qin D, Chen X, Wang Y, Liu G (1997) in vitro effects of prostaglandin E2 or indomethacin on the proliferation of lymphokine-activated killer cells and their cytotoxicity against bladder tumor cells in patients with bladder cancer. Prostaglandins 54 (5): 769–779

    PubMed  CAS  Google Scholar 

  37. Hilkens CM, Snijders A, Snijdewint FG, Wierenga EA, Kapsenberg ML (1996) Modulation of T-cell cytokine secretion by accessory cell-derived products. Eur Respir J Suppl 22: 90s-94s

    PubMed  CAS  Google Scholar 

  38. Marcinkiewicz J (1997) Regulation of cytokine production by eicosanoids and nitric oxide. Arch Immunol Ther Exp (Warsz) 45 (2–3): 163–167

    CAS  Google Scholar 

  39. Shao J, Lee SB, Guo H, Evers BM, Sheng H (2003) Prostaglandin E2 stimulates the growth of colon cancer cells via induction of amphiregulin. Cancer Res 63 (17): 5218–5223

    PubMed  CAS  Google Scholar 

  40. Okuno M, Kojima S, Moriwaki H (2001) Chemoprevention of hepatocellular carcinoma: concept, progress and perspectives. J Gastroenterol Hepatol 16 (12): 1329–1335

    PubMed  CAS  Google Scholar 

  41. Ahmad A, Govil Y, Frank BB (2003) Gastric mucosa-associated lymphoid tissue lymphoma. Am J Gastroenterol 98 (5): 975–986

    PubMed  Google Scholar 

  42. Allgayer H (2003) Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther 18 (Suppl 2): 10–14

    PubMed  CAS  Google Scholar 

  43. Itzkowitz SH (2002) Cancer prevention in patients with inflammatory bowel disease. Gastroenterol Clin North Am 31 (4): 1133–1144

    PubMed  Google Scholar 

  44. Robinson DR (1997) Regulation of prostaglandin synthesis by antiinflammatory drugs. J Rheumatol (Suppl) 47: 32–39

    CAS  Google Scholar 

  45. Tazawa R, Xu XM, Wu KK, Wang LH (1994) Characterization of the genomic structure, chromosomal location and promoter of human prostaglandin H synthase-2 gene. Biochem Biophys Res Commun 203 (1): 190–199

    PubMed  CAS  Google Scholar 

  46. Kraemer SA, Arthur KA, Denison MS, Smith WL, DeWitt DL (1996) Regulation of prostaglandin endoperoxide H synthase-2 expression by 2,3,7,8,-tetrachlorodibenzo-pdioxin. Arch Biochem Biophys 330 (2): 319–328

    PubMed  CAS  Google Scholar 

  47. Sirois J, Levy LO, Simmons DL, Richards JS (1993) Characterization and hormonal regulation of the promoter of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Identification of functional and protein-binding regions. J Biol Chem 268 (16): 12199–12206

    PubMed  CAS  Google Scholar 

  48. Liu J, Antaya M, Boerboom D, Lussier JG, Silversides DW, Sirois J (1999) The delayed activation of the prostaglandin G/H synthase-2 promoter in bovine granulosa cells is associated with down-regulation of truncated upstream stimulatory factor-2. J Biol Chem 274 (49): 35037–35045

    PubMed  CAS  Google Scholar 

  49. Trifan OC, Hla T (2003) Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis. J Cell Mol Med 7 (3): 207–222

    PubMed  CAS  Google Scholar 

  50. Sheng H, Shao J, Dubois RN (2001) K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res 61 (6): 2670–2675

    PubMed  CAS  Google Scholar 

  51. Blanco JC, Contursi C, Salkowski CA, DeWitt DL, Ozato K, Vogel SN (2000) Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression. J Exp Med 191(12): 2131–2144

    PubMed  CAS  Google Scholar 

  52. Guo YS, Cheng JZ, Jin GF, Gutkind JS, Hellmich MR, Townsend CM Jr (2002) Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERKS kinase and transactivation of the epidermal growth factor receptor. J Biol Chem 277 (50): 48755–48763

    PubMed  CAS  Google Scholar 

  53. Seo JH, Kim H, Kim KH (2002) Cyclooxygenase-2 expression by transcription factors in Helicobacter pylori-infected gastric epithelial cells: comparison between HP 99 and NCTC 11637. Ann NY Acad Sci 973: 477–480

