Skip to main content
Log in

Cancer and the Cyclo-Oxygenase Enzyme

Implications for Treatment and Prevention

  • Review Article
  • Published:
American Journal of Cancer

Abstract

The cyclo-oxygenase (COX) metabolic pathway and prostaglandin (PG) production appear to play a causal role in the promotion and progression of human cancers. COX-1 and COX-2 are the enzymes that convert arachidonic acid into PGs and thromboxanes. COX-2 has received a great deal of attention recently because it is commonly overexpressed in a wide range of cancers and precancerous lesions (e.g. in colon, lung, prostate and breast), and elevated production of prostanoids (particularly prostaglandin [PGE2]) via COX-2 is associated with several pro-carcinogenic effects including: increased proliferation, apoptosis resistance, host immunosuppression, tumor neoangiogenesis, and increased metastatic potential. Inhibitors of COX-1 and COX-2 (e.g. aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. celecoxib and rofecoxib) have shown cancer preventative efficacy in epidemiological studies, experimental studies in laboratory animals, and in human clinical trials. Because of their improved tolerability profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. This article attempts to comprehensively review the role of the COX pathway in tumorigenesis, and the mechanisms, safety, and efficacy of COX nonselective and COX-2 selective inhibitors for cancer chemopreventive and chemotherapeutic applications.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table I. (continued)
Table II
Table II. (continued)
Table II. (continued)
Table III
Table IV
Table V
Table VI
Table VII
Table VIII
Table IX
Table IX. (continued)

Similar content being viewed by others

References

  1. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000 Jan 1; 69(1): 145–82

    Article  CAS  PubMed  Google Scholar 

  2. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998; 38: 97–120

    Article  CAS  PubMed  Google Scholar 

  3. Needleman P, Turk J, Jakschik BA, et al. Arachidonic acid metabolism. Annu Rev Biochem 1986; 55: 69–102

    Article  CAS  PubMed  Google Scholar 

  4. Lupulescu A. Prostaglandins: their inhibitors and cancer. Prostaglandins Leukot Essent Fatty Acids 1996 Feb; 54(2): 83–94

    Article  CAS  PubMed  Google Scholar 

  5. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996; 271(52): 33157–60

    Article  CAS  PubMed  Google Scholar 

  6. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 1996; 270 (3 Pt 1): G393–400

    CAS  PubMed  Google Scholar 

  7. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Ada 1996; 1299(1): 125–40

    Article  Google Scholar 

  8. Howe LR, Subbaramaiah K, Brown AM, et al. Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 2001 Jun; 8(2): 97–114

    Article  CAS  PubMed  Google Scholar 

  9. Howe LR, Crawford HC, Subbaramaiah K, et al. PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 2001 June 8; 276(23): 20108–20115

    Article  CAS  PubMed  Google Scholar 

  10. Xie W, Herschman HR. V-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J Biol Chem 1995; 270(46): 27622–8

    Article  CAS  PubMed  Google Scholar 

  11. Subbaramiah K, Norton L, Gerald W, et al. Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem 2002; 277(21): 18649–57

    Article  CAS  Google Scholar 

  12. Sheng H, Shao J, Morrow JD, et al. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 1998; 58(2): 362–6

    CAS  PubMed  Google Scholar 

  13. Vadlamudi R, Mandai M, Adam L, et al. Regulation of cyclooxygenase-2 pathway by HER2 receptor. Oncogene 1999; 18(2): 305–14

    Article  CAS  PubMed  Google Scholar 

  14. Chen G, Wilson R, McKillop JH, et al. The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells. Immunol Invest 1994; 23(4–5): 269–79

    Article  CAS  PubMed  Google Scholar 

  15. Subbaramaiah K, Telang N, Ramonetti JT, et al. Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells. Cancer Res 1996; 56(19): 4424–9

    CAS  PubMed  Google Scholar 

  16. Subbarayan V, Sabichi AL, Llansa N, et al. Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis factor-alpha in normal and malignant prostate cells. Cancer Res 2001; 61(6): 2720–6

    CAS  PubMed  Google Scholar 

  17. Herschman HR. Function and regulation of prostaglandin synthase 2. Adv Exp Med Biol 1999; 469: 3–8

    Article  CAS  PubMed  Google Scholar 

  18. Ramsay RG, Friend A, Vizantios Y, et al. Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB. Cancer Res 2000 Apr 1; 60(7): 1805–9

    CAS  PubMed  Google Scholar 

  19. Gorgoni B, Caivano M, Arizmendi C, et al. The transcription factor C/EBPbeta is essential for inducible expression of the cox-2 gene in macrophages but not in fibroblasts. J Biol Chem 2001 Nov 2; 276(44): 40769–77

    Article  CAS  PubMed  Google Scholar 

  20. Xie W, Herschman HR. Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J Biol Chem 1996; 271(49): 31742–8

    Article  CAS  PubMed  Google Scholar 

  21. Subbaramaiah K, Chung WJ, Dannenberg AJ. Ceramide regulates the transcription of cyclooxygenase-2: evidence for involvement of extracellular signal-regulated kinase/c-Jun N-terminal kinase and p38 mitogen-activated protein kinase pathways. J Biol Chem 1998 Dec 4; 273(49): 32943–9

    Article  CAS  PubMed  Google Scholar 

  22. Chen C-C, Sun Y-T, Chen J-J, et al. Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression via sequential activation of ceramide-dependent mitogen-activated protein kinases, and I-kappaB kinase 1/2 in human alveolar epithelial cells. Mol Pharmacol 2001 Mar 1; 59(3): 493–500

    Article  CAS  PubMed  Google Scholar 

  23. Srivastava SK, Tetsuka T, Daphna-Iken D, et al. IL-1 beta stabilizes COX II mRNA in renal mesangial cells: role of 3′-untranslated region. Am J Physiol 1994 Sep; 267 (3 Pt 2): F504–8

    CAS  PubMed  Google Scholar 

  24. Cok SJ, Morrison AR. The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency. J Biol Chem 2001 Jun 22; 276(25): 23179–85

    Article  CAS  PubMed  Google Scholar 

  25. Dixon DA, Tolley ND, King PH, et al. Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest 2001 Dec; 108(11): 1657–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sheng H, Shao J, Dixon DA, et al. Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA. J Biol Chem 2000 Mar 3; 275(9): 6628–35

    Article  CAS  PubMed  Google Scholar 

  27. Eberhart CE, Coffey RJ, Radhika A, et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107(4): 1183–8

    Article  CAS  PubMed  Google Scholar 

  28. Kargman SL, O’Neill GP, Vickers PJ, et al. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995; 55(12): 2556–9

    CAS  PubMed  Google Scholar 

  29. Kutchera W, Jones DA, Matsunami N, et al. Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc Natl Acad Sci U S A 1996; 93(10): 4816–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gustafson-Svard C, Lilja I, Hallbook O, et al. Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats. Gut 1996; 38(1): 79–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fujita T, Matsui M, Takaku K, et al. Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas. Cancer Res 1998; 58(21): 4823–6

    CAS  PubMed  Google Scholar 

  32. Maekawa M, Sugano K, Sano H, et al. Increased expression of cyclooxygenase-2 to -1 in human colorectal cancers and adenomas, but not in hyperplastic polyps. Jpn J Clin Oncol 1998; 28(7): 421–6

    Article  CAS  PubMed  Google Scholar 

  33. Sinicrope FA, Lemoine M, Xi L, et al. Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers. Gastroenterology 1999; 117(2): 350–8

    Article  CAS  PubMed  Google Scholar 

  34. Sheehan KM, Sheahan K, O’Donoghue DP, et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 1999; 282(13): 1254–7

    Article  CAS  PubMed  Google Scholar 

  35. Shattuck-Brandt RL, Lamps LW, Heppner Goss KJ, et al. Differential expression of matrilysin and cyclooxygenase-2 in intestinal and colorectal neoplasms. Mol Carcinog 1999; 24(3): 177–87

    Article  CAS  PubMed  Google Scholar 

  36. Sakuma K, Fujimori T, Hirabayashi K, et al. Cyclooxygenase (COX)-2 immuno-reactivity and relationship to p53 and Ki-67 expression in colorectal cancer. J Gastroenterol 1999; 34(2): 189–94

    Article  CAS  PubMed  Google Scholar 

  37. Hao X, Bishop AE, Wallace M, et al. Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. J Pathol 1999; 187(3): 295–301

    Article  CAS  PubMed  Google Scholar 

  38. Bamba H, Ota S, Kato A, et al. High expression of cyclooxygenase-2 in macrophages of human colonic adenoma. Int J Cancer 1999; 83(4): 470–5

    Article  CAS  PubMed  Google Scholar 

  39. Dimberg J, Samuelsson A, Hugander A, et al. Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut 1999; 45(5): 730–2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tomozawa S, Tsuno NH, Sunami E, et al. Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer. Br J Cancer 2000; 83(3): 324–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Masunaga R, Kohno H, Dhar DK, et al. Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res 2000; 6(10): 4064–8

    CAS  PubMed  Google Scholar 

  42. Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 2000; 89(12): 2637–45

    Article  CAS  PubMed  Google Scholar 

  43. Hull MA, Fenwick SW, Chappie KS, et al. Cyclooxygenase-2 expression in colorectal cancer liver metastases. Clin Exp Metastasis 2000; 18(1): 21–7

    Article  CAS  PubMed  Google Scholar 

  44. Fujita M, Fukui H, Kusaka T, et al. Relationship between cyclooxygenase-2 expression and K-ras gene mutation in colorectal adenomas. J Gastroenterol Hepatol 2000; 15(11): 1277–81

