The Role of Cyclooxygenase-2 Inhibitors in Combined Modality Therapy

  • Hong Pyo
  • Raymond N. DuBois
  • Hak Choy
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Since the German chemist, Felix Hoffman, first developed a molecule with analgesic activity called acetylsalicylic acid or aspirin for his employer, the Bayer Company, in 1893, a class of drugs referred to as nonsteroidal antiinflammatory drugs (NSAIDs) has evolved that are now, 100 years later, among the most widely used therapeutic agents known to mankind (1). In 1988, Kune et al. found an inverse association between aspirin use and the risk for colorectal cancer (2). This unexpected finding occurred in the context of a case-control study that explored numerous potential associations with colorectal cancer risk. Although the authors speculated that this inverse association could be causal, general interest appeared to be limited until other studies reported similar findings in 1991 (3,4).


Colorectal Cancer Familial Adenomatous Polyposis Adenomatous Polyposis Coli Colorectal Cancer Risk Adenomatous Polyposis Coli Gene 
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  1. 1.
    DuBois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063–1073.Google Scholar
  2. 2.
    Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illness, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988; 48: 4399–4404.PubMedGoogle Scholar
  3. 3.
    Rosenberg L, Palmer J, Zauber A, et al. A hypothesis: non-steroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 1991; 83: 355–358.PubMedCrossRefGoogle Scholar
  4. 4.
    Thun MJ, Namboodiri MM, Heath CW Jr, et al. Aspirin use and reduced risk of fatal colon cancer. New Engl J Med 1991; 325: 1593–1596.PubMedCrossRefGoogle Scholar
  5. 5.
    Giovannucci E. The prevention of colorectal cancer by aspirin use. Biomed Pharmacother 1999; 53: 303–308.PubMedCrossRefGoogle Scholar
  6. 6.
    Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999; 18: 7908–7916.PubMedCrossRefGoogle Scholar
  7. 7.
    Masferrer JL, Isakson PC, Seibert K. Cyclooxygenase-2 inhibitors. A new class of anti-inflammatory agents that spare the gastrointestinal tract. Gastroenterol Clin North Am 1996; 25: 363–372.PubMedCrossRefGoogle Scholar
  8. 8.
    Williams C, Shattuck-Brandt RL, DuBois RN. The role of COX-2 in intestinal cancer. Ann NYAcad Sci 1999; 889: 72–83.CrossRefGoogle Scholar
  9. 9.
    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: 4926–4931.PubMedGoogle Scholar
  10. 10.
    Deininger MH, Weller M, Streffer J, et al. Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo. Acta Neuropathol 1999; 98: 240–244.PubMedCrossRefGoogle Scholar
  11. 11.
    Mestre JR, Chan G, Zhang F, et al. Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer. Ann NY Acad Sci 1999; 889: 62–71.PubMedCrossRefGoogle Scholar
  12. 12.
    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: 991–994.PubMedGoogle Scholar
  13. 13.
    Zimmermann KC, Sarbia M, Weber AA, et al. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 1999; 59: 198–204.PubMedGoogle Scholar
  14. 14.
    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: 2929–2934.PubMedGoogle Scholar
  15. 15.
    Shamma A, Yamamoto H, Doki Y, et al. Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. Clin Cancer Res 2000; 6: 1229–1238.PubMedGoogle Scholar
  16. 16.
    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: 171–174.PubMedGoogle Scholar
  17. 17.
    Marrogi AJ, Travis WD, Welsh JA, et al. Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma. Clin Cancer Res 2000; 6: 4739–4744.PubMedGoogle Scholar
  18. 18.
    Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 2000; 89: 2637–2645.PubMedCrossRefGoogle Scholar
  19. 19.
    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: 73–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Achiwa H, Yatabe Y, Hida T, et al. Prognostic significance of elevated cyclooxygenase-2 expression in primary, resected lung adenocarcinoma. Clin Cancer Res 1999; 5: 1001–1005.PubMedGoogle Scholar
  21. 21.
    Wolff H, Saukkonen K, Anttila S, et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 1998; 58: 4997–5001.PubMedGoogle Scholar
  22. 22.
    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: 3761–3764.PubMedGoogle Scholar
  23. 23.
    Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase2 inhibitors. Cancer Res 2000; 60: 1306–1311.PubMedGoogle Scholar
  24. 24.