    PubMed  CAS  Google Scholar 

  54. Tessner TG, Muhale F, Schloemann S, Cohn SM, Morrison A, Stenson WF (2003) Basic fibroblast growth factor upregulates cyclooxygenase-2 in 1407 cells through p38 MAP kinase. Am J Physiol Gastrointest Liver Physiol 284 (2): G269–G279

    PubMed  CAS  Google Scholar 

  55. Zhao H, Tian W, Tai C, Cohen DM (2003) Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR. Am J Physiol Renal Physiol 285 (2): F281–F288

    PubMed  CAS  Google Scholar 

  56. Faour WH, Mancini A, He QW, Di Battista JA (2003) T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade: role of distal sequences in the 3’-untranslated region of COX-2 mRNA. J Biol Chem 278 (29): 26897–26907

    PubMed  CAS  Google Scholar 

  57. Juttner S, Cramer T, Wessler S, Walduck A, Gao F, Schmitz F, Wunder C, Weber M, Fischer SM, Schmidt WE et al (2003) Helicobacter pylori stimulates host cyclooxygenase2 gene transcription: critical importance of MEK/ERK-dependent activation of USF1/-2 and CREB transcription factors. Cell Microbiol 5 (11): 821–834

    PubMed  Google Scholar 

  58. Huang WC, Chen JJ, Inoue H, Chen CC (2003) Tyrosine phosphorylation of I-kappa B kinase alpha/beta by protein kinase C-dependent c-Src activation is involved in TNFalpha-induced cyclooxygenase-2 expression. J Immunol 170 (9): 4767–4775

    PubMed  CAS  Google Scholar 

  59. Glinghammar B, Skogsberg J, Hamsten A, Ehrenborg E (2003) PPARdelta activation induces COX-2 gene expression and cell proliferation in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 308 (2): 361–368

    PubMed  CAS  Google Scholar 

  60. Han S, Inoue H, Flowers LC, Sidell N (2003) Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells. Clin Cancer Res 9 (12): 4627–4635

    PubMed  CAS  Google Scholar 

  61. Araki Y, Okamura S, Hussain SP, Nagashima M, He P, Shiseki M, Miura K, Harris CC (2003) Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res 63 (3): 728–734

    PubMed  CAS  Google Scholar 

  62. Newton R, Kuitert LM, Bergmann M, Adcock IM, Barnes PJ (1997) Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta. Biochem Biophys Res Commun 237 (1): 28–32

    PubMed  CAS  Google Scholar 

  63. Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298 (5600): 1911–1912

    PubMed  CAS  Google Scholar 

  64. Sheng H, Williams CS, Shao J, Liang P, DuBois RN, Beauchamp RD (1998) Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein kinase pathway. J Biol Chem 273 (34): 22120–22127

    PubMed  CAS  Google Scholar 

  65. Lara-Pezzi E, Gomez-Gaviro MV, Galvez BG, Mira E, Iniguez MA, Fresno M, Martinez AC, Arroyo AG, Lopez-Cabrera M (2002) The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. J Clin Invest 110(12): 1831–1838

    PubMed  CAS  Google Scholar 

  66. Sengupta S, Jang BC, Wu MT, Paik JH, Furneaux H, Hla T (2003) The RNA-binding protein HuR regulates the expression of cyclooxygenase-2. J Biol Chem 278 (27): 25227–25233

    PubMed  CAS  Google Scholar 

  67. Gou Q, Liu CH, Ben-Av P, Hla T (1998) Dissociation of basal turnover and cytokineinduced transcript stabilization of the human cyclooxygenase-2 mRNA by mutagenesis of the 3’-untranslated region. Biochem Biophys Res Commun 242 (3): 508–512

    PubMed  CAS  Google Scholar 

  68. Ristimaki A, Narko K, Hla T (1996) Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by dexamethasone: evidence for post-transcriptional regulation. Biochem J 318 (Pt 1): 325–331

    PubMed  CAS  Google Scholar 

  69. Monick MM, Robeff PK, Butler NS, Flaherty DM, Carter AB, Peterson MW, Hunninghake GW (2002) Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA. J Biol Chem 277 (36): 32992–33000

    PubMed  CAS  Google Scholar 

  70. Dixon DA, Kaplan CD, McIntyre TM, Zimmerman GA, Prescott SM (2000) Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3’-untranslated region. J Biol Chem 275 (16): 11750–11757