    CAS  PubMed  Google Scholar 

  45. Chappie KS, Cartwright EJ, Hawcroft G, et al. Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 2000; 156(2): 545–53

    Article  Google Scholar 

  46. Arbabi S, Rosengart MR, Garcia I, et al. Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer. J Surg Res 2001; 97(1): 60–4

    Article  CAS  PubMed  Google Scholar 

  47. Chen WS, Wei SJ, Liu JM, et al. Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac. Int J Cancer 2001; 91(6): 894–9

    Article  CAS  PubMed  Google Scholar 

  48. Yoshimura R, Sano H, Mitsuhashi M, et al. Expression of cyclooxygenase-2 in patients with bladder carcinoma. J Urol 2001 May; 165(5): 1468–72

    Article  CAS  PubMed  Google Scholar 

  49. Bostrom PJ, Uotila P, Rajala P, et al. Interferon-alpha inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2 expression in bladder cancer cells in vitro. Urol Res 2001; 29(1): 20–4

    Article  CAS  PubMed  Google Scholar 

  50. Komhoff M, Guan Y, Shappell HW, et al. Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas. Am J Pathol 2000; 157(1): 29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mohammed SI, Knapp DW, Bostwick DG, et al. Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999; 59(22): 5647–50

    CAS  PubMed  Google Scholar 

  52. Ristimaki A, Sivula A, Lundin J, et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 2002 Feb 1; 62(3): 632–5

    CAS  PubMed  Google Scholar 

  53. Hwang D, Scollard D, Byrne J, et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 1998; 90(6): 455–60

    Article  CAS  PubMed  Google Scholar 

  54. Deininger MH, Weiler M, Streffer J, et al. Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo. Acta Neuropathol (Berl) 1999; 98(3): 240–4

    Article  CAS  Google Scholar 

  55. Joki T, Heese O, Nikas DC, et al. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 2000; 60(17): 4926–31

    CAS  PubMed  Google Scholar 

  56. Karim MM, Hayashi Y, Inoue M, et al. Cox-2 expression in retinoblastoma. Am J Ophthalmol 2000; 129(3): 398–401

    Article  CAS  PubMed  Google Scholar 

  57. Shono T, Tofilon PJ, Bruner JM, et al. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res 2001 Jun 1; 61(11): 4375–81

    CAS  PubMed  Google Scholar 

  58. Ferrandina G, Lauriola L, Distefano MG, et al. Increased Cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol 2002 Feb 15; 20(4): 973–81

    Article  CAS  PubMed  Google Scholar 

  59. Gaffney DK, Holden J, Davis M, et al. Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy. Int J Radiat Oncol Biol Phys 2001; 49(5): 1213–7

    Article  CAS  PubMed  Google Scholar 

  60. Kulkarni S, Rader JS, Zhang F, et al. Cyclooxygenase-2 is overexpressed in human cervical cancer. Clin Cancer Res 2001; 7(2): 429–34

    CAS  PubMed  Google Scholar 

  61. Ryu HS, Chang KH, Yang HW, et al. High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion. Gynecol Oncol 2000; 76(3): 320–5

    Article  CAS  PubMed  Google Scholar 

  62. Kandil HM, Tanner G, Smalley W, et al. Cyclooxygenase-2 expression in Barrett’s esophagus. Dig Dis Sci 2001; 46(4): 785–9

    Article  CAS  PubMed  Google Scholar 

  63. Morris CD, Armstrong GR, Bigley G, et al. Cyclooxygenase-2 expression in the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001; 96(4): 990–6

    CAS  PubMed  Google Scholar 

  64. Shirvani VN, Ouatu-Lascar R, Kaur BS, et al. Cyclooxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: ex vivo induction by bile salts and acid exposure. Gastroenterology 2000; 118(3): 487–96

    Article  CAS  PubMed  Google Scholar 

  65. Zimmermann KC, Sarbia M, Weber AA, et al. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 1999; 59(1): 198–204

    CAS  PubMed  Google Scholar 

  66. Wilson KT, Fu S, Ramanujam KS, et al. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res 1998; 58(14): 2929–34

    CAS  PubMed  Google Scholar 

  67. Kawabe A, Shimada Y, Uchida S, et al. Expression of Cyclooxygenase-2 is associated with carcinogenesis of the lower part of thoracic esophageal squamous cell carcinoma and p53 expression. Oncology 2002; 62(1): 46–54

    Article  CAS  PubMed  Google Scholar 

  68. Ratnasinghe D, Tangrea J, Roth MJ, et al. Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anticancer Res 1999; 19(1A): 171–4

    CAS  PubMed  Google Scholar 

  69. van Rees BP, Saukkonen K, Ristimaki A, et al. Cyclooxygenase-2 expression during carcinogenesis in the human stomach. J Pathol 2002 Feb; 196(2): 171–9

    Article  CAS  PubMed  Google Scholar 

  70. Rajnakova A, Moochhala S, Goh PM, et al. Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer. Cancer Lett 2001 Oct 30; 172(2): 177–85

    Article  CAS  PubMed  Google Scholar 

  71. Akhtar M, Cheng Y, Magno RM, et al. Promoter methylation regulates helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res 2001 Mar 1; 61(6): 2399–403

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  73. Ohno R, Yoshinaga K, Fujita T, et al. Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma. Cancer 2001; 91(10): 1876–81

    Article  CAS  PubMed  Google Scholar 

  74. Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res 2000; 6(1): 135–8

    CAS  PubMed  Google Scholar 

  75. Lim HY, Joo HJ, Choi JH, et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 2000; 6(2): 519–25

    CAS  PubMed  Google Scholar 

  76. Ratnasinghe D, Tangrea JA, Roth MJ, et al. Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus. Oncol Rep 1999; 6(5): 965–8

    CAS  PubMed  Google Scholar 

  77. Yamamoto H, Itoh F, Fukushima H, et al. Overexpression of cyclooxygenase-2 protein is less frequent in gastric cancers with microsatellite instability. Int J Cancer 1999; 84(4): 400–3

    Article  CAS  PubMed  Google Scholar 

  78. Murata H, Kawano S, Tsuji S, et al. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol 1999; 94(2): 451–5

    Article  CAS  PubMed  Google Scholar 

  79. Uefuji K, Ichikura T, Mochizuki H, et al. Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol 1998; 69(3): 168–72

    Article  CAS  PubMed  Google Scholar 

  80. Soydan AS, Gaffen JD, Weech PK, et al. Cytosolic phospholipase A2, cyclo-oxygenases and arachidonate in human stomach tumours. Eur J Cancer 1997; 33(9): 1508–12

    Article  CAS  PubMed  Google Scholar 

  81. Ristimaki A, Honkanen N, Jankala H, et al. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997; 57(7): 1276–80

    CAS  PubMed  Google Scholar 

  82. Bae SH, Jung ES, Park YM, et al. 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 2001; 7(5): 1410–8

    CAS  PubMed  Google Scholar 

  83. Koga H, Sakisaka S, Ohishi M, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology 1999; 29(3): 688–96

    Article  CAS  PubMed  Google Scholar 

  84. Kondo M, Yamamoto H, Nagano H, et al. Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma. Clin Cancer Res 1999; 5(12): 4005–12

    CAS  PubMed  Google Scholar 

  85. Rahman MA, Dhar DK, Yamaguchi E, et al. Coexpression of inducible nitric oxide synthase and cox-2 in hepatocellular carcinoma and surrounding liver: possible involvement of cox-2 in the angiogenesis of hepatitis c virus-positive cases. Clin Cancer Res 2001; 7(5): 1325–32

    CAS  PubMed  Google Scholar 

  86. Shiota G, Okubo M, Noumi T, et al. Cyclooxygenase-2 expression in hepatocellular carcinoma. Hepatogastroenterology 1999; 46(25): 407–12

    CAS  PubMed  Google Scholar 

  87. Wolff H, Saukkonen K, Anttila S, et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 1998; 58(22): 4997–5001

    CAS  PubMed  Google Scholar 

  88. Yoshimatsu K, Altorki NK, Golijanin D, et al. Inducible prostaglandin E synthase is overexpressed in non-small cell lung cancer. Clin Cancer Res 2001 Sep; 7(9): 2669–74

    CAS  PubMed  Google Scholar 

  89. Dohadwala M, Luo J, Zhu L, et al. Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. J Biol Chem 2001; 276: 20809–12

    Article  CAS  PubMed  Google Scholar 

  90. Khuri FR, Wu H, Lee JJ, et al. Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 2001; 7(4): 861–7

    CAS  PubMed  Google Scholar 

  91. Hosomi Y, Yokose T, Hirose Y, et al. Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung. Lung Cancer 2000; 30(2): 73–81

    Article  CAS  PubMed  Google Scholar 

  92. Ochiai M, Oguri T, Isobe T, et al. Cyclooxygenase-2 (COX-2) mRNA expression levels in normal lung tissues and non-small cell lung cancers. Jpn J Cancer Res 1999; 90(12): 1338–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Watkins DN, Lenzo JC, Segal A, et al. Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer. Eur Respir J 1999; 14(2): 412–8

    Article  CAS  PubMed  Google Scholar 

  94. Achiwa H, Yatabe Y, Hida T, et al. Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas. Clin Cancer Res 1999; 5(5): 1001–5

