Cyclooxygenase-2(COX-2) - A therapeutic target in liver cancer?

Current Pharmaceutical Design

Volumn 13, Issue 32, 2007, Pages 3305-3315

  Breinig, Marco ^a   Schirmacher, Peter ^a   Kern, Michael A ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

Growth Factor Signaling; Immune responses; NSAIDs; Proliferation; Prostaglandins

Indexed keywords

BETA INTERFERON; CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; ETODOLAC; FLURBIPROFEN; IBUPROFEN; INDOMETACIN; MELOXICAM; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; NIMESULIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN; SULINDAC;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER INHIBITION; CANCER INVASION; CELL PROLIFERATION; COLON CANCER; CYTOTOXICITY; DRUG TARGETING; ENZYME PHOSPHORYLATION; HIGH RISK POPULATION; HUMAN; IMMUNOMODULATION; INCIDENCE; LIVER CANCER; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; METASTASIS INHIBITION; MORTALITY; NONHUMAN; PRIORITY JOURNAL; PROSTAGLANDIN METABOLISM; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SURVIVAL RATE;

APOPTOSIS; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; DRUG RESISTANCE, NEOPLASM; HUMANS; LIVER NEOPLASMS; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NEOVASCULARIZATION, PATHOLOGIC; PROSTAGLANDINS; SIGNAL TRANSDUCTION;

EID: 36749085341     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161207782360627     Document Type: Review

References (165)

1. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer 2006; 6: 674-87.
2. Seeff LB, Hoofhagle JH. Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity. Oncogene 2006; 25: 3771-7.
3. El-Serag HB. Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 2002; 36: S74-83.
4. El-Serag HB. Hepatocellular carcinoma: An epidemiologic view. J Clin Gastroenterol 2002; 35: S72-8.
5. El-Serag HB. Hepatocellular carcinoma: Recent trends in the United States. Gastroenterology 2004; 127: S27-34.
6. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907-17.
7. Velazquez RF, Rodriguez M, Navascues CA, Linares A, Perez R, Sotorrios NG, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 2003; 37: 520-7.
8. Nair S, Mason A, Eason J, Loss G, Perrillo RP. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 2002; 36: 150-5.
9. El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: A systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006; 4: 369-80.
10. Yano Y, Yamashita F, Sumie S, Ando E, Fukumori K, Kiyama M, et al. Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan. Am J Gastroenterol 2002; 97: 156-61.
11. Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa, G, Craxi A, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 2004; 126: 102-10
12. Thomas MB, Abbruzzese JL. Opportunities for targeted therapies in hepatocellular carcinoma. J Clin Oncol 2005; 23: 8093-108.
13. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 2001; 41: 661-90.
14. Narumiya S, FitzGerald GA. Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest 2001; 108: 25-30.
15. Fletcher BS, Kujubu DA, Perrin DM, Herschman HR. Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase. J Biol Chem 1992; 267: 4338-44.
16. Hla T, Neilson K. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA 1992; 99: 7384-8.
17. Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA 1991; 88: 2692-6.
18. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural, cellular, and molecular biology. Annu Rev Biochem 2000; 69: 145-82.
19. Smith WL, Langenbach R. Why there are two cyclooxygenase isozymes. J Clin Invest 2001; 107: 1491-5.
20. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999; 18: 7908-16.
21. 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: 4399-404.
22. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231: 232-5.
23. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrcnbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107: 1183-8.
24. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995; 83: 493-501.
25. Urban MK. COX-2 specific inhibitors offer improved advantages over traditional NSAIDs. Orthopedics 2000; 23: S761-4.
26. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E et al Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 97: 803-9.
27. Reddy BS, Rao CV, Seibert K. Evaluation of cyclooxygenase-2 inhibitor for potential chemopreventive properties in colon carcinogenesis. Cancer Res 1996; 56: 4566-9.
28. Sheng GG, Shao J, Sheng H, Hooton EB, Isakson PC, Morrow JD, et al. A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells. Gastroenterology 1997; 113: 1883-91.
29. Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, et al. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997; 99: 2254-9.
30. Turini ME, DuBois RN. Cyclooxygenase-2: A therapeutic target. Annu Rev Med 2002; 53: 35-57.
31. Koga H, Sakisaka S, Ohishi M, Kawaguchi T, Taniguchi E, Sasatomi K, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: Relevance to tumor dedifferentiation. Hepatology 1999; 29: 688-96.
