COX-2 and its inhibition as a molecular target in the prevention and treatment of lung cancer

Expert Review of Anticancer Therapy

Volumn 4, Issue 4, 2004, Pages 543-560

  Liao, Zhongxing ^a   Milas, Luka ^b  

^a UNIVERSITY OF TEXAS   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Chemotherapy; COX 2; COX 2 inhibitors; Lung cancer; Radiotherapy

Indexed keywords

4 [5 (4 CHLOROPHENYL) 3 TRIFLUOROMETHYL 1H PYRAZOL 1 YL]BENZENESULFONAMIDE; ACETYLSALICYLIC ACID; ANGIOGENESIS INHIBITOR; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; CARBOPLATIN; CELECOXIB; CETUXIMAB; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; DAUNORUBICIN; DOCETAXEL; DOXORUBICIN; EPIRUBICIN; ETOPOSIDE; IBUPROFEN; INDOMETACIN; IRINOTECAN; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; NAPROXEN; NIMESULIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PACLITAXEL; PIROXICAM; PROSTAGLANDIN; ROFECOXIB; UNCLASSIFIED DRUG; VINCRISTINE;

ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CAUSE OF DEATH; CLINICAL PROTOCOL; CLINICAL TRIAL; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DIGESTIVE SYSTEM ULCER; DRUG MECHANISM; DRUG POTENTIATION; DRUG SELECTIVITY; DRUG TARGETING; ENZYME INHIBITION; ESOPHAGITIS; GASTROINTESTINAL DISEASE; GASTROINTESTINAL HEMORRHAGE; HEART INFARCTION; HUMAN; HYPERTENSION; LUNG CANCER; LUNG CARCINOGENESIS; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR DYNAMICS; NAUSEA; NONHUMAN; PNEUMONIA; PRECANCER; PROSTAGLANDIN SYNTHESIS; PROTEIN EXPRESSION; REVIEW; TREATMENT OUTCOME; UNITED STATES;

EID: 4444262578     PISSN: 14737140     EISSN: None     Source Type: Journal    
DOI: 10.1586/14737140.4.4.543     Document Type: Review

References (146)

1. American Cancer Society. Cancer Facts & Figures. CRC Press, FL, USA (2001).
2. Dillman RO, Herndon J, Seagren SL, Eaton WL, Green MR. Improved survival in Stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J. Natl Cancer Inst. 88(17), 1210-1215 (1996).
3. Furuse Y, Fukuoka M, Kawahara M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable Stage III non-small cell lung cancer. J. Clin. Oncol. 17(9), 2692-2699 (1999).
4. Curran WJ. Sequential versus concurrent chemoradiation in unresected Stage III NSCLC: RTOG 94-10 initial report. J. Clin. Oncol. 19, 484a (2000).
5. Komaki R, Lee JS, Milas L et al. Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial 1. Int. J. Radiat. Oncol. Biol. Phys. 58(5), 1369-1377 (2004).
6. 2 synthase (cyclooxygenase) in human monocytes. J. Biol. Chem. 265, 16737-16740 (1990).
7. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am. J. Physiol. 270, G393-G400 (1996).
8. O'Banion MK. Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit. Rev. Neurobiol. 13, 45-82 (1999).
9. Garavito R. The cyclooxygenase-2 structure: new drugs for an old target? Nature Struct. Biol. 3, 897-901 (1996).
10. Otto J, DeWitt D, Smith W. N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum. J. Biol. Chem. 268(24), 18234-18242 (1993).
11. Milas L. Cyclooxygenase-2 (COX-2) enzyme inhibitors and radiotherapy. Am. J. Clin. Oncol. 26, S66-S69 (2003).
12. Marnett J. Cyclooxyenase mechansisms. Curr. Opin. Chem. Biol. 4, 545-552 (2000).
13. Bakhle Y. COX-2 and cancer: a new approach to an old problem. Br. J. Pharmacol. 134, 1137-1150 (2001).
14. Dannhardt G, Kiefer W. Cyclooxygenase inhibitors - current status and future prospects. Eur. J. Med. Chem. 36, 109-126 (2001).