    Brueggemeier RW, Quinn AL, Parrett ML, et al. Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 1999; 140: 27–35.PubMedCrossRefGoogle Scholar
  25. 25.
    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: 965–968.PubMedGoogle Scholar
  26. 26.
    Uefuji K, Ichikura T, Mochizuki H, et al. Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol 1998; 69: 168–172.PubMedCrossRefGoogle Scholar
  27. 27.
    Lim HY, Joo HJ, Choi JH, et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 2000; 6: 519–525.PubMedGoogle Scholar
  28. 28.
    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: 4005–4012.PubMedGoogle Scholar
  29. 29.
    Shiota G, Okubo M, Noumi T, et al. Cyclooxygenase-2 expression in hepatocellular carcinoma. Hepatogastroenterology 1999; 46: 407–412.PubMedGoogle Scholar
  30. 30.
    Koshiba T, Hosotani R. Miyamoto Y, et al. Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors. Ira J Pancreatol 1999; 26: 69–76.CrossRefGoogle Scholar
  31. 31.
    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: 4356–4362.PubMedGoogle Scholar
  32. 32.
    Okami J, Yamamoto H, Fujiwara Y, et al. Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin Cancer Res 1999; 5: 2018–2024.PubMedGoogle Scholar
  33. 33.
    Tucker ON, Dannenberg AJ, Yang EK, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999; 59: 987–990.PubMedGoogle Scholar
  34. 34.
    Dimberg J, Samuelsson A, Hugander A, et al. Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut 1999; 45: 730–732.PubMedCrossRefGoogle Scholar
  35. 35.
    Sheehan KM, Sheahan K, O’Donoghue DP, et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 1999; 282: 1254–1257.PubMedCrossRefGoogle Scholar
  36. 36.
    Eberhart CE, Coffey RI, Radhika A, et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107: 1183–1188.PubMedGoogle Scholar
  37. 37.
    Sano H, Kawahito Y, Wilder RL, et al. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 1995; 55: 3785–3789.PubMedGoogle Scholar
  38. 38.
    Shirahama T. Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. Clin Cancer Res 2000; 6: 2424–2430.PubMedGoogle Scholar
  39. 39.
    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; 15: 5647–5650.Google Scholar
  40. 40.
    Kirschenbaum A, Klauner AP, Lee R, et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate. Urology 2000; 56: 671–676.PubMedCrossRefGoogle Scholar
  41. 41.
    Gupta S, Srivastava M, Ahmad N, et al. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 2000; 42: 73–78.PubMedCrossRefGoogle Scholar
  42. 42.
    Kargman S, Charleson S, Cartwright M, et al. Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts. Gastroenterology 1996; 111: 445–454.PubMedCrossRefGoogle Scholar
  43. 43.
    Thun MJ. Aspirin and gastrointestinal cancer. Adv Exp Med Biol 1997; 400A: 395–402.CrossRefGoogle Scholar
  44. 44.
    Thun MJ. NSAID use and decreased risk of gastrointestinal cancers. Gastroenterol Clin North Am 1996; 25: 333–348.PubMedCrossRefGoogle Scholar
  45. 45.
    Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. New Engl J Med 1995; 333: 609–614.PubMedCrossRefGoogle Scholar
  46. 46.
    Vainio H, Morgan G, Kleihues P. An international evaluation of the cancer-preventive potential of non-steroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prey 1997; 6: 749–753.Google Scholar
  47. 47.
    Miyaki M, Konishi M, Kikuchi-Yanoshita R, et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res 1994; 54: 3011–3020.PubMedGoogle Scholar
  48. 48.
    Powell SM, Zilz N, Beazer-Barclay Y, et al. APC mutations occur early during colorectal tumorigenesis. Nature 1992; 359: 235–237.PubMedCrossRefGoogle Scholar
  49. 49.
    Ahnen DJ. Colon cancer prevention by NSAIDs: what is the mechanism of action? Eur J Surg Suppl 1998; 582: 111–114.PubMedGoogle Scholar
  50. 50.
    Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New Engl J Med 2000; 342: 1946–1952.PubMedCrossRefGoogle Scholar
  51. 51.
    Williams CS, Smalley W, DuBois RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest 1997; 100: 1325–1329.PubMedCrossRefGoogle Scholar
  52. 52.
    Jacoby RF, Seibert 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: 5040–5044.PubMedGoogle Scholar
  53. 53.