32. Bae SH, Jung ES, Park YM, Kim BS, Kim BK, Kim DG, 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: 1410-8.
33. Foster J, Black J, Levea C, Khoury T, Kuvshinoff B, Javle M, et al. COX-2 expression in hepatocellular carcinoma is an initiation event; while EGF receptor expression with downstream pathway activation is a prognostic predictor of survival. Ann Surg Oncol 2007; 14: 752-8
34. Kondo M, Yamamoto H, Nagano H, Okami J, Ito Y, Shimizu J, 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: 4005-12.
35. Sung YK, Hwang SY, Kim JO, Bae HI, Kim JC, Kim MK. The correlation between cyclooxygenase-2 expression and hepatocellular carcinogenesis. Mol Cells 2004; 17: 35-8.
36. Tang TC, Poon RT, Lau CP, Xie D, Fan ST. Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma. World J Gastroenterol 2005; 11: 1896-902.
37. Morinaga S, Yamamoto Y, Noguchi Y, Imada T, Rino Y, Akaike M, et al. Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma. J Gastroenterol Hepatol 2002; 17: 1110-6.
38. Cervello M, Foderaa D, Florena, AM, Soresi M, Tripodo C, D'Alessandro N, et al. Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: Possible role in tumor promotion and angiogenesis. World J Gastroenterol 2005; 11: 4638-43.
39. Marchio A, Meddeb M, Pineau P, Danglot G, Tiollais P, Bernheim A, et al. Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 1997; 18: 59-65.
40. Niketeghad F, Decker HJ, Caselmann WH, Lund P, Geissler F, Dienes HP, et al. Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis. Br J Cancer 2001; 85: 697-704.
41. Murata H, Tsuji S, Tsujii M, Sakaguchi Y, Fu HY, Kawano S, et al. Promoter hypermethylation silences cyclooxygenase-2 (Cox-2) and regulates growth of human hepatocellular carcinoma cells. Lab Invest 2004; 84: 1050-9.
42. de Ledinghen V, Liu H, Zhang F, Lo CR, Subbaramaiah K, Dannenberg AJ, et al. Induction of cyclooxygenase-2 by tumor promoters in transformed and cytochrome P450 2E1-expressing hepatocytes. Carcinogenesis 2002; 23: 73-9.
43. Callejas NA, Busca, L, Williams CS, Du BR, Martin-Sanz P. Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins. Gastroenterology 2000; 119: 493-501.
44. Araki Y, Okamura S, Hussain SP, Nagashima M, He P, Shiseki M, et al. Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. Cancer Res 2003; 63: 728-34.
45. Xu L, Han C, Lim K, Wu T. Cross-talk between peroxisome proliferator-activated receptor delta and cytosolic phospholipase A(2)alpha/cyclooxygenase-2/prostaglandin E(2) signaling pathways in human hepatocellular carcinoma cells. Cancer Res 2006; 66: 11859-68
46. Lara-Pezzi E, Gomez-Gaviro MV, Galvez BG, Mira E, Iniguez MA, Fresno M, et al. The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. J Clin Invest 2002; 110: 1831-8.
47. Cervello M, Montalto G. Cyclooxygenases in hepatocellular carcinoma. World J Gastroenterol 2006; 12: 5113-21.
48. Wu T. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat Rev 2006; 32: 28-44.
49. Rahman MA, Kohno H, Nagasue N. COX-2 - a target for preventing hepatic carcinoma? Expert Opin Ther Targets 2002; 6: 483-90.
50. Hu KQ. Rationale and feasibility of chemoprovention of hepatacellular carcinoma by cyclooxygenase-2 inhibitors. J Lab Clin Med 2002; 139: 234-43.
51. Chi-Man Tang T, Tung-Ping Poon R, Fan ST. The significance of cyclooxygenase-2 expression in human hepatocellular carcinoma. Biomed Pharmacother 2005; 59(Suppl 2): S311-6.
52. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
53. Crosby CG, DuBois RN. The cyclooxygenase-2 pathway as a target for treatment or prevention of cancer. Expert Opin Emerg Drugs 2003; 8: 1-7.
54. Dannenberg AJ, Altorki NK, Boyle JO, Dang C, Howe LR, Weksler BB, et al. Cyclo-oxygenase 2: A pharmacological target for the prevention of cancer. Lancet Oncol 2001; 2: 544-51.