    PubMed  CAS  Google Scholar 

  71. Hawkey CJ, Jones JI (2001) Gastrointestinal safety of COX-2 specific inhibitors. Gastroenterol Clin North Am 30 (4): 921–936

    PubMed  CAS  Google Scholar 

  72. Cohn SM, Schloemann S, Tessner T, Seibert K, Stenson WF (1997) Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1. J Clin Invest 99 (6): 1367–1379

    PubMed  CAS  Google Scholar 

  73. Houchen CW, Stenson WF, Cohn SM (2000) Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury. Am J Physiol Gastrointest Liver Physiol 279 (5): G858–865

    PubMed  CAS  Google Scholar 

  74. Cryer B (2001) Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. Gastroenterol Clin North Am 30 (4): 877–894

    PubMed  CAS  Google Scholar 

  75. Kandil HM, Tanner G, Smalley W, Halter S, Radhika A, Dubois RN (2001) Cyclooxygenase-2 expression in Barrett’s esophagus. Dig Dis Sci 46 (4): 785–789

    PubMed  CAS  Google Scholar 

  76. Singer II, Kawka DW, Schloemann S, Tessner T, Riehl T, Stenson WF (1998) Cyclooxygenase 2 is induced in colonic epithelial cells in inflammatory bowel disease. Gastroenterology 115 (2): 297–306

    PubMed  CAS  Google Scholar 

  77. Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, Schror K (1999) Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 59 (1): 198–204

    PubMed  CAS  Google Scholar 

  78. Shamma A, Yamamoto H, Doki Y, Okami J, Kondo M, Fujiwara Y, Yano M, Inoue M, Matsuura N, Shiozaki H et al (2000) Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. Clin Cancer Res 6 (4): 1229–1238

    PubMed  CAS  Google Scholar 

  79. Yu HP, Xu SQ, Liu L, Shi LY, Cai XK, Lu WH, Lu B, Su YH, Li YY (2003) Cyclooxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus. Cancer Lett 198 (2): 193–201

    PubMed  CAS  Google Scholar 

  80. Aggarwal S, Taneja N, Lin L, Orringer MB, Rehemtulla A, Beer DG (2000) Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves upregulation of Bax and translocation of mitochondrial cytochrome C independent of COX-2 expression. Neoplasia 2 (4): 346–356

    PubMed  CAS  Google Scholar 

  81. Wilson KT, Fu S, Ramanujam KS, Meltzer SJ (1998) Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res 58 (14): 2929–2934

    PubMed  CAS  Google Scholar 

  82. Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G (2000) Cyclooxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology 118 (3): 487–496

    PubMed  CAS  Google Scholar 

  83. Morris CD, Armstrong GR, Bigley G, Green H, Attwood SE (2001) Cyclooxygenase-2 expression in the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 96 (4): 990–996

    PubMed  CAS  Google Scholar 

  84. Buskens CJ, Van Rees BP, Sivula A, Reitsma JB, Haglund C, Bosma PJ, Offerhaus GJ, Van Lanschot JJ, Ristimaki A (2002) Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus. Gastroenterology 122 (7): 1800–1807

    PubMed  CAS  Google Scholar 

  85. Kaur BS, Triadafilopoulos G (2002) Acid-and bile-induced PGE(2) release and hyper-proliferation in Barrett’s esophagus are COX-2 and PKC-epsilon dependent. Am J Physiol Gastrointest Liver Physiol 283 (2): G327–334

    PubMed  CAS  Google Scholar 

  86. Wambura C, Aoyama N, Shirasaka D, Sakai T, Ikemura T, Sakashita M, Maekawa S, Kuroda K, Inoue T, Ebara S et al (2002) Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis. Helicobacter 7(2): 129–138

    PubMed  CAS  Google Scholar 

  87. Jiang XH, Wong BC (2003) Cyclooxygenase-2 inhibition and gastric cancer. Curr Pharm Des 9 (27): 2281–2288

    PubMed  CAS  Google Scholar 

  88. Konturek PC, Hartwich A, Zuchowicz M, Labza H, Pierzchalski P, Karczewska E, Bielanski W, Hahn EG, Konturek SJ (2000) Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer. J Physiol Pharmacol 51 (4 Pt 1): 737–749

    PubMed  CAS  Google Scholar 

  89. Sung JJ, Leung WK, Go MY, To KF, Cheng AS, Ng EK, Chan FK (2000) Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol 157 (3): 729–735