15. Subbaramaiah K, Dannenberg A. Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol. Sci. 24, 96-102 (2003).
16. Komaki R, Liao Z, Milas L. Improvement strategies for molecular targeting: cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer. Semin. Oncol. 31(1 Suppl. 1), 47-53 (2004).
17. Liao Z, Komaki P, Mason K, Milas L. Role of cyclooxygenase-2 inhibitors in combination with radiation therapy in lung cancer. Clin. Lung Cancer 4, 356-365 (2003).
18. Gilman AG. G proteins: transducers of receptor-generated signals. Ann. Rev. Biochem. 56, 615-649 (1987).
19. Smith WL. The eicosanoids and their biochemical mechanisms of action. Biochem. J. 259(2), 315-324 (1989).
20. Lemberger T, Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Ann. Rev. Cell Dev. Biol. 12, 335-363 (1996).
21. Kliewer S, Forman B, Blumberg B et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl Acad. Sci. 91(15), 7355-7359 (1994).
22. Lim H, Gupta RA, Ma W-G et al. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPAR-δ. Genes Dev. 13(12), 1561-1574 (1999).
23. Giovannucci E, Rimm E, Stampfer M et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann. Intern. Med. 121, 241-246 (1994).
24. Thun M, Namboodiri M, Calle E, Flanders W, Heath C. Aspirin use and risk of fatal cancer. Cancer Res. 53, 1322-1327 (1993).
25. Bansal P, Sonnenberg A. Risk factors of colorectal cancer in inflammatory bowel disease. Am. J. Gastroenterol. 91, 44-48 (1996).
26. Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5(2), 138-146 (1994).
27. Eberhart C, Coffey R, Radhika A et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107, 1183-1188 (1994).
28. Koki A, Leahy RM, Masferrer JL. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin. Investig. Drugs 8(10), 1623-1638 (1999).
29. Oshima M, Dinchuk JE, Kargman SL et al. Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87, 803-809 (1996).
30. Liu CH, Chang S-H, Narko K et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J. Biol. Chem. 276(21), 18563-18569 (2001).
31. Jacoby RF, Seibert K, Cole CE, Kelloff G, Lubet RA. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the Min mouse model of adenomatous polyposis. Cancer Res. 60(18), 5040-5044 (2000).
32. Oshima M, Murai N, Kargman S et al. Chemoprevention of intestinal polyposis in the ApcΔ716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res. 61(4), 1733-1740 (2001).
33. 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. 25(4), 231-240 (1999).
34. Harris RE, Alshafie GA, Abou-Issa H, Seibert K. Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Cancer Res. 60(8), 2101-2103 (2000).
35. Dannenberg A. Subbaramaiah K. Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4, 431-436 (2003).
36. Alshafie G, Abou-Issa H, Seibert K, Harris R. Chemotherapeutic evaluation of celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model. Oncol. Rep. 7, 1377-1378 (2000).
37. Eling TE, Curtis JF. Xenobiotic metabolism by prostaglandin H synthase. Pharmacol. Ther. 53, 261-273 (1992).
38. Wiese FW, Thompson PA, Kadlubar FF. Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis 22(1), 5-10 (2001).
39. Rioux N, Castonguay A. Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Clin Res. 58, 5354-5360 (1998).
40. Muscat J, Chen S, Richie JJ et al. Risk of lung carcinoma among users of nonsteroidal anti-inflammatory drugs. Cancer 97, 1732-1736 (2003).
41. Harris R, Beebe-Donk J, Schuller H. Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among cigarette smokers. Oncol. Rep. 9(4), 693-695 (2002).
42. 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. 60(20), 5599-5602 (2000).
43. Shiotani H, Denda A, Yamamoto K et al. Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res. 61(4), 1451-1456 (2001).
44. Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 58, 409-412 (1998).
45. 2 enhance peripheral blood lymphocyte IL-10 transcription and protein production. J. Immunol. 157, 5512-5520 (1996).
46. 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. 58, 1208-1216 (1998).
47. Hida T, Yatabe Y, Achiwa H et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 58, 3761-3764 (1998).
48. Watkins D, Lenzo J, Segal A et al. Expression and localization of cyclooxygenase isoforms in non-small cell lung cancer. Eur. Respir. J. 14, 412-418 (1999).