55. Evans JF, Kargman SL. Cancer and cyclooxygenase-2 (COX-2) inhibition. Curr Pharm Des 2004; 10: 627-34.
56. Breuhahn K, Longerich T, Schirmacher P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 2006; 25: 3787-800.
57. Roberts LR, Gores GJ. Hepatocellular carcinoma: Molecular pathways and new therapeutic targets. Semin Liver Dis 2005; 25: 212-25.
58. Gschwind A, Zwick E, Prenzel N, Leserer M, Ullrich A. Cell communication networks: Epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission. Oncogene 2001; 20: 1594-600.
59. Piiper A, Zeuzem S. Receptor tyrosine kinases are signaling intermediates of G protein-coupled receptors. Curr Pharm Des 2004; 10: 3539-45.
60. Schafer B, Gschwind A, Ullrich A. Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene 2004; 23: 991-9.
61. Abiru S, Nakao K, Ichikawa T, Migita K, Shigeno M, Sakamoto M, et al. Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma, cells. Hepatology 2002; 35: 1117-24
62. Han C, Michalopoulos GK, Wu T. Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J Cell Physiol 2006; 207: 261-70.
63. Igney FH, Krammer PH. Death and anti-death: Tumour resistance to apoptosis. Nat Rev Cancer 2002; 2: 277-88.
64. Fleischer B, Schulze-Bergkamen H, Schuchmann M, Weber A, Biesterfeld S, Mullet M. et al. Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma. Int J Oncol 2006; 28: 25-32.
65. Lee SH, Shin MS, Lee HS, Bae JH, Lee HK, Kim HS, et al. Expression of Fas and Fas-related molecules in human hepatocellular carcinoma. Hum Pathol 2001; 32: 250-6.
66. Morinaga, S, Nakamura Y, Ishiwa N, Yoshikawa T, Noguchi Y, Yamamoto Y, et al. Expression of survivin mRNA associates with apoptosis, proliferation and histologically aggressive features in hepatocellular carcinoma. Oncol Rep 2004; 12: 1189-94.
67. Shen HW, Gao SL, Wu YL, Peng SY. Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis. World J Gastroenterol 2005; 11: 5926-30.
68. Shin EC, Shin JS, Park JK Kim JJ, Kim H, Kim SJ. Expression of Fas-related genes in human hepatocellular carcinomas. Cancer Lett 1998; 134: 155-62.
69. Takehara T, Liu X, Fujimoto J, Friedman SL, Takahashi H. Expression and role of Bel-xL in human hepatocellular carcinomas. Hepatology 2001; 34: 55-61.
70. Watanabe J, Kushihata F, Honda Y, Mominoki K, Matsuda S, Kobayashi N. Bcl-xL overexpression in human hepatocellular carcinoma. Int J Oncol 2002; 21: 515-9.
71. Cheng J, Imanishi H, Amuro Y, Hada T. NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines. Int J Cancer 2002; 99: 755-61.
72. Cheng J, Imanishi H, Liu W, Nakamura H, Morisaki T, Higashino K, et al. Involvement of cell cycle regulatory proteins and MAP kinase signaling pathway in growth inhibition and cell cycle arrest by a selective cyclooxygenase 2 inhibitor, etodolac, in human hepatocellular carcinoma cell lines. Cancer Sci 2004; 95: 666-73.
73. Cui W, Yu CH, Hu KQ. In vitro and in vivo effects and mechanisms of celecoxib-induced growth inhibition of human hepatocellular carcinoma cells. Clin Cancer Res 2005; 11: 8213-21.
74. Fodera D, D'Alessandro N, Cusimano A, Poma P, Notarbartolo M, Lampiasi N, et al. Induction of apoptosis and inhibition of cell growth in human hepatocellular carcinoma cells by COX-2 inhibitors. Ann N Y Acad Sci 2004; 1028: 440-9.
75. Hu KQ, Yu CH, Mineyama Y, McCracken JD, Hillebrand DJ, Hasan M. Inhibited proliferation of cyclooxygenase-2 expressing human hepatoma cells by NS-398, a selective COX-2 inhibitor. Int J Oncol 2003; 22: 757-63.