    PubMed  CAS  Google Scholar 

  90. Walker, MM (2002) Cyclooxygenase-2 expression in early gastric cancer, intestinal metaplasia and Helicobacter pylori infection. Eur J Gastroenterol Hepatol 14 (4): 347–349

    PubMed  CAS  Google Scholar 

  91. Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M (1997) Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 57 (7): 1276–1280

    PubMed  CAS  Google Scholar 

  92. Uefuji K, Ichikura T, Mochizuki H, Shinomiya N (1998) Expression of cyclooxygenase2 protein in gastric adenocarcinoma. J Surg Oncol 69 (3): 168–172

    PubMed  CAS  Google Scholar 

  93. Ratnasinghe D, Tangrea JA, Roth MJ, Dawsey SM, Anver M, Kasprzak BA, Hu N, Wang QH, Taylor PR (1999) Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus. Oncol Rep 6 (5): 965–968

    PubMed  CAS  Google Scholar 

  94. Saukkonen K, Nieminen O, van Rees B, Vilkki S, Harkonen M, Juhola M, Mecklin JP, Sipponen P, Ristimaki A (2001) Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma. Clin Cancer Res 7 (7): 1923–1931

    PubMed  CAS  Google Scholar 

  95. Yamagata R, Shimoyama T, Fukuda S, Yoshimura T, Tanaka M, Munakata A (2002) Cyclooxygenase-2 expression is increased in early intestinal-type gastric cancer and gastric mucosa with intestinal metaplasia. Eur J Gastroenterol Hepatol 14 (4): 359–363

    PubMed  CAS  Google Scholar 

  96. Ohno R, Yoshinaga K, Fujita T, Hasegawa K, Iseki H, Tsunozaki H, Ichikawa W, Nihei Z, Sugihara K (2001) Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma. Cancer 91 (10): 1876–1881

    PubMed  CAS  Google Scholar 

  97. Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, Shiozaki H, Hori M (1999) Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol 94 (2): 451–455

    PubMed  CAS  Google Scholar 

  98. Uefuji K, Ichikura T, Mochizuki H (2001) Expression of cyclooxygenase-2 in human gastric adenomas and adenocarcinomas. J Surg Oncol 76 (1): 26–30

    PubMed  CAS  Google Scholar 

  99. Okami J, Yamamoto H, Fujiwara Y, Tsujie M, Kondo M, Noura S, Oshima S, Nagano H, Dono K, Umeshita K et al (1999) Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin Cancer Res 5 (8): 2018–2024

    PubMed  CAS  Google Scholar 

  100. Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, Soslow RA, Masferrer JL, Woerner BM, Koki AT et al (1999) Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 59 (5): 987–990

    PubMed  CAS  Google Scholar 

  101. Schlosser W, Schlosser S, Ramadani M, Gansauge F, Gansauge S, Beger HG (2002) Cyclooxygenase-2 is overexpressed in chronic pancreatitis. Pancreas 25 (1): 26–30

    PubMed  Google Scholar 

  102. Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA (1999) Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 59 (17): 4356–4362

    PubMed  CAS  Google Scholar 

  103. Niijima M, Yamaguchi T, Ishihara T, Hara T, Kato K, Kondo F, Saisho H (2002) Immunohistochemical analysis and in situ hybridization of cyclooxygenase-2 expression in intraductal papillary-mucinous tumors of the pancreas. Cancer 94 (5): 1565–1573

    PubMed  CAS  Google Scholar 

  104. Kong G, Kim EK, Kim WS, Lee KT, Lee YW, Lee JK, Paik SW, Rhee JC (2002) Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer. J Gastroenterol Hepatol 17 (8): 914–921

    PubMed  CAS  Google Scholar 

  105. Maitra A, Ashfaq R, Gunn CR, Rahman A, Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Wilentz RE (2002) Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol 118 (2): 194–201

    PubMed  CAS  Google Scholar 

  106. Kokawa A, Kondo H, Gotoda T, Ono H, Saito D, Nakadaira S, Kosuge T, Yoshida S (2001) Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer 91 (2): 333–338

    PubMed  CAS  Google Scholar 

  107. Ohike N, Morohoshi T (2001) Immunohistochemical analysis of cyclooxygenase (COX)-2 expression in pancreatic endocrine tumors: association with tumor progression and proliferation. Pathol Int 51 (10): 770–777