    CAS  PubMed  Google Scholar 

  95. Hida T, Yatabe Y, Achiwa H, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 1998; 58(17): 3761–4

    CAS  PubMed  Google Scholar 

  96. Huang M, Stolina M, Sharma S, et al. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 1998; 58(6): 1208–16

    CAS  PubMed  Google Scholar 

  97. Merati K, Said SM, Andea A, et al. Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters. Am J Clin Oncol 2001 Oct; 24(5): 447–52

    Article  CAS  PubMed  Google Scholar 

  98. Kokawa A, Kondo H, Gotoda T, et al. Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer 2001; 91(2): 333–8

    Article  CAS  PubMed  Google Scholar 

  99. Yip-Schneider MT, Barnard DS, Billings SD, et al. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis 2000; 21(2): 139–46

    Article  CAS  PubMed  Google Scholar 

  100. Molina MA, Sitja-Arnau M, Lemoine MG, et al. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 1999; 59(17): 4356–62

    CAS  PubMed  Google Scholar 

  101. Okami J, Yamamoto H, Fujiwara Y, et al. Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin Cancer Res 1999; 5(8): 2018–24

    CAS  PubMed  Google Scholar 

  102. Tucker ON, Dannenberg AJ, Yang EK, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999; 59(5): 987–90

    CAS  PubMed  Google Scholar 

  103. Uotila P, Valve E, Martikainen P, et al. Increased expression of cyclooxygenase-2 and nitric oxide synthase-2 in human prostate cancer. Urol Res 2001; 29(1): 23–8

    Article  CAS  PubMed  Google Scholar 

  104. Tanji N, Kikugawa T, Yokoyama M. Immunohistochemical study of cyclooxygenases in prostatic adenocarcinoma; relationship to apoptosis and Bcl-2 protein expression. Anticancer Res 2000; 20(4): 2313–9

    CAS  PubMed  Google Scholar 

  105. Madaan S, Abel PD, Chaudhary KS, et al. Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment. BJU Int 2000; 86(6): 736–41

    Article  CAS  PubMed  Google Scholar 

  106. Kirschenbaum A, Klausner AP, Lee R, et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate. Urology 2000; 56(4): 671–6

    Article  CAS  PubMed  Google Scholar 

  107. Gupta S, Srivastava M, Ahmad N, et al. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 2000; 42(1): 73–8

    Article  CAS  PubMed  Google Scholar 

  108. Yoshimura R, Sano H, Masuda C, et al. Expression of cyclooxygenase-2 in prostate carcinoma. Cancer 2000; 89(3): 589–96

    Article  CAS  PubMed  Google Scholar 

  109. Tjandrawinata RR, Dahiya R, Hughes-Fulford M. Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells. Br J Cancer 1997; 75(8): 1111–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Peng JP, Su CY, Chang HC, et al. Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the hypopharynx. Hum Pathol 2002 Jan; 33(1): 100–4

    Article  CAS  PubMed  Google Scholar 

  111. Chan G, Boyle JO, Yang EK, et al. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 1999; 59(5): 991–4

    CAS  PubMed  Google Scholar 

  112. Gallo O, Franchi A, Magnelli L, et al. Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer: implications for tumor angiogenesis and metastasis. Neoplasia 2001; 3(1): 53–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Nathan CA, Leskov IL, Lin M, et al. COX-2 expression in dysplasia of the head and neck: correlation with elF4E. Cancer 2001 Oct 1; 92(7): 1888–95

    Article  CAS  PubMed  Google Scholar 

  114. Higashi Y, Kanekura T, Kanzaki T. Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: evidence for growth suppression by inhibiting COX-2 expression. Int J Cancer 2000; 86(5): 667–71

    Article  CAS  PubMed  Google Scholar 

  115. Muller-Decker K, Reinerth G, Krieg P, et al. Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin. Int J Cancer 1999; 82(5): 648–56

    Article  CAS  PubMed  Google Scholar 

  116. Buckman SY, Gresham A, Hale P, et al. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 1998; 19(5): 723–9

    Article  CAS  PubMed  Google Scholar 

  117. Denkert C, Kobel M, Berger S, et al. Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 2001 Jan 1; 61(1): 303–8

    CAS  PubMed  Google Scholar 

  118. Salmenkivi K, Haglund C, Ristimaki A, et al. Increased expression of cyclooxygenase-2 in malignant pheochromocytomas. J Clin Endocrinol Metab 2001 Nov; 86(11): 5615–9

    Article  CAS  PubMed  Google Scholar 

  119. Specht MC, Tucker ON, Hocever M, et al. Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 2002 Jan; 87(1): 358–63

    Article  CAS  PubMed  Google Scholar 

  120. Gaffney DK, Holden J, Zempolich K, et al. Elevated COX-2 expression in cervical carcinoma: reduced cause-specific survival and pelvic control. Am J Clin Oncol 2001 Oct; 24(5): 443–6

    Article  CAS  PubMed  Google Scholar 

  121. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87(5): 803–9

    Article  CAS  PubMed  Google Scholar 

  122. Williams CS, Tsujii M, Reese J, et al. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 2000; 105(11): 1589–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Chulada PC, Thompson MB, Mahler JF, et al. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 2000; 60(17): 4705–8

    CAS  PubMed  Google Scholar 

  124. Neufang G, Furstenberger G, Heidt M, et al. Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci U S A 2001 Jun 19; 98(13): 7629–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998; 93(5): 705–16

    Article  CAS  PubMed  Google Scholar 

  126. Grossman EM, Longo WE, Panesar N, et al. The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells. Carcinogenesis 2000; 21(7): 1403–9

    Article  CAS  PubMed  Google Scholar 

  127. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995; 83(3): 493–501

    Article  CAS  PubMed  Google Scholar 

  128. Nolan RD, Danilowicz RM, Eling TE. Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. Mol Pharmacol 1988 Jun; 33(6): 650–6

    CAS  PubMed  Google Scholar 

  129. Imagawa W, Bandyopadhyay GK, Wallace D, et al. Growth stimulation by PGE2 and EGF activates cyclic AMP-dependent and -independent pathways in primary cultures of mouse mammary epithelial cells. J Cell Physiol 1988 Jun; 135(3): 509–15

    Article  CAS  PubMed  Google Scholar 

  130. McKenzie KE, Bandyopadhyay GK, Imagawa W, et al. Omega-3 and omega-6 fatty acids and PGE2 stimulate the growth of normal but not tumor mouse mammary epithelial cells: evidence for alterations in the signaling pathways in tumor cells. Prostaglandins Leukot Essent Fatty Acids 1994 Dec; 51(6): 437–43

    Article  CAS  PubMed  Google Scholar 

  131. Marnett LJ. Aspirin and related nonsteroidal anti-inflammatory drugs as chemopreventive agents against colon cancer. Prev Med 1995; 24(2): 103–6

    Article  CAS  PubMed  Google Scholar 

  132. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis 2001 Jan; 22(1): 5–10

    Article  CAS  PubMed  Google Scholar 

  133. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990; 82(1): 4–6

    Article  CAS  PubMed  Google Scholar 

  134. Koki AT, Leahy KM, Masferrer JL. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin Investig Drugs 1999; 8(10): 1623–38

    Article  CAS  PubMed  Google Scholar 

  135. Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 1997; 94(7): 3336–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Cianchi F, Cortesini C, Bechi P, et al. Up-regulation of cyclooxygenase-2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 2001 Dec; 121(6): 1339–47

    Article  CAS  PubMed  Google Scholar 

  137. Anderson WF, Umar A, Viner JL, et al. The role of cyclooxygenase inhibitors in cancer prevention. Curr Pharm Des 2002; 8: 99–110

    Article  Google Scholar 

  138. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988; 48(15): 4399–404

    CAS  PubMed  Google Scholar 

  139. Thun MJ, Namboodiri MM, Heath Jr CW. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 1991; 325(23): 1593–6

    Article  CAS  PubMed  Google Scholar 

  140. Thun MJ, Namboodiri MM, Calle EE, et al. Aspirin use and risk of fatal cancer. Cancer Res 1993; 53(6): 1322–7

    CAS  PubMed  Google Scholar 

  141. Giovannucci E, Rimm EB, Stampfer MJ, et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 1994; 121(4): 241–6

    Article  CAS  PubMed  Google Scholar 

  142. Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995; 333(10): 609–14

    Article  CAS  PubMed  Google Scholar 

  143. Garcia-Rodriguez LA, Heuerta-Alvarez C. Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 2001; 12: 88–93

    Article  CAS  PubMed  Google Scholar 

  144. Garcia-Rodriguez LA, Huerta-Alvarez C. Reduced incidence of colorectal adenoma among long-term users of nonsteroidal antiinflammatory drugs: a pooled analysis of published studies and a new population-based study. Epidemiology 2000; 11(4): 376–81

    Article  CAS  PubMed  Google Scholar 

  145. Giovannucci E. The prevention of colorectal cancer by aspirin use. Biomed Pharmacother 1999; 53(7): 303–8

    Article  CAS  PubMed  Google Scholar 

  146. Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 2002 Feb 20; 94(4): 252–66

    Article  CAS  PubMed  Google Scholar 

  147. Paganini-Hill A. Aspirin and colorectal cancer: the Leisure World cohort revisited. Prev Med 1995; 24(2): 113–5

    Article  CAS  PubMed  Google Scholar 

  148. Sturmer T, Glynn RJ, Lee IM, et al. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians’ Health Study. Ann Intern Med 1998; 128(9): 713–20

    Article  CAS  PubMed  Google Scholar 

  149. Peleg II, Lubin MF, Cotsonis GA, et al. Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia. Dig Dis Sci 1996; 41(7): 1319–26