49. Wolff H, Saukkonen K, Anttila S et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 58, 4997-5001 (1998).
50. Furuta Y, Hall ER, Sanduja S, Barkley TJ, Milas L. Prostaglandin production by murine tumors as a predictor for therapeutic response to indomethacin. Cancer Res. 48, 3002-3007 (1988).
51. Bennett A, Berstock DA, Raja B, Stamford IF. Survival time after surgery is inversely related to the amounts of prostaglandins extracted from human breast cancers. Br. J. Pharmacol. 66, 451 (1979).
52. Rigas B, Goldman IS, Levine L. Altered eicosanoid levels in human colon cancer. J. Lab. Clin. Med. 122, 518-523 (1993).
53. Sheehan KM, Sheahan K, O'Donoghue DP et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282, 1254-1257 (1999).
54. Murata H, Kawano S, Tsuji S et al. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am. J. Gastroenterol. 94(2), 451-455 (1999).
55. Zimmerman K, Sarbia M, Weber A et al. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res. 59, 198-204 (1999).
56. Wilson K, Fu S, Ramanujam K, Meltzer S. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barret's esophagus and associated adenocarcinomas. Cancer Res. 58, 2929-2934 (1998).
57. Achiwa H, Yatabe Y, Hida T et al. Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas. Clin. Cancer Res. 5(5), 1001-1005 (1999).
58. 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. 7(4), 861-867 (2001).
59. Yamauchi T, Watanabe M, Hasegawa H et al. The role of COX-2 expression in colorectal cancer. Proc. Am. Assoc. Cancer Res. (2000) (Abstract 41).
60. Brabender J, Park J, Metzger R et al. Prognostic significance of cyclooxygenase 2 mRNA expression in non-small cell lung cancer. Ann. Surg. 235, 440-443 (2001).
61. Ochiai M, Oguri T, Isobe T, Ishioka S, Yamakido M. Cyclooxygenease-2 mRNA expression levels in normal lung tissue and non-small cell cancers. Jpn. J. Cancer Res. 90, 1338-1343 (1999).
62. Soslow R, Dannenberg A, Rush D et al. COX-2 is expressed in human pulmonary, colonic, and mamary tumors. Cancer 89, 2637-2645 (2000).
63. Hasturk S, Kemp B, Kalapurakal S et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and non-small cell lung carcinoma. Cancer 94(4), 1023-1029 (2002).
64. Tang D, Honn KV. Eicosanoids and Tumor Cell Metastasis. CRC Press, FL, USA, 73-1108 (994).
65. Kozaki K, Koshikawa K, Tatematsu Y et al. Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis. Oncogene 20, 4228-4234 (2001).
66. Kakiuchi Y, Tsuji S, Tsujii M et al. Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Cancer Res. 62, 1567-1572 (2002).
67. Niki T, Kohno T, Iba S et al. Frequent colocalization of Cox-2 and laminin-5 γ2 chain at the invasive front of early-stage lung adenocarcinomas. Am. J. Pathol. 160(3), 1129-1141 (2002).
68. Okawa T, Kita M, Tanaka M, Ikeda M. Results of radiotherapy for inoperable locally advanced esophageal cancer. Int. J. Radiat. Oncol. Biol. Phys. 17, 49-54 (1989).
69. Williams CS, Isujii M, Reese J, Dey SK, DuBois RN. Host cyclooxygenase-2 modulates carcinoma growth. J. Clin. Invest. 105(11), 1589-1594 (2000).
70. Lin MT, Lee RC, Yang PC, Ho FM, Kuo ML. Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells involvement of phosphatidylinositol 3-kinase/atk pathway. J. Biol. Chem. 276(52), 48997-49002 (2001).
71. Dohadwala M, Luo J, Zhu L et al. Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. J. Biol. Chem. 276(24), 20809-20812 (2001).
72. 2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. J. Biol. Chem. 277(52), 50828-50833 (2002).
73. Yamaguchi N, Lichtenfels A, Demarchi L et al. COX-2, MMP-9, and Noguchi classification provide additional prognostic information about adenocarcinoma of the lung. A study of 117 patients from Brazil. Am. J. Clin. Pathol. 121, 78-86 (2004).