    Kawamori T, Rao CV, Seibert K, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998; 58: 409–412.PubMedGoogle Scholar
  54. 54.
    Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in APCΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87: 803–809.PubMedCrossRefGoogle Scholar
  55. 55.
    Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995; 83: 493–501.PubMedCrossRefGoogle Scholar
  56. 56.
    Tsujii M, Kawano S, Tsujii S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998; 93: 705–716.PubMedCrossRefGoogle Scholar
  57. 57.
    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: 4064–4068.PubMedGoogle Scholar
  58. 58.
    Tomozawa S, Tsuno NH, Sunami E, et al. Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastases, of colorectal cancer. BrJ Cancer 2000; 83: 324–328.CrossRefGoogle Scholar
  59. 59.
    Sheehan KM, Sheahan K, O’Donoghue DP, et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 1999; 282: 1254–1257.PubMedCrossRefGoogle Scholar
  60. 60.
    Karmali RA. Eicosanoids in neoplasia. Prey Med 1987; 16: 493–502.CrossRefGoogle Scholar
  61. 61.
    Zhang S, Fulton AM. Modulation of integrin-laminin receptor function on mammary tumor cells by prostaglandin E2 receptor antagonism. Cancer Lett 1994; 85: 233–238.PubMedCrossRefGoogle Scholar
  62. 62.
    Qiao L, Kozoni V, Tsioulias GJ, et al. Selected eicosanoids increase the proliferation rate of human colon carcinoma cell lines and mouse colonocytes in vivo. Biochem Biophys Acta 1995; 1258: 215–223.PubMedCrossRefGoogle Scholar
  63. 63.
    Bortuzzo C, Hanif R, Kashfi K, et al. The effect of leukotrienes B and selected HETEs on the proliferation of colon cancer cells. Biochem Biophys Acta 1996; 1300: 240–246.PubMedCrossRefGoogle Scholar
  64. 64.
    Gupta RA, DuBois RN. Aspirin, NSAID, and colon cancer prevention: mechanisms? Gastroenterology 1998; 114: 1095–1100.PubMedCrossRefGoogle Scholar
  65. 65.
    Crew TE, Elder DJE, Paraskeva CA. Cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug enhances the growth inhibitory effect of butyrate in colorectal carcinoma cells expressing COX-2 protein: regulation of COX-2 by butyrate. Carcinogenesis 2000; 21: 69–77.PubMedCrossRefGoogle Scholar
  66. 66.
    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 Bc1–2. J Biol Chem 2000; 275:11, 397–11, 403.Google Scholar
  67. 67.
    Liu XH, Yao S, Kirschenbaum A, et al. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates Bc1–2 expression in LNCaP cells. Cancer Res 1998; 58: 4245–4249.PubMedGoogle Scholar
  68. 68.
    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; 88: 600–604.PubMedCrossRefGoogle Scholar
  69. 69.
    Sheng H, Shao J, Morrow JD, et al. Modulation of apoptosis and Bc1–2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 1998; 58: 362–366.PubMedGoogle Scholar
  70. 70.
    Elder DJE, Halton DE, Hague A, et al. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. Clin Cancer Res 1997; 3: 1679–1683.PubMedGoogle Scholar
  71. 71.
    Hsueh CT, Chiu CF, Kelsen DP, et al. Selective inhibition of cyclooxygenase-2 enhances mitomycinC-induced apoptosis. Cancer Chemother Pharmacol 2000; 45: 389–396.PubMedCrossRefGoogle Scholar
  72. 72.
    Goldberg Y, Nassif II, Pittas A, et al. The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells: alterations in tumor suppressor and cell cycle-regulatory proteins. Oncogene 1996; 12: 893–901.PubMedGoogle Scholar
  73. 73.
    Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 1995; 55: 3110–3116.PubMedGoogle Scholar
  74. 74.
    Piazza GA, Rahm AK, Finn T, et al. Apoptosis fully accounts for the growth inhibitory properties of sulindac metabolites by a mechanism independent of cyclooxygenase inhibition, cell cycle arrest or p53 mediation. Cancer Res 1997; 57: 2452–2459.PubMedGoogle Scholar
  75. 75.
    Masferrer JL, Koki A, Seibert K. COX-2 inhibitors. A new class of antiangiogenic agents. Ann NY Acad Sci 1999; 889: 84–86.PubMedCrossRefGoogle Scholar
  76. 76.