    Article  CAS  PubMed  Google Scholar 

  150. Sandler RS, Galanko JC, Murray SC, et al. Aspirin and nonsteroidal anti-inflammatory agents and risk for colorectal adenomas. Gastroenterology 1998; 114(3): 441–7

    Article  CAS  PubMed  Google Scholar 

  151. Breuer-Katschinski B, Nemes K, Rump B, et al. Long-term use of nonsteroidal antiinflammatory drugs and the risk of colorectal adenomas: the Colorectal Adenoma Study Group. Digestion 2000; 61(2): 129–34

    Article  CAS  PubMed  Google Scholar 

  152. Martinez ME, McPherson RS, Levin B, et al. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of colorectal adenomatous polyps among endoscoped individuals. Cancer Epidemiol Biomarkers Prev 1995; 4(7): 703–7

    CAS  PubMed  Google Scholar 

  153. Suh O, Mettlin C, Petrelli NJ. Aspirin use, cancer, and polyps of the large bowel. Cancer 1993; 72(4): 1171–7

    Article  CAS  PubMed  Google Scholar 

  154. Logan RF, Little J, Hawtin PG, et al. Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. BMJ 1993; 307(6899): 285–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Tangrea JA, Albert PS, Lanza E, et al. Non-steroidal anti-inflammatory drug use is associated with reduced risk of colorectal adenomas: a prospective study [abstract]. Proc AACR 2001 Mar; 42: 177

    Google Scholar 

  156. Greenberg ER, Baron JA, Freeman DH, et al. Reduced risk of large-bowel adenomas among aspirin users: the Polyp Prevention Study Group. J Natl Cancer Inst 1993; 85(11): 912–6

    Article  CAS  PubMed  Google Scholar 

  157. Pinczowski D, Ekbom A, Baron J, et al. Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study. Gastroenterology 1994; 107(1): 117–20

    Article  CAS  PubMed  Google Scholar 

  158. Muscat JE, Stellman SD, Wynder EL. Nonsteroidal antiinflammatory drugs and colorectal cancer. Cancer 1994; 74(7): 1847–54

    Article  CAS  PubMed  Google Scholar 

  159. Peleg II, Maibach HT, Brown SH, et al. Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer. Arch Intern Med 1994; 154(4): 394–9

    Article  CAS  PubMed  Google Scholar 

  160. Freedman AN, Michalek AM, Weiss HA, et al. Aspirin use and p53 expression in colorectal cancer. Cancer Detect Prev 1998; 22(3): 213–8

    Article  CAS  PubMed  Google Scholar 

  161. Neugut AI, Rosenberg DJ, Ahsan H, et al. Association between coronary heart disease and cancers of the breast, prostate, and colon. Cancer Epidemiol Biomarkers Prev 1998; 7(10): 869–73

    CAS  PubMed  Google Scholar 

  162. Bucher C, Jordan P, Nickeleit V, et al. Relative risk of malignant tumors in analgesic abusers: effects of long-term intake of aspirin. Clin Nephrol 1999; 51(2): 67–72

    CAS  PubMed  Google Scholar 

  163. La Vecchia C, Negri E, Franceschi S, et al. Aspirin and colorectal cancer. Br J Cancer 1997; 76(5): 675–7

    Article  PubMed  PubMed Central  Google Scholar 

  164. Friedman GD, Coates AO, Potter JD, et al. Drugs and colon cancer. Pharmacoepidemiol Drug Safety 1998; 7: 99–106

    Article  CAS  Google Scholar 

  165. Rosenberg L, Palmer JR, Zauber AG, et al. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 1991; 83(5): 355–8

    Article  CAS  PubMed  Google Scholar 

  166. Coogan PF, Rosenberg L, Louik C, et al. NSAIDs and risk of colorectal cancer according to presence or absence of family history of the disease. Cancer Causes Control 2000; 11(3): 249–55

    Article  CAS  PubMed  Google Scholar 

  167. Langman MJ, Cheng KK, Gilman EA, et al. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 2000; 320(7250): 1642–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Muller AD, Sonnenberg A, Wasserman IH. Diseases preceding colon cancer: a case-control study among veterans. Dig Dis Sci 1994; 39(11): 2480–4

    Article  CAS  PubMed  Google Scholar 

  169. Bansal P, Sonnenberg A. Risk factors of colorectal cancer in inflammatory bowel disease. Am J Gastroenterol 1996; 91(1): 44–8

    CAS  PubMed  Google Scholar 

  170. Reeves MJ, Newcomb PA, Trentham-Dietz A, et al. Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 1996; 5(12): 955–60

    CAS  PubMed  Google Scholar 

  171. Rosenberg L, Louik C, Shapiro S. Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma. Cancer 1998; 82(12): 2326–33

    Article  CAS  PubMed  Google Scholar 

  172. Collet JP, Sharpe C, Belzile E, et al. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br J Cancer 1999; 81(1): 62–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum 1997; 40(9): 1580–6

    Article  CAS  PubMed  Google Scholar 

  174. Kauppi M, Pukkala E, Isomaki H. Low incidence of colorectal cancer in patients with rheumatoid arthritis. Clin Exp Rheumatol 1996; 14(5): 551–3

    CAS  PubMed  Google Scholar 

  175. Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study [abstract]. Epidemiology 1994; 5(2): 138–46

    Article  CAS  PubMed  Google Scholar 

  176. Paganini-Hill A. Aspirin and colorectal cancer [editorial]. BMJ 1993; 307(6899): 278–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Paganini-Hill A. Aspirin and the prevention of colorectal cancer: a review of the evidence. Semin Surg Oncol 1994; 10(3): 158–64

    Article  CAS  PubMed  Google Scholar 

  178. Paganini-Hill A, Chao A, Ross RK, et al. Aspirin use and chronic diseases: a cohort study of the elderly. BMJ 1989; 299(6710): 1247–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Paganini-Hill A, Hsu G, Ross RK, et al. Aspirin use and incidence of large-bowel cancer in a California retirement community [letter]. J Natl Cancer Inst 1991; 83(16): 1182–3

    Article  CAS  PubMed  Google Scholar 

  180. Paganini-Hill A, Hsu G, Ross RK, et al. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 1992; 326(19): 1290; discussion 1290–1

    CAS  PubMed  Google Scholar 

  181. Smalley W, Ray WA, Daugherty J, et al. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med 1999; 159(2): 161–6

    Article  CAS  PubMed  Google Scholar 

  182. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85(4): 307–11

    Article  CAS  PubMed  Google Scholar 

  183. Castelao JE, Yuan JM, Gago-Dominguez M, et al. Non-steroidal anti-inflammatory drugs and bladder cancer prevention. Br J Cancer 2000; 82(7): 1364–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Coogan PF, Rao SR, Rosenberg L, et al. The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer. Prev Med 1999; 29(2): 72–6

    Article  CAS  PubMed  Google Scholar 

  185. Egan KM, Stampfer MJ, Giovannucci E, et al. Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 1996; 88(14): 988–93

    Article  CAS  PubMed  Google Scholar 

  186. Harris RE, Kasbari S, Farrar WB. Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncol Rep 1999; 6(1): 71–3

    CAS  PubMed  Google Scholar 

  187. Harris RE, Namboodiri KK, Farrar WB. Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 1996; 7(2): 203–5

    Article  CAS  PubMed  Google Scholar 

  188. Sharpe CR, Collet JP, McNutt M, et al. Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer 2000; 83(1): 112–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Funkhouser EM, Sharp GB. Aspirin and reduced risk of esophageal carcinoma. Cancer 1995; 76(7): 1116–9

    Article  CAS  PubMed  Google Scholar 

  190. Farrow DC, Vaughan TL, Hansten PD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 1998; 7(2): 97–102

    CAS  PubMed  Google Scholar 

  191. Zaridze D, Borisova E, Maximovitch D, et al. Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia. Int J Cancer 1999; 82(4): 473–6

    Article  CAS  PubMed  Google Scholar 

  192. Nelson JE, Harris RE. Inverse association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs): results of a case-control study. Oncol Rep 2000; 7: 169–70

    CAS  PubMed  Google Scholar 

  193. Norrish AE, Jackson RT, McRae CU. Non-steroidal anti-inflammatory drugs and prostate cancer progression. Int J Cancer 1998 Aug 12; 77(4): 511–5

    Article  CAS  PubMed  Google Scholar 

  194. Kearney D, Crump C, Maynard C. Aspirin and NSAID-requiring conditions and the risk of esophageal carcinoma [abstract]. Gastroenterology 2002; 122: A71

    Article  Google Scholar 

  195. Harris RE, Beebe-Donk J, Namboodiri KK. Inverse association of non-steroidal anti-inflammatory drugs and malignant melanoma among women. Oncol Rep 2001; 8(3): 655–7

    CAS  PubMed  Google Scholar 

  196. Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). J Natl Cancer Inst 1998; 90(21): 1609–20

    Article  CAS  PubMed  Google Scholar 

  197. Smalley WE, DuBois RN. Colorectal cancer and nonsteroidal anti-inflammatory drugs. Adv Pharmacol 1997; 39: 1–20

    Article  CAS  PubMed  Google Scholar 

  198. Reddy BS, Rao CV, Scibert K. Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res 1996; 56(20): 4566–9

    CAS  PubMed  Google Scholar 

  199. Kawamori T, Rao CV, Scibert K, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998; 58(3): 409–12

    CAS  PubMed  Google Scholar 

  200. Reddy BS, Hirose Y, Lubet R, et al. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res 2000; 60(2): 293–7

    CAS  PubMed  Google Scholar 

  201. Jacoby RF, Scibert K, Cole CE, et al. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the Min mouse model of adenomatous polyposis. Cancer Res 2000; 60(18): 5040–4