74. Tsubouchi Y, Mukai S, Kawahito Y et al. Meloxicam inhibits the growth of non-small cell lung cancer. Anticancer Res. 20, 2867-2872 (2000).
75. Fulton AM. Interactions of natural effector cells and prostaglandins in the control of metastasis. J. Natl Cancer Inst. 78, 735-741 (1987).
76. Masferrer JL, Leahy KM, Koki AT et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 60(5), 1306-1311 (2000).
77. Shaik M, Chatterjee A, Singh M. Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ. Clin. Cancer Res. 10, 1521-1529 (2004).
78. Marnett L. Generation of mutagens during arachidonic acid metabolism. Cancer Metastasis Rev. 13(3-4), 303-308 (1994).
79. Prescott S, White R. Self-promotion? Intimate connections between APC and prostaglandin H synthase-2. Cell 87, 783-786 (1996).
80. Watson AJ. Chemopreventive effects of NSAIDs against colorectal cancer: regulation of apoptosis and mitosis by COX-1 and COX-2. Histol. Histopathol. 13, 591-597 (1998).
81. Smith M-L, Hawcroft G, Hull MA. The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action. Eur. J. Cancer 36(5), 664-674 (2000).
82. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83(3), 493-501 (1995).
83. Dempke W, Rie C, Grothey A, Schmoll H. Cyclooxygenase-2: a novel target for cancer chemotherapy? J. Cancer Res. Clin. Oncol. 127, 411-417 (2001).
84. Krysan K, Merchant F, Zhu L et al. COX-2-dependent stabilization of surviving in non-small cell lung cancer. FASEB J. 18(1), 206-208 (2004).
85. 2 and angiogenesis. Proc. Soc. Exp. Biol. Med. 172, 214-218 (1983).
86. 1 and copper in angiogenesis. J. Natl Cancer Inst. 69, 475-482 (1982).
87. Majima M, Hayashi I, Muramatsu M et al. Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants. Br. J. Pharmacol 130(3), 641-649 (2000).
88. Rak J, Filmus J, Kerbel RS. Reciprocal paracrine interactions between tumour cells and endothelial cells: the angiogenesis progression hypothesis. Eur. J. Cancer 32A, 2438-2450 (1996).
89. Milas L, Furuta Y, Hunter N, Nishiguchi I, Runkel S. Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence. Cancer Res. 50, 4473-4477 (1990).
90. Milas L, Kishi K, Hunter N et al. Enhancement of tumor response to γ-radiation by an inhibitor of cyclooxygenase-2 enzyme. J. Natl Cancer Inst. 91(17), 1501-1504 (1999).
91. Leahy KM, Ornberg RL, Wang Y et al. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res. 62(3), 625-631 (2002).
92. Dicker A, Williams T, Grant D. Targeting angiogenic processes by combination rofecoxib and ionizing radiation. Am. J. Clin. Oncol. 24, 438-442 (2001).
93. Pold M, Zhu LX, Sharma S et al. Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer. Cancer Res. 64(5), 1853-1860 (2004).
94. Su J-L, Shih J-Y, Yen M-L et al. Cyclooxygenase-2 induces EP1- and HER-2/neu-dependent vascular endothelial growth factor-C up-regulation: a novel mechanism of lymphangiogenesis in lung adenocarcinoma. Cancer Res. 64(2), 554-564 (2004).
95. Leung KH, Mihich E. Prostaglandin modulation of development of cell-mediated immunity in culture. Nature 288, 597-600 (1980).
96. Brunda M, Herberman R, Holden H. Inhibition of murine natural killer cell activity by prostaglandins. J. Immunol. 124(6), 2682-2687 (1980).
97. Fulton AM, Levy JG. The possible role of prostaglandins in mediating immune suppression by nonspecific T suppressor cells. Cell Immunol. 52, 29-37 (1980).
98. 2 inhibits TNF-α release via a mechanism involving IL-10. J. Immunol. 154, 3383-3390 (1995).
99. Stolina M, Sharma S, Lin Y et al. Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J. Immunol. 164(1), 361-370 (2000).