76. Huang DS, Shen KZ, Wei JF, Liang TB, Zheng SS, Xie HY. Specific COX-2 inhibitor NS398 induces apoptosis in human liver cancer cell line HepG2 through BCL-2. World J Gastroenterol 2005; 11: 204-7.
77. Kern MA, Schubert D, Sahi D, Schoneweiss MM, Moll I, Haugg AM, et al. Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells. Hepatology 2002; 36: 885-94.
78. Leng J, Han C, Demetris AJ, Michalopoulos GK, Wu T. Cyclooxygenase-2 promotes hepatocellular carcinoma cell growth through Akt activation: evidence for Akt inhibition in celecoxib-induced apoptosis. Hepatology 2003; 38: 756-68.
79. Park JW, Park JE, Lee JA, Lee CW, Kim CM. Cyclooxygenase-2 (COX-2) is directly involved but not decisive in proliferation of human hepatocellular carcinoma cells. J Cancer Res Clin Oncol 2006; 132: 184-92.
80. Park W Hwang SY, Kim JO, Kwack MH, Kim JC, Kim MY, et al. NS398 inhibits the growth of Hep3B human hepatocellular carcinoma cells via caspase-independent apoptosis. Mol Cells 2004; 17: 45-50
81. Rahman MA, Dhar DK, Masunaga R, Yamanoi A, Kohno, H, Nagasue N. Sulindac and exisulind exhibit a significant antiproliferative effect and induce apoptosis in human hepatocellular carcinoma cell lines. Cancer Res 2000; 60: 2085-9.
82. Tian G, Yu JP, Luo HS, Yu BP, Yuc H, Li JY, et al. Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells. World J Gastroenterol 2002; 8: 483-7.
83. Yamanaka Y, Shiraki K, Inoue T, Miyashita K, Fuke H, Yamaguchi Y, et al. COX-2 inhibitors sensitiz e human hepatocellular carcinoma cells to TRAEL-induced apoptosis. Int J Mol Med 2006; 18: 41-7.
84. Kern MA, Haugg AM, Koch AF, Schilling T, Breuhahn K, Walczak H, et al. Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma. Cancer Res 2006; 66: 7059-66.
85. Fernandez-Martinez A, Molla B, Mayoral R, Bosca L, Casado M, Martin-Satiz P. Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells. Biochem J 2006; 398: 371-80.
86. Lee JS, Thorgeirsson SS. Genome-scole profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets. Gastroenterology 2004; 127: S51-5.
87. Tannapfel A, Wittekind C. Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis. Virchows Arch 2002; 440: 345-52.
88. Wang XW, Hussain SP, Hun TI, Wu CG, Forgues M, Hofseth LJ, et al. Molecular pathogenesis of human hepatocellular carcinoma. Toxicology 2002; 181-182: 43-7.
89. Kern MA, Breuhahn K, Schirmacher P. Molecular pathogenesis of human hepatocellular carcinoma. Adv Cancer Res 2002; 86: 67-112.
90. Li J, Chen X, Dong X, Xu Z, Jiang H, Sun X. Specific COX-2 inhibitor, meloxicam, suppresses proliferation and induces apoptosis in human HepG2 hepatocellular carcinoma cells. J Gastroenterol Hepatol 2006; 21: 1814-20.
91. Giono LE, Manfredi JJ. The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol 2006; 209: 13-20.
92. North S, Hainaut P. p53 and cell-cycle control: A finger in every pie. Pathol Biol (Paris) 2000; 48: 255-70.
93. Abou-Shady M, Baer HU, Friess H, Zimmermann A, Buchler MW. Molecular aspects of hepatocellular carcinoma. Swiss Surg 1999; 5: 102-6.
94. Poon RT, Lau C, Yu WC, Fan ST, Wong J. High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: A prospective study. Oncol Rep 2004; 11: 1077-84.
95. Poon RT, Ng IO, Lau C, Yu WC, Yang ZF, Fan ST, et al. Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: A prospective study. J Clin Oncol 2002; 20: 1775-85.
96. Tanigawa N, Lu C, Mitsui T, Miura S. Quantitation of sinusoid-like vessels in hepatocellular carcinoma: Its clinical and prognostic significance. Hepatology 1997; 26: 1216-23.
97. Cheng AS, Chan HL, To KF, Leung WK, Chan KY, Liew CT, et al. Cyclooxygenase-2 pathway correlates with vascular endothelial growth factor expression and tumor angiogenesis in hepatitis B virus-associated hepatocellular carcinoma. Int J Oncol 2004; 24: 853-60.