    CAS  PubMed  Google Scholar 

  202. Sasai H, Masaki M, Wakitani K. Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522. Carcinogenesis 2000; 21(5): 953–8

    Article  CAS  PubMed  Google Scholar 

  203. Yoshimi N, Kawabata K, Hara A, et al. Inhibitory effect of NS-398, a selective cyclooxygenase-2 inhibitor, on azoxymethane-induced aberrant crypt foci in colon carcinogenesis of F344 rats. Jpn J Cancer Res 1997; 88(11): 1044–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Fukutake M, Nakatsugi S, Isoi T, et al. Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice. Carcinogenesis 1998; 19(11): 1939–42

    Article  CAS  PubMed  Google Scholar 

  205. Nakatsugi S, Fukutake M, Takahashi M, et al. Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice. Jpn J Cancer Res 1997; 88(12): 1117–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Yoshimi N, Shimizu M, Matsunaga K, et al. Chemopreventive effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, in rat colon carcinogenesis induced by azoxymethane. Jpn J Cancer Res 1999; 90(4): 406–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Oshima M, Murai N, Kargman S, et al. Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res 2001; 61(4): 1733–40

    CAS  PubMed  Google Scholar 

  208. Lai G, Ash C, Hay K, et al. Suppression of intestinal polyps in Msh2-deficient and non-Msh2-deficient multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Cancer Res 2001 Aug 15; 61(16): 6131–6

    Google Scholar 

  209. Harris RE, Alshafie GA, Abou-Issa H, et al. Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Cancer Res 2000; 60(8): 2101–3

    CAS  PubMed  Google Scholar 

  210. Matsunaga K, Yoshimi N, Yamada Y, et al. Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. Jpn J Cancer Res 1998 May; 89(5): 496–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Fischer SM, Lo HH, Gordon GB, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 1999; 25(4): 231–40

    Article  CAS  PubMed  Google Scholar 

  212. Pentland AP, Schoggins JW, Scott GA, et al. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999; 20(10): 1939–44

    Article  CAS  PubMed  Google Scholar 

  213. Muller-Decker K, Kopp-Schneider A, Marks F, et al. Localization of prostaglandin H synthase isoenzymes in murine epidermal tumors: suppression of skin tumor promotion by inhibition of prostaglandin H synthase-2. Mol Carcinog 1998; 23(1): 36–44

    Article  CAS  PubMed  Google Scholar 

  214. Grubbs CJ, Lubet RA, Koki AT, et al. Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res 2000; 60(20): 5599–602

    CAS  PubMed  Google Scholar 

  215. Okajima E, Denda A, Ozono S, et al. Chemopreventive effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on the development of rat urinary bladder carcinomas initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine. Cancer Res 1998; 58(14): 3028–31

    CAS  PubMed  Google Scholar 

  216. Li Z, Shimada Y, Kawabe A, et al. Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor. Carcinogenesis 2001 Apr; 22(4): 547–51

    Article  CAS  PubMed  Google Scholar 

  217. Rioux N, Castonguay A. Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res 1998; 58(23): 5354–60

    CAS  PubMed  Google Scholar 

  218. Shiotani H, Denda A, Yamamoto K, et al. Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-l-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res 2001 Feb 15; 61(4): 1451–6

    CAS  PubMed  Google Scholar 

  219. Torrance CJ, Jackson PE, Montgomery E, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000; 6(9): 1024–8

    Article  CAS  PubMed  Google Scholar 

  220. Sansom OJ, Stark LA, Dunlop MG, et al. Suppression of intestinal and mammary neoplasia by lifetime administration of aspirin in Apc(Min/+) and Apc(Min/+), Msh2(-/-) mice. Cancer Res 2001 Oct 1; 61(19): 7060–4

    CAS  PubMed  Google Scholar 

  221. Mahmoud NN, Boolbol SK, Dannenberg AJ, et al. The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis. Carcinogenesis 1998; 19(1): 87–91

    Article  CAS  PubMed  Google Scholar 

  222. Mahmoud NN, Dannenberg AJ, Mestre J, et al. Aspirin prevents tumors in a murine model of familial adenomatous polyposis. Surgery 1998; 124(2): 225–31

    Article  CAS  PubMed  Google Scholar 

  223. Boolbol SK, Dannenberg AJ, Chadburn A, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996; 56(11): 2556–60

    CAS  PubMed  Google Scholar 

  224. Hansen-Petrik MB, McEntee MF, Jull B, et al. Prostaglandin E2 protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in ApcMin/+ mice. Cancer Res 2002 Jan 1; 62(2): 403–8

    CAS  PubMed  Google Scholar 

  225. Wechter WJ, Murray Jr ED, Kantoci D, et al. Treatment and survival study in the C57BL/6J-APC(Min)/+(Min) mouse with R-flurbiprofen. Life Sci 2000 Jan 14; 66(8): 745–53

    Article  CAS  PubMed  Google Scholar 

  226. Robertson FM, Parrett ML, Joarder FS, et al. Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas. Cancer Lett 1998 Jan 9; 122(1–2): 165–75

    Article  CAS  PubMed  Google Scholar 

  227. Yao R, Rioux N, Castonguay A, et al. Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs’ chemopreventive efficacies in mouse lung tumorigenesis. Exp Lung Res 2000; 26(8): 731–42

    Article  PubMed  Google Scholar 

  228. Castonguay A, Rioux N, Duperron C, et al. Inhibition of lung tumorigenesis by NSAIDS: a working hypothesis. Exp Lung Res 1998; 24(4): 605–15

    Article  CAS  PubMed  Google Scholar 

  229. Hawk E, Lubet R, Limburg P. Chemoprevention in hereditary colorectal cancer syndromes. Cancer 1999; 86(11 Suppl.): 2551–63

    Article  CAS  PubMed  Google Scholar 

  230. Waddell WR, Loughry RW. Sulindac for polyposis of the colon. J Surg Oncol 1983; 24(1): 83–7

    Article  CAS  PubMed  Google Scholar 

  231. Chameau J, D’Aubigny N, Burtin P, et al. Rectal micropolyps after total colectomy in familial polyposis: efficacy of sulindac. Gastroenterol Clin Biol 1990; 14(2): 153–7

    Google Scholar 

  232. Friend WG. Sulindac suppression of colorectal polyps in Gardner’s syndrome. Am Fam Physician 1990 Mar; 41(3): 891–4

    CAS  PubMed  Google Scholar 

  233. Gonzaga RA, Lima FR, Carneiro S, et al. Sulindac treatment for familial polyposis coli [letter]. Lancet 1985 Mar 30; I(8431): 751

    Article  Google Scholar 

  234. Giardiello FM, Spannhake EW, DuBois RN, et al. Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis. Dig Dis Sci 1998; 43(2): 311–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Iwama T, Imajo M, Mishima Y. Is sulindac effective for familial adenomatous polyposis? Int J Colorectal Dis 1991; 6: 235

    Google Scholar 

  236. Muller A, Hurlimann R, Meyenberger C, et al. Sulindac in familial adenomatous polyposis coli-preliminary findings of a prospective study. Schweiz Med Wochenschr 1994; 124(15): 651–4

    CAS  PubMed  Google Scholar 

  237. Niv Y, Fraser GM. Adenocarcinoma in the rectal segment in familial polyposis coli is not prevented by sulindac therapy. Gastroenterology 1994; 107(3): 854–7

    Article  CAS  PubMed  Google Scholar 

  238. Rigau J, Pique JM, Rubio E, et al. Effects of long-term sulindac therapy on colonic polyposis. Ann Intern Med 1991 Dec 15; 115(12): 952–4

    Article  CAS  PubMed  Google Scholar 

  239. Spagnesi MT, Tonelli F, Dolara P, et al. Rectal proliferation and polyp occurrence in patients with familial adenomatous polyposis after sulindac treatment. Gastroenterology 1994; 106(2): 362–6

    Article  CAS  PubMed  Google Scholar 

  240. Tonelli F, Valanzano R, Dolara P. Sulindac therapy of colorectal polyps in familial adenomatous polyposis. Dig Dis 1994; 12(5): 259–64

    Article  CAS  PubMed  Google Scholar 

  241. Tonelli F, Valanzano R. Sulindac in familial adenomatous polyposis [letter]. Lancet 1993; 342(8879): 1120

    Article  CAS  PubMed  Google Scholar 

  242. Labayle D, Fischer D, Vielh P, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 1991; 101(3): 635–9

    Article  CAS  PubMed  Google Scholar 

  243. Nugent KP, Farmer KC, Spigelman AD, et al. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg 1993; 80(12): 1618–9

    Article  CAS  PubMed  Google Scholar 

  244. Giardiello FM, Hamilton SR, Krush AJ, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993; 328(18): 1313–6

    Article  CAS  PubMed  Google Scholar 

  245. Matsuhashi N, Nakajima A, Shinohara K, et al. Rectal cancer after sulindac therapy for a sporadic adenomatous colonic polyp. Am J Gastroenterol 1998 Nov; 93(11): 2261–6

    Article  CAS  PubMed  Google Scholar 

  246. Lynch HT, Thorson AG, Smyrk T. Rectal cancer after prolonged sulindac chemoprevention: a case report. Cancer 1995; 75(4): 936–8