    PubMed  CAS  Google Scholar 

  108. Bailey, MA, EM Brunt (2002) Hepatocellular carcinoma: predisposing conditions and precursor lesions. Gastroenterol Clin North Am 31(2): 641–662

    PubMed  Google Scholar 

  109. Bae SH, Jung ES, Park YM, Kim BS, Kim BK, Kim DG, Ryu WS (2001) Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398. Clin Cancer Res 7 (5): 1410–1418

    PubMed  CAS  Google Scholar 

  110. Kondo M, Yamamoto H, Nagano H, Okami J, Ito Y, Shimizu J, Eguchi H, Miyamoto A, Dono K, Umeshita K et al (1999) Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma. Clin Cancer Res 5 (12): 4005–4012

    PubMed  CAS  Google Scholar 

  111. Koga H, Sakisaka S, Ohishi M, Kawaguchi T, Taniguchi E, Sasatomi K, Harada M, Kusaba T, Tanaka M, Kimura R et al (1999) Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology 29 (3): 688–696

    PubMed  CAS  Google Scholar 

  112. Morinaga S, Yamamoto Y, Noguchi Y, Imada T, Rino Y, Akaike M, Sugimasa Y, Takemiya S, Kameda Y, Takanashi Y (2002) Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma. J Gastroenterol Hepatol 17 (10): 1110–1116

    PubMed  CAS  Google Scholar 

  113. Nakatsugi S, Fukutake M, Takahashi M, Fukuda K, Isoi T, Taniguchi Y, Sugimura T, Wakabayashi K (1997) Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice. Jpn J Cancer Res 88 (12): 1117–1120

    PubMed  CAS  Google Scholar 

  114. Wallace JL (2001) Prostaglandin biology in inflammatory bowel disease. Gastroenterol Clin North Am 30 (4): 971–980

    PubMed  CAS  Google Scholar 

  115. Agoff SN, Brentnall TA, Crispin DA, Taylor SL, Raaka S, Haggitt RC, Reed MW, Afonina IA, Rabinovitch PS, Stevens AC et al (2000) The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. Am J Pathol 157 (3): 737–745

    PubMed  CAS  Google Scholar 

  116. Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3 (1): 28

    PubMed  Google Scholar 

  117. Anderson KE, Johnson TW, Lazovich D, Folsom AR (2002) Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J Natl Cancer Inst 94 (15): 1168–1171

    PubMed  Google Scholar 

  118. Coogan PF, Rosenberg L, Palmer JR, Strom BL, Zauber AG, Stolley PD, Shapiro S (2000) Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol Biomarkers Prey 9 (1): 119–123

    CAS  Google Scholar 

  119. Akre K, Ekstrom AM, Signorello LB, Hansson LE, Nyren O (2001) Aspirin and risk for gastric cancer: a population-based case-control study in Sweden. Br J Cancer 84 (7): 965–968

    PubMed  CAS  Google Scholar 

  120. Langman MJ, Cheng KK, Gilman EA, Lancashire RJ (2000) Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMI 320 (7250): 1642–1646

    CAS  Google Scholar 

  121. Kaur BS, Khamnehei N, Iravani M, Namburu SS, Lin O, Triadafilopoulos G (2002) Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett’s esophagus. Gastroenterology 123 (1): 60–67

    PubMed  CAS  Google Scholar 

  122. Buttar NS, Wang KK, Anderson MA, Dierkhising RA, Pacifico RJ, Krishnadath KK, Lutzke LS (2002) The effect of selective cyclooxygenase-2 inhibition in Barrett’s esophagus epithelium: an in vitro study. J Natl Cancer Inst 94 (6): 422–429

    PubMed  CAS  Google Scholar 

  123. Menezes RJ, Huber KR, Mahoney MC, Moysich KB (2002) Regular use of aspirin and pancreatic cancer risk. BMC Public Health 2 (1): 18

    PubMed  Google Scholar 

  124. Chen X, Li N, Wang S, Hong J, Fang M, Yousselfson J, Yang P, Newman RA, Lubet RA, Yang CS (2002) Aberrant arachidonic acid metabolism in esophageal adenocarcinogenesis, and the effects of sulindac, nordihydroguaiaretic acid, and alpha-difluoromethylornithine on tumorigenesis in a rat surgical model. Carcinogenesis 23(12): 2095–2102

    PubMed  CAS  Google Scholar 

  125. Buttar NS, Wang KK, Leontovich O, Westcott JY, Pacifico RJ, Anderson MA, Krishnadath KK, Lutzke LS, Burgart LJ (2002) Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett’s esophagus. Gastroenterology 122 (4): 1101–1112