98. Rahman MA, Dhar DK, Yamaguchi E, Maruyama S, Sato T, Hayashi H, 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: 1325-32.
99. Zhao QT, Yue SQ, Cui Z, Wang Q, Cui X, Zhai HH, et al. Potential involvement of the cyclooxygenase-2 pathway in hepatocellular carcinoma-associated angiogenesis. Life Sci 2007; 80: 484-92.
100. Amano, H, Hayashi I, Endo H, Kitasato H, Yamashina S, Maruyama T, et al. Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. J Exp Med 2003; 197: 221-32.
101. Majima M, Amano H, Hayashi I. Prostanoid receptor signaling relevant to tumor growth and angiogenesis. Trends Pharmacol Sci 2003; 24: 524-9
102. Mayoral R, Fernandez-Martinez A, Bosca L, Martin-Sanz P. Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells. Carcinogenesis 2005; 26: 753-61.
103. Yang L, Carbone DP. Tumor-host immune interactions and dendritic cell dysfunction. Adv Cancer Res 2004; 92: 13-27.
104. Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol 1983; 3: 295-315.
105. Nataraj C, Thomas DW, Tilley SL, Nguyen MT, Marmon R, Koller BH et al. Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest 2001; 108: 1229-35.
106. Narumiya S. Prostanoids in inummity: Roles revealed by mice deficient in their receptors. Life Sci 2003; 74: 391-5.
107. Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, et al. Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 2000; 164: 361-70.
108. Iwamoto A, Ikeguchi M, Matsumoto S, Hukumoto Y, Inoue M, Ozaki T, et al. Tumor cyclooxygenase-2 gene suppresses local immune responses in patients with hepatocellular carcinoma. Tumori 2006; 92: 130-3.
109. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421-30.
110. Johnson PJ. Hepatocellular carcinoma: Is current therapy really altering outcome? Gut 2002; 51: 459-62.
111. Bonin S, Pascolo L, Croce LS, Stanta G, Tiribelli C. Gene expression of ABC proteins in hepatocellular carcinoma, perineoplastic tissue, and liver diseases. Mol Med 2002; 8: 318-25.
112. Chenivesse X, Franco D, Brechot C. MDR1 (multidrug resistance) gene expression in human primary liver cancer and cirrhosis. J Hepatol 1993; 18: 168-72.
113. Wang BL, Chen XP, Zhai SP, Chen DF. Clinical significance of mrp gene in primary hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2003; 2: 397-403.
114. Minemura M, Tanimura H, Tabor E. Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines. Int J Oncol 1999; 15: 559-63.
115. Ng IO, Liu CL, Fan ST, Ng M. Expression of P-glycoprotein in hepatocellular carcinoma. A determinant of chemotherapy response. Am J Clin Pathol 2000; 113: 355-63.
116. Petraccia L, Onori P, Sferra R, Lucchetta MC, Liberati G, Grassi M, et al. [MDR (multidrug resistance) in hepatocareinoma clinical-therapeutic implications]. Clin Ter 2003; 154: 325-35.
117. Sorokin A. Cyclooxygenase-2: Potential role in regulation of drug efflux and multidrug resistance phenotype. Curr Pharm Des 2004; 10: 647-57
118. Fantappie O, Masini E, Sardi I, Raimondi L, Bani D, Solazzo M, et al. The MDR phenotype is associated with the expression of COX2 and iNOS in a human hepatocellular carcinoma cell line. Hepatology 2002; 35: 843-52.
119. Ziemann C, Schafer D, Rudell G, Kahl GF, Hirsch-Ernst KI. The cyclooxygenase system participates in functional mdr1b overexpression in primary rat hepatocyte cultures. Hepatology 2002; 35: 579-88.
120. Roberts LR, Gores GJ. Emerging drugs for hepatocellular carcinoma. Expert Opin Emerg Drugs 2006; 11: 469-87.
121. Nakamoto N, Higuchi H, Kanamori H, Kurita S, Tada S. Takaishi H, et al. Cyclooxygenase-2 inhibitor and interferon-beta synergistically induce apoptosis in human hepatoma cells in vitro and in vivo. Int J Oncol 2006; 29: 625-35.