    Article  CAS  PubMed  Google Scholar 

  247. Thorson AG, Lynch HT, Smyrk TC. Rectal cancer in FAP patient after sulindac [letter]. Lancet 1994; 343(8890): 180

    Article  CAS  PubMed  Google Scholar 

  248. Seow-Choen F, Vijayan V, Keng V. Prospective randomized study of sulindac versus calcium and calciferol for upper gastrointestinal polyps in familial adenomatous polyposis. Br J Surg 1996 Dec; 83(12): 1763–6

    Article  CAS  PubMed  Google Scholar 

  249. Richard CS, Berk T, Bapat BV, et al. Sulindac for periampullary polyps in FAP patients. Int J Colorectal Dis 1997; 12(1): 14–8

    Article  CAS  PubMed  Google Scholar 

  250. Parker AL, Kadakia SC, Maccini DM, et al. Disappearance of duodenal polyps in Gardner’s syndrome with sulindac therapy. Am J Gastroenterol 1993 Jan; 88(1): 93–4

    CAS  PubMed  Google Scholar 

  251. Debinski HS, Trojan J, Nugent KP, et al. Effect of sulindac on small polyps in familial adenomatous polyposis. Lancet 1995 Apr 1; 345(8953): 855–6

    Article  CAS  PubMed  Google Scholar 

  252. Waddell WR, Ganser GF, Cerise EJ, et al. Sulindac for polyposis of the colon. Am J Surg 1989; 157(1): 175–9

    Article  CAS  PubMed  Google Scholar 

  253. Winde G, Gumbinger HG, Osswald H, et al. The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration. Int J Colorectal Dis 1993; 8(1): 13–7

    Article  CAS  PubMed  Google Scholar 

  254. Winde G, Schmid KW, Brandt B, et al. Clinical and genomic influence of sulindac on rectal mucosa in familial adenomatous polyposis. Dis Colon Rectum 1997; 40(10): 1156–68; discussion 1168–9

    Article  CAS  PubMed  Google Scholar 

  255. Winde G, Schmid KW, Schlegel W, et al. Complete reversion and prevention of rectal adenomas in colectomized patients with familial adenomatous polyposis by rectal low-dose sulindac maintenance treatment: advantages of a low-dose nonsteroidal anti-inflammatory drug regimen in reversing adenomas exceeding 33 months. Dis Colon Rectum 1995; 38(8): 813–30

    Article  CAS  PubMed  Google Scholar 

  256. van Stolk R, Stoner G, Hayton WL, et al. Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis. Clin Cancer Res 2000; 6(1): 78–89

    PubMed  Google Scholar 

  257. Hirata K, Itoh H, Ohsato K. Regression of rectal polyps by indomethacin suppository in familial adenomatous polyposis: report of two cases. Dis Colon Rectum 1994; 37(9): 943–6

    Article  CAS  PubMed  Google Scholar 

  258. Hirota C, Iida M, Aoyagi K, et al. Effect of indomethacin suppositories on rectal polyposis in patients with familial adenomatous polyposis. Cancer 1996; 78(8): 1660–5

    Article  CAS  PubMed  Google Scholar 

  259. Dolara P, Caderni G, Tonelli F. Nimesulide, a selective anti-inflammatory cyclooxygenase-2 inhibitor, does not affect polyp number and mucosal proliferation in familial adenomatous polyposis [letter]. Scand J Gastroenterol 1999; 34(11): 1168

    Article  CAS  PubMed  Google Scholar 

  260. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000; 342(26): 1946–52

    Article  CAS  PubMed  Google Scholar 

  261. Phillips RK, Wallace MH, Lynch P, et al. A randomised, double-blind, placebo-controlled study of celecoxib, a selective cyclooxygenase-2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut. 2002; 50: 857–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Hixson LJ, Earnest DL, Fennerty MB, et al. NSAID effect on sporadic colon polyps. Am J Gastroenterol 1993; 88(10): 1652–6

    CAS  PubMed  Google Scholar 

  263. Matsuhashi N, Nakajima A, Fukushima Y, et al. Effects of sulindac on sporadic colorectal adenomatous polyps. Gut 1997; 40(3): 344–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Ladenheim J, Garcia G, Titzer D, et al. Effect of sulindac on sporadic colonic polyps. Gastroenterology 1995; 108(4): 1083–7

    Article  CAS  PubMed  Google Scholar 

  265. Gann PH, Manson JE, Glynn RJ, et al. Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 1993; 85(15): 1220–4

    Article  CAS  PubMed  Google Scholar 

  266. Carbone PP, Douglas JA, Larson PO, et al. Phase I chemoprevention study of piroxicam and alpha-difluoromethylornithine. Cancer Epidemiol Biomarkers Prev 1998 Oct; 7(10): 907–12

    CAS  PubMed  Google Scholar 

  267. Calaluce R, Earnest DL, Heddens D, et al. Effects of piroxicam on prostaglandin E2 levels in rectal mucosa of adenomatous polyp patients: a randomized phase IIb trial. Cancer Epidemiol Biomarkers Prev 2000 Dec; 9(12): 1287–92

    CAS  PubMed  Google Scholar 

  268. Chow HH, Earnest DL, Clark D, et al. Effect of subacute ibuprofen dosing on rectal mucosal prostaglandin E2 levels in healthy subjects with a history of resected polyps. Cancer Epidemiol Biomarkers Prev 2000 Apr; 9(4): 351–6

    CAS  PubMed  Google Scholar 

  269. Barnes CJ, Hamby-Mason RL, Hardman WE, et al. Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon. Cancer Epidemiol Biomarkers Prev 1999 Apr; 8 (4 Pt 1): 311–5

    CAS  PubMed  Google Scholar 

  270. Ruffin IV MT, Krishnan K, Rock CL, et al. Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose. J Natl Cancer Inst 1997 Aug 6; 89(15): 1152–60

    Article  CAS  PubMed  Google Scholar 

  271. Baron JA, Cole BF, Mott LA, et al. Aspirin chemoprevention of colorectal adenomas [abstract]. Proc AACR 2002 Mar; 43: 669

    Google Scholar 

  272. Benamouzig R, Deyra J, Martin A, et al. Efficacy of lysin acetylsalicylate to prevent colorectal adenomas: one year results of the APACC Randomized Trial [abstract]. Gastroenterology 2002; 122: A70

    Google Scholar 

  273. Ding XZ, Tong WG, Adrian TE. Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Anticancer Res 2000; 20(4): 2625–31

    CAS  PubMed  Google Scholar 

  274. Hara A, Yoshimi N, Niwa M, et al. Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines. Jpn J Cancer Res 1997 Jun; 88(6): 600–4

    Article  CAS  PubMed  Google Scholar 

  275. Sawaoka H, Kawano S, Tsuji S, et al. Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. Am J Physiol 1998; 274 (6 Pt 1): G1061–7

    CAS  PubMed  Google Scholar 

  276. Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 2000; 275(15): 11397–403

    Article  CAS  PubMed  Google Scholar 

  277. Liu XH, Yao S, Kirschenbaum A, et al. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res 1998; 58(19): 4245–9

    CAS  PubMed  Google Scholar 

  278. Nishimura G, Yanoma S, Mizuno H, et al. A selective cyclooxygenase-2 inhibitor suppresses tumor growth in nude mouse xenografted with human head and neck squamous carcinoma cells. Jpn J Cancer Res 1999; 90(10): 1152–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  279. Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000; 60(5): 1306–11

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  281. Sharma RA, Gescher A, Plastaras JP, et al. Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells. Carcinogenesis 2001 Sep; 22(9): 1557–60

    Article  CAS  PubMed  Google Scholar 

  282. McDougall CJ, Ngoi SS, Goldman IS, et al. Reduced expression of HLA class I and II antigens in colon cancer. Cancer Res 1990 Dec 15; 50(24): 8023–7

    CAS  PubMed  Google Scholar 

  283. Wilgus TA, Ross MS, Parrett ML, et al. Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation. Prostaglandins Other Lipid Mediat 2000 Oct; 62(4): 367–84

    Article  CAS  PubMed  Google Scholar 

  284. Zhang X, Morham SG, Langenbach R, et al. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med 1999; 190(4): 451–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Zhang L, Yu J, Park BH, et al. Role of BAX in the apoptotic response to anticancer agents. Science 2000; 290(5493): 989–92

    Article  CAS  PubMed  Google Scholar 

  286. Kopelovich L, Fay JR, Glazer RI, et al. Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. Molec Cancer Ther. 2002; 1: 357–363

    CAS  Google Scholar 

  287. He TC, Chan TA, Vogelstein B, et al. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 1999; 99(3): 335–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Park BH, Vogelstein B, Kanzler KW. Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci USA 2001 Feb 27; 98(5): 2598–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  289. Yamamoto Y, Yin MJ, Lin KM, et al. Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 1999 Sep 17; 274(38): 27307–14

    Article  CAS  PubMed  Google Scholar 

  290. Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998 Nov 5; 396(6706): 77–80

    Article  CAS  PubMed  Google Scholar 

  291. Goppelt-Struebe M. Molecular mechanisms involved in the regulation of prosta-glandin biosynthesis by glucocorticoids. Biochem Pharmacol 1997 May 15; 53(10): 1389–95

    Article  CAS  PubMed  Google Scholar 

  292. Petrik MB, McEntee MF, Chiu CH, et al. Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice. J Nutr 2000 May; 130(5): 1153–8