    PubMed  CAS  Google Scholar 

  126. Carlton PS, Gopalakrishnan R, Gupta A, Liston BW, Habib S, Morse MA, Stoner GD (2002) Piroxicam is an ineffective inhibitor of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus. Cancer Res 62 (15): 4376–4382

    PubMed  CAS  Google Scholar 

  127. Hahm KB, Song YJ, Oh TY, Lee JS, Surh YJ, Kim YB, Yoo BM, Kim JH, Han SU, Nahm KT et al (2003) Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? J Biochem Mol Biol 36 (1): 82–94

    PubMed  CAS  Google Scholar 

  128. Furukawa F, Nishikawa A, Lee IS, Kanki K, Umemura T, Okazaki K, Kawamori T, Wakabayashi K, Hirose M (2003) A cyclooxygenase-2 inhibitor, nimesulide, inhibits postinitiation phase of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters. Int J Cancer 104 (3): 269–273

    PubMed  CAS  Google Scholar 

  129. Schuller HM, Zhang L, Weddle DL, Castonguay A, Walker K, Miller MS (2002) The cyclooxygenase inhibitor ibuprofen and the FLAP inhibitor MK886 inhibit pancreatic carcinogenesis induced in hamsters by transplacental exposure to ethanol and the tobacco carcinogen NNK. J Cancer Res Clin Oncol 128 (10): 525–532

    PubMed  CAS  Google Scholar 

  130. Wenger FA, Kilian M, Bisevac M, Khodadayan C, von Seebach M, Schimke I, Guski H, Muller JM (2002) Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters. Clin Exp Metastasis 19 (8): 681–687

    PubMed  CAS  Google Scholar 

  131. Yamamoto H, Kondo M, Nakamori S, Nagano H, Wakasa K, Sugita Y, Chang-De J, Kobayashi S, Damdinsuren B, Dono K et al (2003) JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1. Gastroenterology 125 (2): 556–571

    PubMed  CAS  Google Scholar 

  132. Nishimura G, Yanoma S, Mizuno H, Kawakami K, Tsukuda M (1999) A selective cyclooxygenase-2 inhibitor suppresses tumor growth in nude mouse xenografted with human head and neck squamous carcinoma cells. Jpn J Cancer Res 90 (10): 1152–1162

    PubMed  CAS  Google Scholar 

  133. Souza RF, Shewmake K, Beer DG, Cryer B, Spechler SJ (2000) Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res 60 (20): 5767–5772

    PubMed  CAS  Google Scholar 

  134. Sawaoka H, Kawano S, Tsuji S, Tsujii M, Gunawan ES, Takei Y, Nagano K, Hori M (1998) Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. Am J Physiol 274 (6 Pt 1): G1061–1067

    PubMed  CAS  Google Scholar 

  135. Ding XZ, Tong WG, Adrian TE (2000) Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Anticancer Res 20 (4): 2625–2631

    PubMed  CAS  Google Scholar 

  136. Tseng WW, Deganutti A, Chen MN, Saxton RE, Liu CD (2002) Selective cyclooxygenase2 inhibitor rofecoxib (Vioxx) induces expression of cell cycle arrest genes and slows tumor growth in human pancreatic cancer. J Gastrointest Surg 6(6): 838–843; discussion 844

    PubMed  Google Scholar 

  137. Chu J, Lloyd FL, Trifan OC, Knapp B, Rizzo MT (2003) Potential involvement of the cyclooxygenase-2 pathway in the regulation of tumor-associated angiogenesis and growth in pancreatic cancer. Mol Cancer Ther 2 (1): 1–7

    PubMed  CAS  Google Scholar 

  138. Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF, Hla T (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276 (21): 18563–18569

    PubMed  CAS  Google Scholar 

  139. Makitie AA, Chau M, Lim S, Viani MA, Gilbert R, Lim MS, Jordan RC (2003) Selective inhibition of cyclooxygenase 2 induces p27kip1 and skp2 in oral squamous cell carcinoma. J Otolaryngol 32 (4): 226–229

    PubMed  Google Scholar 

  140. Detjen KM, Welzel M, Wiedenmann B, Rosewicz S (2003) Nonsteroidal anti-inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell-cycle arrest. Int J Cancer 107 (5): 844–853