122. Grosch S, Maier TJ, Schiffmarm S, Geisslinger G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Just 2006; 98: 736-47.
123. Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001; 1: 11-21.
124. Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, et al. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res 2004; 64: 4309-18.
125. Lin HP, Kulp SK, Tseng PH, Yang YT, Yang CC, Chen CS, et al. Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms. Mol Cancer Ther 2004; 3: 1671-80.
126. Johnson AJ, Hsu AL, Lin HP, Song X, Chen CS. The cyclooxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulurn Ca2+-ATPases: A plausible link with its anti-tumour effect and cardiovascular risks. Biochem J 2002; 366: 831-7.
127. Soh JW, Weinstein IB. Role of COX-independent targets of NSAIDs and related compounds in cancer prevention and treatment. Prog Exp Tumor Res 2003; 37: 261-85.
128. Tegeder I, Pfeilsehifter J, Geisslinger G. Cyclooxygenase-independent actions of cyclooxygenase inhibitors. FASEB J 2001; 15: 2057-72.
129. Zha S, Yegnasubramanian V, Nelson WG, Isaacs WB, De Marzo AM. Cyclooxygenases in cancer: Progress and perspective. Cancer Lett 2004; 215: 1-20.
130. Dent P, Yacoub A, Grant S. DMC: Novel celecoxib derivatives to rap cancer. Cancer Biol Ther 2005; 4: 583-4.
131. Lampiasi N, Fodera D, D'Alessandro N, Cusimano A, Azzolina A, Tripodo C, et al. The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells. Int J Mol Med 2006; 17: 245-52.
132. Kitamura T, Itoh M, Noda T, Matsuura M, Wakabayashi K. Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice. Int J Cancer 2004; 109: 576-80.
133. Kern MA, Schoneweiss MM, Sahi D, Bahlo M, Haugg AM, Kasper HU, et al. Cyclooxygenase-2 inhibitors suppress the growth of hurnan bepatocellular carcinoma implants in nude mice. Carcinogenesis 2004; 25: 1193-9.
134. Tanaka S, Wands JR, Arii S. Induction of angiopoietin-2 gene expression by COX-2: A novel role for COX-2 inhibitors during hepatocarcinogenesis. J Hepatol 2006; 44: 233-5.
135. Denda A, Kitayama W, Murata A, Kishida H, Sasaki Y, Kusuoka O, et al. Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide. Carcinogenesis 2002; 23: 245-56.
136. Marquez-Rosado L, Trejo-Solis MC, Garcia-Cuellar CM, Villa-Trevino S. Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats. J Hepatol 2005; 43: 653-60.
137. Liu W, Nakamura H, Tsujimura T, Cheng J, Yamamoto T, Iwamoto Y, et al. Chemoprevention of spontaneous development of hepatocellular carcinomas in fatty liver Shionogi mice by a cyclooxygenase-2 inhibitor. Cancer Sci 2006; 97: 768-73.
138. Kem MA, Haugg AM, Eiteneuer E, Konze E, Drebber U, Dienes HP, et al. Ex vivo analysis of antineoplastic agents in precision-cut tissue slices of human origin: Effects of cyclooxygenase-2 inhibition in hepatocellular carcinoma. Liver Int 2006; 26: 604-12.
139. Song HJ, Kim YS, Han CH, Jang JY, Kim JH, Cheon YK, et al. [A Case of Complete Regression of Hepatocellular Carcinoma during Administration of COX-2 Inhibitor]. Korean J Hepatol 2006; 12: 449-54.
140. Dohmen K, Okabe H, Ishibashi H. Regression of hepatocellular carcinoma due to cyclooxygenase (COX)-2 inhibitor. Am J Gastroentetol 2006; 101: 2437-8.
141. Malka D, Pacault V, De Baere T, Ducreux M, Boige V. Antitumoral effect of celecoxib in hepatocellular carcinoma. J Clin Oncol 2005; 23: 4805-6.
142. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. Jama 2001; 286: 954-9.
143. Sharma JN, Jawad NM. Adverse effects of COX-2 inhibitors. Scientific WorldJournal 2005; 5: 629-45.
144. Jang TJ. Expression of proteins related to prostaglandin E2 biosynthesis is increased in human gastric cancer and during gastric carcinogenesis. Virchows Arch 2004; 445: 564-71.