    Kune GA. Colorectal cancer chemoprevention: aspirin, other NSAID and COX-2 inhibitors. Aust NZ J Surg 2000; 70: 452–455.CrossRefGoogle Scholar
  77. 77.
    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: 1220–1224.PubMedCrossRefGoogle Scholar
  78. 78.
    Sturner 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: 713–720.Google Scholar
  79. 79.
    Smalley W, Ray WA, Dougherty J, et al. Use of non-steroidal anti-inflammatory drugs and incidence of colorectal cancer. Arch Intern Med 1999; 159: 161–166.PubMedCrossRefGoogle Scholar
  80. 80.
    Torrance CJ, Jackson PE, Montgomery E, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000; 6: 1024–1028.PubMedCrossRefGoogle Scholar
  81. 81.
    Reddy BS, Rao CV, Seibert K. Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res 1996; 56: 4566–4569.PubMedGoogle Scholar
  82. 82.
    Kawamori T, Rao CV, Seibert K, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998; 58: 409–412.PubMedGoogle Scholar
  83. 83.
    Teicher BA, Korbut TT, Menon K, et al. Cyclooxygenase and lipoxygenase inhibitors as modulators of cancer therapies. Cancer Chemother Pharmacol 1994; 33: 515–522.PubMedCrossRefGoogle Scholar
  84. 84.
    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; 34: 1250–1259.PubMedCrossRefGoogle Scholar
  85. 85.
    Soriano AF, Helfrich B, Chan DC, et al. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res 1999; 59: 6178–6184.PubMedGoogle Scholar
  86. 86.
    Hida T, Kozaki K, Muramatsu H, et al. Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines. Clin Cancer Res 2000; 6: 2006–2011.PubMedGoogle Scholar
  87. 87.
    Palayoor ST, Bump EA, Calderwood SK, et al. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res 1998; 4: 763–771.PubMedGoogle Scholar
  88. 88.
    Milas L, Furuta Y, Hunter N, et al. Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence. Cancer Res 1990; 50: 4473–4477.PubMedGoogle Scholar
  89. 89.
    Furuta Y, Hunter N, Barkley T Jr, et al. Increase in radioresponse of murine tumors by treatment with indomethacin. Cancer Res 1988; 48: 3008–3013.PubMedGoogle Scholar
  90. 90.
    Kishi K, Petersen S, Petersen C, et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 2000; 60: 1326–1331.PubMedGoogle Scholar
  91. 91.
    Milas L, Kishi K, Hunter N, et al. Enhancement of tumor response to y-radiation by an inhibitor of cyclooxygenase-2 enzyme. J Natl Cancer Inst 1999; 91: 1501–1504.PubMedCrossRefGoogle Scholar
  92. 92.
    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; 6: 2513–2520.PubMedGoogle Scholar
  93. 93.
    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 which express cyclooxygenase-2. Submitted for publication to Clin Cancer Res 2001.Google Scholar
  94. 94.
    Lipsky PE, Isakson PC. Outcome of specific COX-2 inhibition in rheumatoid arthritis. J Rheumatol 1997; 24 (Suppl 49): 9–14.Google Scholar
  95. 95.
    Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999; 282: 1921–1928.PubMedCrossRefGoogle Scholar
  96. 96.
    Leese PT, Hubbard RC, Karim A, et al. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: arandomized, controlled trial. J Clin Pharmacol 2000; 40: 124–132.PubMedCrossRefGoogle Scholar
  97. 97.
    Bunn PA, Soriano A, Johnson G, et al. New therapeutic strategies for lung cancer: biology and molecular biology come of age. Chest 2000; 117: 163S - 168S.PubMedCrossRefGoogle Scholar
  98. 98.
    Zhang L, Hung MC. Sensitization of HER-2/neu-over-expressing non-small cell lung cancer cell to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Onco gene 1996; 12: 571–576.Google Scholar
  99. 99.
    Kroning R, Jones JA, Hom DK, et al. Enhancement of drug sensitivity of human malignancies by epidermal growth factor. Br J Cancer 1995; 72: 615–619.PubMedCrossRefGoogle Scholar
  100. 100.
    Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER-2/neu receptor modulates repair of radiation induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999; 59: 1347–1355.PubMedGoogle Scholar
  101. 101.
    Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 2001; 120 (7): 1713–1719.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Hong Pyo
  • Raymond N. DuBois
  • Hak Choy

There are no affiliations available

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