    PubMed  CAS  Google Scholar 

  141. Swamy MV, Herzog CR, Rao CV (2003) Inhibition of COX-2 in colon cancer cell lines by celecoxib increases the nuclear localization of active p53. Cancer Res 63 (17): 5239–5242

    PubMed  CAS  Google Scholar 

  142. Nikitakis NG, Hebert C, Lopes MA, Reynolds MA, Sauk JJ (2002) PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells. Int J Cancer 98 (6): 817–823

    PubMed  CAS  Google Scholar 

  143. Wick M, Hurteau G, Dessev C, Chan D, Geraci MW, Winn RA, Heasley LE, Nemenoff RA (2002) Peroxisome proliferator-activated receptor-gamma is a target of nonsteroidal anti-inflammatory drugs mediating cyclooxygenase-independent inhibition of lung cancer cell growth. Mol Pharmacol 62 (5): 1207–1214

    PubMed  CAS  Google Scholar 

  144. He TC, Chan TA, Vogelstein B, Kinzler KW (1999) PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99 (3): 335–345

    PubMed  CAS  Google Scholar 

  145. Hoshino T, Tsutsumi S, Tomisato W, Hwang HJ, Tsuchiya T, Mizushima T (2003) Prostaglandin E2 protects gastric mucosal cells from apoptosis via EP2 and EP4 receptor activation. J Biol Chem 278 (15): 12752–12758

    PubMed  CAS  Google Scholar 

  146. Yang H, Majno P, Morel P, Toso C, Triponez F, Oberholzer J, Mentha G, Lou J (2002) Prostaglandin E(1) protects human liver sinusoidal endothelial cell from apoptosis induced by hypoxia reoxygenation. Microvasc Res 64 (1): 94–103

    PubMed  CAS  Google Scholar 

  147. Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58 (2): 362–366

    PubMed  CAS  Google Scholar 

  148. Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B (2000) Role of BAX in the apoptotic response to anticancer agents. Science 290 (5493): 989–992

    PubMed  CAS  Google Scholar 

  149. Nzeako UC, Guicciardi ME, Yoon JH, Bronk SF, Gores GJ (2002) COX-2 inhibits Fasmediated apoptosis in cholangiocarcinoma cells. Hepatology 35 (3): 552–559

    PubMed  CAS  Google Scholar 

  150. Gately S, Kerbel R (2003) Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis. Prog Exp Tumor Res 37: 179–192

    PubMed  CAS  Google Scholar 

  151. Ben-Av P, Crofford LJ, Wilder RL, Hla T (1995) Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 372 (1): 83–87

    CAS  Google Scholar 

  152. Leung WK, To KF, Go MY, Chan KK, Chan FK, Ng EK, Chung SC, Sung JJ (2003) Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. Int J Oncol 23 (5): 1317–1322

    PubMed  CAS  Google Scholar 

  153. Jones MK, Szabo IL, Kawanaka H, Husain SS, Tarnawski AS (2002) von Hippel Lindau tumor suppressor and HIF-lalpha: new targets of NSAIDs inhibition of hypoxiainduced angiogenesis. FASEB J 16 (2): 264–266

    PubMed  CAS  Google Scholar 

  154. Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M (1999) Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 79 (12): 1469–1477

    PubMed  CAS  Google Scholar 

  155. Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL (2002) Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 62 (3): 625–631

    PubMed  CAS  Google Scholar 

  156. Sheng H, Shao J, Washington MK, DuBois RN (2001) Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276 (21): 18075–18081

    PubMed  CAS  Google Scholar 

  157. Dohadwala M, Luo J, Zhu L, Lin Y, Dougherty GJ, Sharma S, Huang M, Pold M, Batra RK, Dubinett SM (2001) Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. J Biol Chem 276 (24): 20809–20812

    PubMed  CAS  Google Scholar 

  158. Marx J (2001) Cancer research. Anti-inflammatories inhibit cancer growth – but how? Science 291(5504): 581–582

    PubMed  CAS  Google Scholar 

  159. Zhang X, Morham SG, Langenbach R, Young DA (1999) Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med 190 (4): 451–459

    PubMed  CAS  Google Scholar 

  160. Eibl G, Reber HA, Wente MN, Hines OJ (2003) The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas 26 (1): 33–41

    PubMed  CAS  Google Scholar 

  161. Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI, Rigas B (1996) Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem Pharmacol 52 (2): 237–245