    Article  CAS  PubMed  Google Scholar 

  293. Rao CV, Simi B, Wynn TT, et al. Modulating effect of amount and types of dietary fat on colonic mucosal phospholipase A2, phosphatidylinositol-specific phos-pholipase C activities, and cyclooxygenase metabolite formation during different stages of colon tumor promotion in male F344 rats. Cancer Res 1996 Feb 1; 56(3): 532–7

    CAS  PubMed  Google Scholar 

  294. Rao CV, Hirose Y, Indranie C, et al. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res 2001 Mar 1; 61(5): 1927–33

    CAS  PubMed  Google Scholar 

  295. Hong KH, Bonventre JC, O’Leary E, et al. Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis. Proc Natl Acad Sci USA 2001 Mar 27; 98(7): 3935–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  296. Takaku K, Sonoshita M, Sasaki N, et al. Suppression of intestinal polyposis in Apc(delta 716) knockout mice by an additional mutation in the cytosolic phospholipase A(2) gene. J Biol Chem 2000; 275(44): 34013–6

    Article  CAS  PubMed  Google Scholar 

  297. Moser AR, Dove WF, Roth KA, et al. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J Cell Biol 1992 Mar; 116(6): 1517–26

    Article  CAS  PubMed  Google Scholar 

  298. Cormier RT, Hong KH, Halberg RB, et al. Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Nat Genet 1997 Sep; 17(1): 88–91

    Article  CAS  PubMed  Google Scholar 

  299. Sonoshita M, Takaku K, Sasaki N, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med 2001; 7(9): 1048–51

    Article  CAS  PubMed  Google Scholar 

  300. Seno H, Oshima M, Ishikawa TO, et al. Cyclooxygenase 2- and Prostaglandin E(2) Receptor EP(2)-dependent Angiogenesis in Apc(Delta716) Mouse Intestinal Polyps. Cancer Res 2002 Jan 15; 62(2): 506–11

    CAS  PubMed  Google Scholar 

  301. Jabbour HN, Milne SA, Williams AR, et al. Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. Br J Cancer 2001 Sep; 85(7): 1023–31

    Article  CAS  PubMed  Google Scholar 

  302. Sheng H, Shao J, Washington MK, et al. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001 May 25; 276(21): 18075–81

    Article  CAS  PubMed  Google Scholar 

  303. Watanabe K, Kawamori T, Nakatsugi S, et al. Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res 1999 Oct 15; 59(20): 5093–6

    CAS  PubMed  Google Scholar 

  304. Watanabe K, Kawamori T, Nakatsugi S, et al. Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice. Cancer Lett 2000; 156(1): 57–61

    Article  CAS  PubMed  Google Scholar 

  305. Giardiello FM, Hamilton SR, Hylind LM, et al. Ornithine decarboxylase and polyamines in familial adenomatous polyposis. Cancer Res 1997 Jan 15; 57(2): 199–201

    CAS  PubMed  Google Scholar 

  306. Patchett SE, Alstead EM, Trzeciak L, et al. Rectal mucosal ornithine decarboxylase activity in familial adenomatous polyposis after ileorectal anastomosis. Gut 1994 Nov; 35(11): 1624–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  307. Khan KN, Masferrer JL, Woerner BM, et al. Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon. Scand J Gastroenterol 2001 Aug; 36(8): 865–9

    Article  CAS  PubMed  Google Scholar 

  308. Humar B, D’Orazio D, Albrecht C, et al. Expression of putative anticancer targets in familial adenomatous polyposis and its association with the APC mutation status. Int J Oncol 2001 Dec; 19(6): 1179–86

    CAS  PubMed  Google Scholar 

  309. Katdare M, Kopelovich L, Telang N. Chemopreventive agents inhibit aberrant proliferation of the aneuploid phenotype in a colon epithelial cell line established from Apc 1638N [+/-] mouse. Ann N Y Acad Sci 2001 Dec; 952: 169–74

    Article  CAS  PubMed  Google Scholar 

  310. Nigro ND, Bull AW, Boyd ME. Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil. J Natl Cancer Inst 1986 Dec; 77(6): 1309–13

    CAS  PubMed  Google Scholar 

  311. Jacoby RF, Cole CE, Tutsch K, et al. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer Res 2000 Apr 1; 60(7): 1864–70

    CAS  PubMed  Google Scholar 

  312. Li H, Schut HA, Conran P, et al. Prevention by aspirin and its combination with alpha-difluoromethylornithine of azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E2 levels in rat colon. Carcinogenesis 1999 Mar; 20(3): 425–30

    Article  CAS  PubMed  Google Scholar 

  313. Rao CV, Tokumo K, Rigotty J, et al. Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, alpha-difluoromethylornithine, 16 alpha-fluoro-5-androsten-17-one, and ellagic acid individually and in combination. Cancer Res 1991 Sep 1; 51(17): 4528–34

    CAS  PubMed  Google Scholar 

  314. Reddy BS, Nayini J, Tokumo K, et al. Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. Cancer Res 1990 May 1; 50(9): 2562–8

    CAS  PubMed  Google Scholar 

  315. Rivers JK, McLean DI. An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses. Arch Dermatol 1997 Oct; 133(10): 1239–42

    Article  CAS  PubMed  Google Scholar 

  316. Jenkins CA, Bruera E. Nonsteroidal anti-inflammatory drugs as adjuvant analgesics in cancer patients. Palliat Med 1999; 13(3): 183–96

    Article  CAS  PubMed  Google Scholar 

  317. Yalcin S, Altundag K, Asil M, et al. Sublingual piroxicam for cancer pain. Med Oncol 1998; 15(2): 137–9

    Article  CAS  PubMed  Google Scholar 

  318. Mercadante S. The use of anti-inflammatory drugs in cancer pain. Cancer Treat Rev 2001; 27(1): 51–61

    Article  CAS  PubMed  Google Scholar 

  319. McDonnell FJ, Sloan JW, Hamann SR. Advances in cancer pain management. Curr Oncol Rep 2000 Jul; 2(4): 351–7

    Article  CAS  PubMed  Google Scholar 

  320. Lundholm K, Gelin J, Hyltander A, et al. Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 1994; 54(21): 5602–6

    CAS  PubMed  Google Scholar 

  321. Alshafie GA, Abou-Issa HM, Scibert K, et al. Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model. Oncol Rep 2000 Nov; 7(6): 1377–81

    CAS  PubMed  Google Scholar 

  322. Duffy CP, Elliott CJ, O’Connor RA, et al. Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of non-steroidal anti-inflammatory drugs (NSAIDs). Eur J Cancer 1998 Jul; 34(8): 1250–9

    Article  CAS  PubMed  Google Scholar 

  323. Goluboff ET, Shabsigh A, Saidi JA, et al. Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Urology 1999 Feb; 53(2): 440–5

    Article  CAS  PubMed  Google Scholar 

  324. Jiang MC, Liao CF, Lee PH. Aspirin inhibits matrix metalloproteinase-2 activity, increases E-cadherin production, and inhibits in vitro invasion of tumor cells. Biochem Biophys Res Commun 2001 Apr 6; 282(3): 671–7

    Article  CAS  PubMed  Google Scholar 

  325. Knapp DW, Glickman NW, Widmer WR, et al. Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 2000; 46(3): 221–6

    Article  CAS  PubMed  Google Scholar 

  326. Rozic JG, Chakraborty C, Lala PK. Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis. Int J Cancer 2001 Aug 15; 93(4): 497–506

    Article  CAS  PubMed  Google Scholar 

  327. Petersen C, Petersen S, Milas L, et al. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 2000 Jun; 6(6): 2513–20

    CAS  PubMed  Google Scholar 

  328. Tsubouchi Y, Mukai S, Kawahito Y, et al. Meloxicam inhibits the growth of non-small cell lung cancer. Anticancer Res 2000 Sep; 20(5A): 2867–72

    CAS  PubMed  Google Scholar 

  329. Pyo H, Choy H, Amorino GP, et al. A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res 2001 Oct; 7(10): 2998–3005

    CAS  PubMed  Google Scholar 

  330. Kobayashi S, Okada S, Hasumi T, et al. The marked anticancer effect of combined VCR, MTX, and indomethacin against drug-resistant recurrent small cell lung carcinoma after conventional chemotherapy: report of a case. Surg Today 1999; 29(7): 666–9

    Article  CAS  PubMed  Google Scholar 

  331. Yoshinaga K, Teramura M, Iwabe K, et al. Anti-lymphoma effect of naproxen and indomethacin in a patient with relapsed diffuse large B-cell lymphoma. Am J Hematol 2001 Mar; 66(3): 220–3

    Article  CAS  PubMed  Google Scholar 

  332. Anderson WF, Umar A, Viner JL, et al. Potential role of NSAIDs and COX-2 blockade in cancer therapy. In: Harris RE, editor. Cyclooxygenase 2 (COX-2) blockade in cancer prevention and therapy. Totowa (NJ): The Humana Press Inc, 2002. 313–340

    Chapter  Google Scholar 

  333. Mann M, Sheng H, Shao J, et al. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 2001 Jun; 120(7): 1713–9

    Article  CAS  PubMed  Google Scholar 

  334. Yip-Schneider MT, Sweeney CJ, Jung SH, et al. Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells. J Pharmacol Exp Ther 2001 Sep; 298(3): 976–85

    CAS  PubMed  Google Scholar 

  335. Roller A, Bahr OR, Streffer J, et al. Selective potentiation of drug cytotoxicity by NSAID in human glioma cells: the role of COX-1 and MRP. Biochem Biophys Res Commun 1999 Jun 16; 259(3): 600–5