100. Heuze-Vourch N, Zhu L, Krysan K et al. Abnormal interleukin 10Rα expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells. Cancer Res. 63(4), 766-770 (2003).
101. Sharma S, Stolina M, Yang S-C et al. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin. Cancer Res. 9(3), 961-968 (2003).
102. Yang L, Yamagata N, Yadav R et al. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J. Clin. Invest. 111(5), 727-735 (2003).
103. Milas L, Nishiguchi I, Hunter N et al. Radiation protection against early and late effects of ionizing irradiation by the prostaglandin inhibitor indomethacin. Adv. Space Res. 12, 265-271 (1992).
104. Hanson WR. Eicosanoid-induced radioprotection and chemoprotection: laboratory studies and clinical applications. In: Radioprotectors: Chemical, Bioligical and Clinical Perspectives. Bump EA, Malaker K (Eds), CRC Press, FL, USA, 197-221 (1998).
105. Milas L, Hanson W. Eicosanoids and radiation. Eur. J. Cancer 31A, 1580-1585 (1995).
106. 1 analog misoprostol in DNA repair-proficient and -deficient rodent cell systems. Radiat. Res. 152, 398-403 (1999).
107. 2 (nocloprost) on the radiation response of human normal fibroblasts and colon adenocarcinoma cells. Radiat. Res. 135, 88-92 (1993).
108. 2 increases survival of murine intestinal stem cells when given before photon radiation. Radiat. Res. 96, 393-398 (1983).
109. Hanson W, Geng L, Malkinson F. Prostaglandin-induced protection from radiation or doxorubicin is tissue specific and dependent upon receptor expression. Int. Congress Radiat. Res. (1995) (Abstract 435).
110. 2 or WR-2721 (WR-1065) protects mice from alopecia after fractionated irradiation. Int. J. Radiat. Biol. 61, 533-537 (1992).
111. van Buul PP, van Duyn-Goedhart A, de Rooij DG, Sankaranarayanan K. Differential radioprotective effects of misoprostol in DNA repair-proficient and -deficient or radiosensitive cell systems. Int. J. Radiat. Biol. 71, 259-264 (1997).
112. Houchen CW, Stenson WF, Cohn SM. Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury. Am. J. Physiol. Gastrointest. Liver Physiol. 279(5), G858-G865 (2000).
113. Furuta Y, Hunter N, Barkley T Jr, Hall E, Milas L. Increase in radioresponse of murine tumors by treatment with indomethacin. Cancer Res. 48, 3008-3013 (1988).
114. Kishi K, Petersen S, Petersen C et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 60(5), 1326-1331 (2000).
115. Petersen C, Petersen S, Milas L, Lang FF, Tofilon P. Human glioma cell radiosensitization by a selective COX-2 inhibitor. Clin. Cancer Res. 6, 2513-2520 (2000).
116. 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. 7, 2998-3005 (2001).
117. Davis T, Hunter N, Trifan OC, Milas L. COX-2 inhibitors as radiosensitizing agents for cancer therapy. Am. J. Clin. Oncol. 26(4), S58-S61 (2003).
118. Amirghahari N, Harrison L, Smith M et al. NS 398 radiosensitizes an HNSCC cell line by possibly inhibiting radiation-induced expression of COX-2. Int. J. Radiat. Oncol. Biol. Phys. 57(5), 1405-1412 (2003).
119. Wen B, Deutsch E, Eschwege P et al. Cyclooxygenase-2 inhibitor NS398 enhances antitumor effect of irradiation on hormone refractory human prostate carcinoma cells. J. Urol. 170, 2036-2039 (2003).
120. Raju U, Nakata E, Yang P et al. In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations. Int. J. Radiat. Oncol. Biol. Phys. 54(3), 886-894 (2002).
121. Milas L, Mason K, Hunter N et al. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin. Cancer Res. 6, 701-708 (2000).
122. Gorski DH, Mauceri HJ, Salloum RM et al. Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res. 58, 5686-5689 (1998).
123. Gorski DH, Beckett MA, Jaskowiak NT et al. Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 59(14), 3374-3378 (1999).
124. Teicher BA, Holden SA, Dupuis NP et al. Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma. Breast Cancer Res. Treat. 36, 227-236 (1995).
125. Manson MM, Holloway KA, Howells LM et al. Modulation of signal-transduction pathways by chemopreventive agents. Biochem. Soc. Trans. 28, 7-12 (2000).
126. Li L, Rojiani A, Siemann DW. Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: effects on radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 42, 335-363 (1998).
127. Haimovitz-Friedman A, Vlodavsky I, Chaudhuri A, Witte L, Fuks Z. Autocrine effects of fibroblast growth factor in repair of radiation damage in endothelial cells. Cancer Res. 51, 2552-2558 (1991).
128. Steinauer KK, Gibbs I, Ning S et al. Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells. Int. J. Radiat. Oncol. Biol. Phys. 48(2), 325-328 (2000).
129. Torrance CJ, Jackson PE, Montgomery E et al. Combinatorial chemoprevention of intestinal neoplasia. Nature Med. 6, 1024-1028 (2000).
130. Harari PM, Huang SM. Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Semin. Radiat. Oncol. 11, 281-290 (2001).
131. Duffy C, Elliott C, O'Connor R et al. Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of non-steroidal anti-inflammatory drug, (NSAIDs). Eur. J. Cancer 34(8), 1250-1259 (1998).
132. Trifan OC, Durham WF, Salazar VS et al. Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11. Cancer Res. 62(20), 5778-5784 (2002).
133. Nakata E, Mason K, Hunter N et al. Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors. Int. J. Radiat. Oncol. Biol. Phys. 58, 369-375 (2004).
134. Patel VA, Dunn MJ, Sorokin A. Regulation of MDR-1 (P-glycoprotein) by cyclooxygenase-2. J. Biol. Chem. 277(41), 38915-38920 (2002).
135. Ratnasinghe D, Daschner P, Anver M et al. Cyclooxygenase-2, P-glycoprotein-170 and drug resistance: is chemoprevention against multidrug resistance possible? Anticancer Res. 21, 2141-2147 (2001).
136. Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib versus nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 284(10), 1247-1255 (2000).
137. Cleland LG, James MJ, Stamp LK, Penglis PS. COX-2 inhibition and thrombotic tendency: a need for surveillance. Med. J. Aust. 175, 214-217 (2001).
138. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286(8), 954-959 (2001).
139. Howes LG, Krum H. Selective cyclooxygenase-2 inhibitors and myocardial infarction: how strong is the link? Drug Saf. 25(12), 829-835 (2002).
140. Liao Z, Chen Y, Komaki R, Cox J, Milas L. A Phase I study combining thoracic radiation (RT) with celecoxib in patients with non-small cell lung cancer (NSCLC). Proc. Am. Soc. Clin. Oncol. 22 (2003) (Abstract 216).
141. Csiki I, Dang T, Gonzalez A. Cyclooxygenase-2 (COX-2) inhibition plus docetaxel (Txt) in recurrent non-small cell lung cancer (NSCLC): preliminary results of a Phase II trial (THO-0054). Proc. Am. Soc. Clin. Oncol 21, 297a (2002) (Abstract 1187).
142. Laskin J, Sandler A. The importance of the eicosanoid pathway in lung cancer. Lung Cancer 41, 573-579 (2003).
143. Altorki NK, Keresztes RS, Port JL et al. Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. J. Clin. Oncol. 21(14), 2645-2650 (2003).
144. Carbone D, Choy H, Csiki I. Serum/plasma VEGF level changes with cyclooxygenase-2 (COX-2) inhibition in combined modality therapy in Stage III non-small cell lung cancer (NSCLC): preliminary results of a Phase II trial (THO-0059). Proc. Am. Soc. Clin. Oncol. (2002) (Abstract 1270).
145. 2 and interleukin-10 production in alveolar macrophages from active smokers. Clin. Cancer Res. 9(16), 5835-5841 (2003).
146. Blanke C, Masferrer J. Chemotherapy with cyclooxygenase-2 inhibitors in the treatment of malignant disease: preclinical rational and preliminary results of clinical trials. Prog. Exp. Tumor Res. 37, 243-260 (2003).