145. Kamei D, Murakami M, Nakatani Y, Ishikawa Y, Ishii T, Kudo I. Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis. J Biol Chem 2003; 278: 19396-405.
146. Mehrotra S, Morimiya A, Agarwal B, Konger R, Badve S. Microsomal prostaglandin E2 sythase-1 in breast cancer: A potential target for therapy. J Pathol 2006; 208: 356-63.
147. Payner T, Leaver HA, Knapp B, Whittle IR, Trifan OC, Miller S, et al. Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E(2)-dependent activation of type II protein kinase A. Mol Cancer Ther 2006; 5: 1817-26.
148. Wang HW, Hsueh CT, Lin CF, Chou TY, Hsu WH, Wang LS, et al. Clinical implications of microsomal prostaglandin e synthase-1 overexpression in human non-small-cell lung cancer. Ann Surg Oncol 2006; 13: 1224-34.
149. Yoshimatsu K, Altorki NK, Golijanin D, Zhang F, Jakobsson PJ, Dannenberg AJ, et al. Inducible prostaglandin E synthase is over-expressed in non-small cell lung cancer. Clin Cancer Res 2001; 7: 2669-74.
150. Cohen EG, Almahmeed T, Du B, Golijanin D, Boyle JO, Soslow RA, et al. Microsomal prostaglandin E synthase-1 is overexpressed. in head and neck squamous cell carcinoma. Clin Cancer Res 2003; 9: 3425-30.
151. Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jakobsson PJ, DeLellis RA, et al. Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res 2001; 7: 3971-6.
152. Murakami M, Kudo I. Prostaglandin E synthase: A novel drug target for inflammation and cancer. Curr Pharm Des 2006; 12: 943-54.
153. Castellone MD, Teramoto H, Gutkind JS. Cyclooxygenase-2 and colorectal cancer chemoprevention: The beta-catenin connection. Cancer Res 2006; 66: 11085-8.
154. Chell S, Kadi A, Williams AC, Paraskeva C. Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer. Biochim Biophys Acta 2006; 1766: 104-19.
155. Chell S, Patsos HA, Qualtrough D, H-Zadeh AM, Hicks DJ, Kaidi A, et al. Prospects in NSAID-derived chemoprevention of colorectal cancer. Biochem Soc Trans 2005; 33: 667-71.
156. Fulton AM, Ma X, Kundu N. Targeting prostaglandin E EP receptors to inhibit metastasis. Cancer Res 2006; 66: 9794-7.
157. Hull MA, Ko SC, Hawcroft G. Prosotglandin EP receptors: Targets for treatment and prevention of colorectal cancer? Mol Cancer Ther 2004; 3: 1031-9.
158. Sinicrope FA. Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer. Mol Carcinog 2006; 45: 447-54.
159. Kobayashi T, Narumiya S. Function of prostanoid receptors: Studies on knockout mice. Prostaglandins Other Lipid Mediat 2002; 68-69: 557-73.
160. Kobayashi T, Narumiya S. Prostanoids in health and disease; lessons from receptor-knockout mice. Adv Exp Med Biol 2002; 507: 593-7.
161. Ushio, A, Takikawa Y, Lin SD, Miyarnoto Y, Suzuki K. Induction of Bcl-xL is a possible mechanism of anti-apoptotic effect by prostaglandin E2 EP4-receptor agonist in human hepatocellular carcinoma HepG2 cells. Hepatol Res 2004; 29: 173-9.
162. Han C, Demetris AJ, Liu Y, Shelhamer JH, Wu T. Transforming growth factor-beta (TGF-beta) activates cytosolic phospholipase A2alpha (cPLA2alpha)-mediated prostaglandin E2 (PGE)2/EP1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)/Smad signaling pathways in human liver cancer cells. A novel mechanism for subversion of TGF-beta-induced mitohihibition. J Biol Chem 2004; 279: 44344-54
163. de Vries EF. Imaging of cyclooxygenase-2 (COX-2) expression: Potential use in diagnosis and drug evaluation. Curr Pharm Des 2006; 12(30): 3847-56.
164. Hossain MA, Wakabayashi H, lzuishi K, Okano K, Yachida S, Maeta H. The role of prostaglandins in liver ischemia-reperfusion injury. Curr Pharm Des 2006; 12(23): 2935-51.
165. Ohno T. Autologous formalin-fixed tumor vaccine. Curr Pharm Des 2005; 11 (9): 1181-8.