    Article  CAS  PubMed  Google Scholar 

  336. Milas L, Kishi K, Hunter N, et al. Enhancement of tumor response to gamma-radiation by an inhibitor of cyclooxygenase-2 enzyme. J Natl Cancer Inst 1999 Sep 1; 91(17): 1501–4

    Article  CAS  PubMed  Google Scholar 

  337. Palayoor ST, Bump EA, Calderwood SK, et al. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res 1998 Mar; 4(3): 763–71

    CAS  PubMed  Google Scholar 

  338. Dicker AP, Williams TL, Grant DS. Targeting angiogenic processes by combination rofecoxib and ionizing radiation. Am J Clin Oncol 2001 Oct; 24(5): 438–42

    Article  CAS  PubMed  Google Scholar 

  339. Williams CS, Watson AJ, Sheng H, et al. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res 2000 Nov 1; 60(21): 6045–51

    CAS  PubMed  Google Scholar 

  340. Goldman AP, Williams CS, Sheng H, et al. Meloxicam inhibits the growth of colorectal cancer cells. Carcinogenesis 1998 Dec; 19(12): 2195–9

    Article  CAS  PubMed  Google Scholar 

  341. Sheng H, Shao J, Kirkland SC, et al. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997 May 1; 99(9): 2254–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  342. Chiu CH, McEntee MF, Whelan J. Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis. Cancer Res 1997; 57(19): 4267–73

    CAS  PubMed  Google Scholar 

  343. Wechter WJ, Leipold DD, Murray Jr ED, et al. E-7869 (R-flurbiprofen) inhibits progression of prostate cancer in the TRAMP mouse. Cancer Res 2000 Apr 15; 60(8): 2203–8

    CAS  PubMed  Google Scholar 

  344. Mcikova-Kalicka K, Bojkova B, Adamekova E, et al. Preventive effect of indomethacin and melatonin on 7, 12-dimethybenz/a/anthracene-induced mammary carcinogenesis in female Sprague-Dawley rats: a preliminary report. Folia Biol (Praha) 2001; 47(2): 75–9

    CAS  Google Scholar 

  345. Creagan ET, Buckner JC, Hahn RG, et al. An evaluation of recombinant leukocyte A interferon with aspirin in patients with metastatic renal cell cancer. Cancer 1988; 61(9): 1787–91

    Article  CAS  PubMed  Google Scholar 

  346. Creagan ET, Twito DI, Johansson SL, et al. A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. J Clin Oncol 1991; 9(12): 2104–9

    Article  CAS  PubMed  Google Scholar 

  347. Mertens WC, Bramwell VH, Banerjee D, et al. Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma. Cancer Biother 1993; 8(3): 229–33

    Article  CAS  PubMed  Google Scholar 

  348. Mertens WC, Bramwell VH, Gwadry-Sridhar F, et al. Effect of indomethacin plus ranitidine in advanced melanoma patients on high-dose interleukin-2. Lancet 1992 Aug 15; 340(8816): 397–8

    Article  CAS  PubMed  Google Scholar 

  349. Mertens WC, Bramwell VH, Banerjee D, et al. Sustained indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced malignant melanoma: a phase II study. Clin Oncol (R Coll Radiol) 1993; 5(2): 107–13

    Article  CAS  Google Scholar 

  350. Mertens WC, Lohmann RC. Oral indomethacin and ranitidine in advanced melanoma: a phase II study. Clin Oncol (R Coll Radiol) 1996; 8(2): 112–5

    Article  CAS  Google Scholar 

  351. Miller RL, Steis RG, Clark JW, et al. Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Res 1989 Apr 1; 49(7): 1871–6

    CAS  PubMed  Google Scholar 

  352. Janik JE, Miller LL, Longo DL, et al. Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma. J Natl Cancer Inst 1996 Jan 3; 88(1): 44–9

    Article  CAS  PubMed  Google Scholar 

  353. Pillsbury III HC, Webster WP, Rosenman J. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers. Arch Otolaryngol Head Neck Surg 1986 May; 112(5): 552–3

    Article  PubMed  Google Scholar 

  354. Cross DS, Platt JL, Juhn SK, et al. Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1992 May; 118(5): 526–8

    Article  CAS  PubMed  Google Scholar 

  355. Sosman JA, Kohler PC, Hank JA, et al. Repetitive weekly cycles of interleukin-2, II: clinical and immunologic effects of dose, schedule, and addition of indomethacin. J Natl Cancer Inst 1988; 80(18): 1451–61

    Article  CAS  PubMed  Google Scholar 

  356. Braun DP, Bonomi PD, Taylor IV SG, et al. Modification of the effects of cytotoxic chemotherapy on the immune responses of cancer patients with a nonsteroidal, antiinflammatory drug, piroxicam: a pilot study of the Eastern Cooperative Oncology Group. J Biol Response Mod 1987; 6(3): 331–45

    CAS  PubMed  Google Scholar 

  357. Sinicrope FA, Pazdur R, Levin B. Phase I trial of sulindac plus 5-fluorouracil and levamisole: potential adjuvant therapy for colon carcinoma. Clin Cancer Res 1996 Jan; 2(1): 37–41

    CAS  PubMed  Google Scholar 

  358. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340(24): 1888–99

    Article  CAS  PubMed  Google Scholar 

  359. Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med 1998; 105(1 Suppl. 2): 31S–8S

    Article  CAS  PubMed  Google Scholar 

  360. Larkai EN, Smith JL, Lidsky MD, et al. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol 1987 Nov; 82(11): 1153–8

    CAS  PubMed  Google Scholar 

  361. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999 Apr; 26Suppl. 56: 18–24

    Google Scholar 

  362. Bjorkman DJ. Current status of nonsteroidal anti-inflammatory drug (NSAID) use in the United States: risk factors and frequency of complications. Am J Med 1999 Dec 13; 107(6A): 3S–8S; discussion 8S–10S

    Article  CAS  PubMed  Google Scholar 

  363. Whelton A, Maurath CJ, Verburg KM, et al. Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. Am J Ther 2000 May; 7(3): 159–75

    Article  CAS  PubMed  Google Scholar 

  364. Schafer AI. Effects of nonsteroidal anti-inflammatory therapy on platelets. Am J Med 1999 May 31; 106(5B): 25S–36S

    Article  CAS  PubMed  Google Scholar 

  365. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345(6): 433–42

    Article  CAS  PubMed  Google Scholar 

  366. Prescott SM. Is cyclooxygenase-2 the alpha and the omega in cancer? J Clin Invest 2000; 105(11): 1511–3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  367. Mizuno H, Sakamoto C, Matsuda K, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 1997 Feb; 112(2): 387–97

    Article  CAS  PubMed  Google Scholar 

  368. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR Study Group. N Engl J Med 2000; 343(21): 1520–8

    Article  CAS  PubMed  Google Scholar 

  369. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis, the CLASS study, a randomized controlled trial: Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284(10): 1247–55

    Article  CAS  PubMed  Google Scholar 

  370. Langman MJ, Jensen DM, Watson DJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999 Nov 24; 282(20): 1929–33

    Article  CAS  PubMed  Google Scholar 

  371. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001 Aug; 286(8): 954–9

    Article  CAS  PubMed  Google Scholar 

  372. Sanmuganathan PS, Ghahramani P, Jackson PR, et al. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart 2001 Mar; 85(3): 265–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  373. Merck COX-2 cardiovascular safety studies will enroll 30,000 subjects ‘The Pink Sheet’. Chevy Chase (MD): F-D-C Reports, Inc, 2001: 12

  374. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000 May; 35(5): 937–40

    Article  CAS  PubMed  Google Scholar 

  375. Rocha JL, Fernandez-Alonso J. Acute tubulointerstitial nephritis associated with the selective COX-2 enzyme inhibitor, rofecoxib. Lancet 2001 Jun 16; 357(9272): 1946–7

    Article  CAS  PubMed  Google Scholar 

  376. Dinchuk JE, Car BD, Focht RJ, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 1995 Nov 23; 378(6555): 406–9

    Article  CAS  PubMed  Google Scholar 

  377. Komhoff M, Wang JL, Cheng HF, et al. Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and renal cortical development. Kidney Int 2000 Feb; 57(2): 414–22

    Article  CAS  PubMed  Google Scholar 

  378. Mersfelder TL, Stewart LR. Warfarin and celecoxib interaction. Ann Pharmacother 2000 Mar; 34(3): 325–7

    Article  CAS  PubMed  Google Scholar 

  379. Haase KK, Rojas-Fernandez CH, Lane L, et al. Potential interaction between celecoxib and warfarin. Ann Pharmacother 2000 May; 34(5): 666–7

    Article  CAS  PubMed  Google Scholar 

  380. Santini G, Patrignani P, Sciulli MG, et al. The human pharmacology of monocyte cyclooxygenase 2 inhibition by Cortisol and synthetic glucocorticoids. Clin Pharmacol Ther 2001 Nov; 70(5): 475–83

    Article  CAS  PubMed  Google Scholar 

  381. Rao CV, Indranie C, Simi B, et al. Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooygenase-2 inhibitors. Cancer Res 2001; 62: 165–70

    Google Scholar 

  382. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995 Aug 15; 123(4): 241–9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ernest T. Hawk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hawk, E.T., Viner, J.L., Umax, A. et al. Cancer and the Cyclo-Oxygenase Enzyme. Am J Cancer 2, 27–55 (2003). https://doi.org/10.2165/00024669-200302010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00024669-200302010-00003

Keywords

Navigation