    PubMed  CAS  Google Scholar 

  162. Rice PL, Kelloff J, Sullivan H, Driggers LJ, Beard KS, Kuwada S, Piazza G, Ahnen DJ (2003) Sulindac metabolites induce caspase-and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells. Mol Cancer Ther 2 (9): 885–892

    PubMed  CAS  Google Scholar 

  163. Piazza GA, Alberts DS, Hixson LJ, Paranka NS, Li H, Finn T, Bogert C, Guillen JM, Brendel K, Gross PH et al (1997) Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res 57 (14): 2909–2915

    PubMed  CAS  Google Scholar 

  164. Liu JJ, Wang JY, Hertervig E, Nilsson A, Duan RD (2002) Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells. Anticancer Res 22 (1A): 263–266

    PubMed  CAS  Google Scholar 

  165. Yamamoto Y, Yin MJ, Lin KM, Gaynor RB (1999) Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274 (38): 27307–27314

    PubMed  CAS  Google Scholar 

  166. Arico S, Pattingre S, Bauvy C, Gane P, Barbat A, Codogno P, Ogier-Denis E (2002) Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 277 (31): 27613–27621

    PubMed  CAS  Google Scholar 

  167. Jiang XH, Lam SK, Lin MC, Jiang SH, Kung HF, Slosberg ED, Soh JW, Weinstein IB, Wong BC (2002) Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway. Oncogene 21 (39): 6113–6122

    PubMed  CAS  Google Scholar 

  168. Hsueh CT, Chiu CF, Kelsen DP, Schwartz GK (2000) Selective inhibition of cyclooxygenase-2 enhances mitomycin-C-induced apoptosis. Cancer Chemother Pharmacol 45 (5): 389–396

    PubMed  CAS  Google Scholar 

  169. Yip-Schneider MT, Sweeney CJ, Jung SH, Crowell PL, Marshall MS (2001) Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells. J Pharmacol Exp Ther 298 (3): 976–985

    PubMed  CAS  Google Scholar 

  170. Sugiura T, Saikawa Y, Kubota T, Suganuma K, Otani Y, Watanabe M, Kumai K, Kitajima M (2003) Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo. In Vivo 17 (3): 229–233

    PubMed  CAS  Google Scholar 

  171. Altorki NK, Keresztes RS, Port JL, Libby DM, Korst RJ, Flieder DB, Ferrara CA, Yankelevitz DF, Subbaramaiah K, Pasmantier MW et al (2003) Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. J Clin Oncol 21 (14): 2645–2650

    PubMed  CAS  Google Scholar 

  172. Crane CH, Mason K, Janjan NA, Milas L (2003) Initial experience combining cyclooxygenase-2 inhibition with chemoradiation for locally advanced pancreatic cancer. Am J Clin Oncol 26 (4): S81–84

    PubMed  Google Scholar 

  173. Becerra CR, Frenkel EP, Ashfaq R, Gaynor RB (2003) Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study. Int J Cancer 105 (6): 868–872

    PubMed  CAS  Google Scholar 

  174. Turini ME, DuBois RN (2002) Primary prevention: phytoprevention and chemoprevention of colorectal cancer. Hematol Oncol Clin North Am 16 (4): 811–840

    PubMed  Google Scholar 

  175. Fennerty MB (2002) Does chemoprevention of Barrett’s esophagus using acid suppression and/or COX-2 inhibition prevent neoplastic progression? Rev Gastroenterol Disord 2 (Suppl 2): S30–S37

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    John P. Lynch

  2. Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Gary R. Lichtenstein

Authors
  1. John P. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary R. Lichtenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. TAP Pharmaceuticals, 675 North Field Dr., Lake Forest, IL, 60045, USA

    Douglas W. Morgan

  2. IPF PharmaCeuticals, Feodor-Lynen-Strasse 31, Hannover, 30625, Germany

    Ulf J. Forssmann

  3. Oncology Research, Centocor, 200 Great Valley Parkway, Malvern, PA, 19355, USA

    Marian T. Nakada

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Basel AG

About this chapter

Cite this chapter

Lynch, J.P., Lichtenstein, G.R. (2004). Cyclooxygenase activity in gastrointestinal cancer development and progression: prospects as a therapeutic target. In: Morgan, D.W., Forssmann, U.J., Nakada, M.T. (eds) Cancer and Inflammation. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7861-6_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7861-6_7

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9600-9

  • Online ISBN: 978-3-0348-7861-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation