Multifaceted roles of cyclooxygenase-2 in lung cancer

Achiwa, 1999, Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas, Clin. Cancer Res., 5, 1001 Alaoui-Jamali, 2003, The interface between ErbB and non-ErbB receptors in tumor invasion: clinical implications and opportunities for target discovery, Drug Resist. Update, 6, 95, 10.1016/S1368-7646(03)00024-4 Alleva, 1994, Tumor-induced regulation of suppressor macrophage nitric oxide and TNF-alpha production: role of tumor-derived IL-10, TGF-beta and prostaglandin E2, J. Immunol., 153, 1674, 10.4049/jimmunol.153.4.1674 Almand, 2000, Clinical significance of defective dendritic cell differentiation in cancer, Clin. Cancer Res., 6, 1755 Altorki, 2003, Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer, J. Clin. Oncol., 21, 2645, 10.1200/JCO.2003.07.127 Amano, 2003, Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth, J. Exp. Med., 197, 221, 10.1084/jem.20021408 Ambs, 1998, Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53, Br. J. Cancer, 78, 233, 10.1038/bjc.1998.470 Arenberg, 1996, Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice, J. Clin. Invest., 97, 2792, 10.1172/JCI118734 Banchereau, 1998, Dendritic cells and the control of immunity, Nature, 392, 245, 10.1038/32588 Bancroft, C.C., Chen, Z., Yeh, J., Sunwoo, J.B., Yeh, N.T., Jackson, S., Jackson, C., 2002. Effects of pharmacologic antagonists of epidermal growth factor receptor, P13K and MEK signal kinases on NF-kappa B and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines. Int. J. Cancer 99, 538–548. Bartolazzi, 1994, Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development, J. Exp. Med., 180, 53, 10.1084/jem.180.1.53 Berg, 2001, IL-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production, J. Immunol., 166, 2674, 10.4049/jimmunol.166.4.2674 Bianchi, 1996, IL-12 is both required and sufficient for initiating T cell reactivity to a class I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic cells, J. Immunol., 157, 1589, 10.4049/jimmunol.157.4.1589 Bissonnette, 2000, Mutational and nonmutational activation of p21ras in rat colonic azoxymethane-induced tumors: effects on mitogen-activated protein kinase, cyclooxygenase-2, and cyclin D1, Cancer Res., 60, 4602 Bouros, 2002, Association of malignancy with diseases causing interstitial pulmonary changes, Chest, 121, 1278, 10.1378/chest.121.4.1278 Brabender, 2002, Prognostic significance of cyclooxygenase 2 mRNA expression in non-small cell lung cancer, Ann. Surg., 235, 440, 10.1097/00000658-200203000-00017 Buchanan, 2003, Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor, J. Biol. Chem., 278, 35451, 10.1074/jbc.M302474200 Campa, 2004, Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer, Carcinogenesis, 25, 229, 10.1093/carcin/bgh008 Cao, 2000, Intracellular unesterified arachidonic acid signals apoptosis, Proc. Natl. Acad. Sci. U.S.A., 97, 11280, 10.1073/pnas.200367597 Carbone, 2002, Serum/plasma VEGF level changes with cyclooxygenase-2 (COX-2) inhibition in combined modality therapy in state III non-small cell lung cancer (NSCLC): preliminary results of a phase II trial (THO-0059), Proc. Am. Soc. Clin. Oncol., 21, 1270 Cassidy, 2002, Cyclooxygenase-2 induction by paclitaxel, docetaxel, and taxane analogues in human monocytes and murine macrophages: structure-activity relationships and their implications, Clin. Cancer Res., 8, 846 Catzavelos, 1999, Reduced expression of the cell cycle inhibitor p27Kip1 in non-small cell lung carcinoma: a prognostic factor independent of Ras, Cancer Res., 59, 684 Chambers, 2002, Metastasis: dissemination and growth of cancer cells in metastatic sites, Nat. Rev. Cancer, 2, 563, 10.1038/nrc865 Chan, 1999, Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck, Cancer Res., 59, 991 Chang, 2001, Cyclooxygenase-2 level and culture conditions influence NS398-induced apoptosis and caspase activation in lung cancer cells, Oncol. Rep., 8, 1321 Choy, 2003, Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance?, J. Natl. Cancer Inst., 95, 1440, 10.1093/jnci/djg058 Coffey, 1997, Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells, Proc. Natl. Acad. Sci. U.S.A., 94, 657, 10.1073/pnas.94.2.657 Colombo, 1996, Amount of interleukin 12 available at the tumor site is critical for tumor regression, Cancer Res., 56, 2531 Crew, 2000, A 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, 21, 69, 10.1093/carcin/21.1.69 D’Amico, 1999, A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers, J. Thorac. Cardiovasc. Surg., 117, 736, 10.1016/S0022-5223(99)70294-1 D’Andrea, 1993, Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells, J. Exp. Med., 178, 1041, 10.1084/jem.178.3.1041 Daniel, 1999, Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis, Cancer Res., 59, 4574 Dannenberg, 2003, Targeting cyclooxygenase-2 in human neoplasia: rationale and promise, Cancer Cell, 4, 431, 10.1016/S1535-6108(03)00310-6 Dannenberg, 2001, Inhibition of cyclooxygenase-2: an approach to preventing cancer of the upper aerodigestive tract, Ann. N.Y. Acad. Sci., 952, 109, 10.1111/j.1749-6632.2001.tb02731.x Dazzi, 1999, Prognostic and predictive value of intratumoral microvessel density in operable non-small-cell lung cancer, Lung Cancer, 24, 81, 10.1016/S0169-5002(99)00036-7 De Vita, 2000, Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients, Chest, 117, 365, 10.1378/chest.117.2.365 Dohadwala, 2002, Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion, J. Biol. Chem., 277, 50828, 10.1074/jbc.M210707200 Dohadwala, 2001, Non-small cell lung cancer cylooxygenase-2-dependent invasion is mediated by CD44, J. Biol. Chem., 276, 20809, 10.1074/jbc.C100140200 Duarte, 1998, Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer, J. Thorac. Cardiovasc. Surg., 115, 652, 10.1016/S0022-5223(98)70331-9 Dubinett, 2003, Cyclooxygenase-2 in lung cancer, Prog. Exp. Tumor Res., 37, 138, 10.1159/000071371 DuBois, 1996, G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2, Cancer Res., 56, 733 Dubois, 1998, Cyclooxygenase in biology and disease, FASEB J., 12, 1063, 10.1096/fasebj.12.12.1063 Dy, 2002, Novel targets for lung cancer therapy: part I, J. Clin. Oncol., 20, 2881, 10.1200/JCO.2002.11.145 Dy, 2002, Novel targets for lung cancer therapy: part II, J. Clin. Oncol., 20, 3016, 10.1200/JCO.2002.02.112 Elder, 1997, 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., 3, 1679 Eling, 1990, Prostaglandin H synthase and xenobiotic oxidation, Ann. Rev. Pharmacol. Toxicol., 30, 1, 10.1146/annurev.pa.30.040190.000245 Erickson, 1999, The effect of selective cyclooxygenase inhibitors on intestinal epithelial cell mitogenesis, J. Surg. Res., 81, 101, 10.1006/jsre.1998.5511 Ermert, 2003, Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors, Clin. Cancer Res., 9, 1604 Esposito, 1997, Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer, Cancer Res., 57, 3381 Ferreira, 2002, Apoptosis: target of cancer therapy, Clin. Cancer Res., 8, 2024 Folkman, 1995, Angiogenesis in cancer, vascular, rheumatoid and other disease, Nat. Med., 1, 27, 10.1038/nm0195-27 Folkman, 2001, Angiogenesis-dependent diseases, Semin. Oncol., 28, 536, 10.1016/S0093-7754(01)90021-1 Fong, 1999, Molecular pathogenesis of lung cancer, J. Thorac. Cardiovasc. Surg., 118, 1136, 10.1016/S0022-5223(99)70121-2 Fontanini, 1995, Microvessel count predicts metastatic disease and survival in non-small cell lung cancer, J. Pathol., 177, 57, 10.1002/path.1711770110 Frantz, 1995, The effect of sodium salicylate and aspirin on NF-kappa B, Science, 270, 2017, 10.1126/science.270.5244.2017 Fujita, 2000, Relationship between cyclooxygenase-2 expression and K-ras gene mutation in colorectal adenomas, J. Gastroenterol. Hepatol., 15, 1277 Gately, 2000, The contributions of cyclooxygenase-2 to tumor angiogenesis, Cancer Metastasis Rev., 19, 19, 10.1023/A:1026575610124 Giatromanolaki, 1996, Prognostic value of angiogenesis in operable non-small cell lung cancer, J. Pathol., 179, 80, 10.1002/(SICI)1096-9896(199605)179:1<80::AID-PATH547>3.0.CO;2-X Gilhooly, 1999, The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines, Int. J. Oncol., 15, 267 Grosch, 2001, COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib, FASEB J., 15, 2742, 10.1096/fj.01-0299fje Guddo, 1999, The expression of basic fibroblast growth factor (bFGF) in tumor-associated stromal cells and vessels is inversely correlated with non-small cell lung cancer progression, Hum. Pathol., 30, 788, 10.1016/S0046-8177(99)90139-9 Hagenbaugh, 1997, Altered immune responses in IL-10 transgenic mice, J. Exp. Med., 185, 2101, 10.1084/jem.185.12.2101 Halak, 1999, Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site, Cancer Res., 59, 911 Hanahan, 2000, The hallmarks of cancer, Cell, 100, 57, 10.1016/S0092-8674(00)81683-9 Handel-Fernandez, 1997, Down-regulation of IL-12, not a shift from a T helper-1 to a T helper-2 phenotype, is responsible for impaired IFN-g production in mammary tumor-bearing mice, J. Immunol., 158, 280, 10.4049/jimmunol.158.1.280 Hara, 1997, Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines, Jpn. J. Cancer Res., 88, 600, 10.1111/j.1349-7006.1997.tb00424.x Harizi, 2002, Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions, J. Immunol., 168, 2255, 10.4049/jimmunol.168.5.2255 Harpole, 1996, Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer, Ann. Thorac. Surg., 61, 1470, 10.1016/0003-4975(96)00104-X Hasturk, 2002, Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma, Cancer, 94, 1023, 10.1002/cncr.10262 Hatanaka, 2000, Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer, Ann. Oncol., 11, 815, 10.1023/A:1008375208574 Hatanaka, 2001, Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer, Clin. Cancer Res., 7, 1287 Hawk, 2002, COX-2 in cancer—a player that’s defining the rules, J. Natl. Cancer Inst., 94, 545, 10.1093/jnci/94.8.545 He, 1999, PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs, Cell, 99, 335, 10.1016/S0092-8674(00)81664-5 Heasley, 1997, Induction of cytosolic phospholipase A2 by oncogenic Ras in human non-small cell lung cancer, J. Biol. Chem., 272, 14501, 10.1074/jbc.272.23.14501 Hennekens, 1996, Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease, N. Engl. J. Med., 334, 1145, 10.1056/NEJM199605023341801 Herschman, 1996, Review: prostaglandin synthase 2, Biochim. Biophys. Acta, 1299, 125, 10.1016/0005-2760(95)00194-8 Heuze-Vourc’h, 2003, Abnormal interleukin 10Ralpha expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells, Cancer Res., 63, 766 Hida, 2002, Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents, Clin. Cancer Res., 8, 2443 Hida, 2000, Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines, Clin. Cancer Res., 6, 2006 Hida, 1998, Non-small cell lung cancer cyclooxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs, Anticancer Res., 18, 775 Hida, 1998, Increased expression of cycloxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas, Cancer Res., 58, 3761 Hillerdal, 1997, Asbestos, asbestosis, pleural plaques and lung cancer, Scand. J. Work Environ. Health, 23, 93, 10.5271/sjweh.186 Hirsch, 2001, Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology, Clin. Cancer Res., 7, 5 Hirsch, 2002, Expression of target molecules in lung cancer: challenge for a new treatment paradigm, Semin. Oncol., 29, 2, 10.1053/sonc.2002.34265 Ho, 2002, Arsenite pretreatment attenuates benzo[a]pyrene cytotoxicity in a human lung adenocarcinoma cell line by decreasing cyclooxygenase-2 levels, J. Toxicol. Environ. Health A, 65, 245, 10.1080/15287390252800846 Hosomi, 2000, Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung, Lung Cancer, 30, 73, 10.1016/S0169-5002(00)00132-X Hsu, 2000, The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2, J. Biol. Chem., 275, 11397, 10.1074/jbc.275.15.11397 Hsueh, 2000, Selective inhibition of cyclooxygenase-2 enhances mitomycin-C-induced apoptosis, Cancer Chemother. Pharmacol., 45, 389, 10.1007/s002800051007 Huang, 1994, Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens, Science, 264, 961, 10.1126/science.7513904 Huang, 1995, Human non-small cell lung cancer cells express a type 2 cytokine pattern, Cancer Res., 55, 3847 Huang, 1997, Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice, J. Biol. Chem., 272, 26325, 10.1074/jbc.272.42.26325 Huang, 1996, Non-small cell lung cancer-derived soluble mediators and prostaglandin E2 enhance peripheral blood lymphocyte IL-10 transcription and protein production, J. Immunol., 157, 5512, 10.4049/jimmunol.157.12.5512 Huang, 1998, 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 Hung, 2000, Induction of p27(KIP1) as a mechanism underlying NS398-induced growth inhibition in human lung cancer cells, Mol. Pharmacol., 58, 1398, 10.1124/mol.58.6.1398 Hwang, 2002, National Cancer Institute workshop on chemopreventive properties of nonsteroidal anti-inflammatory drugs: role of COX-dependent and -independent mechanisms, Neoplasia, 4, 91, 10.1038/sj.neo.7900226 Jemal, 2003, Cancer statistics, CA Cancer J. Clin., 53, 5, 10.3322/canjclin.53.1.5 Johnson, 2003, Cyclooxygenase-2 (COX-2) inhibition in non-small cell lung cancer (NSCLC): preliminary results of a phase II trial, Proc. Am. Soc. Clin. Oncol., 22, 640 Kalinski, 1997, Dendritic cells, obtained from peripheral blood precursors in the presence of PGE2, promote Th2 responses, Adv. Exp. Med. Biol., 417, 363, 10.1007/978-1-4757-9966-8_59 Kelley, 1997, Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells, Carcinogenesis, 18, 795, 10.1093/carcin/18.4.795 Khuri, 2001, Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer, Clin. Cancer Res., 7, 861 Kim, 2004, Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival, Clin. Cancer Res., 10, 1366, 10.1158/1078-0432.CCR-0497-03 Kim, 2003, Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer, Lung Cancer, 42, 163, 10.1016/S0169-5002(03)00290-3 Kim, 1995, IL-10 production in cutaneous basal and squamous cell carcinomas: a mechanism for evading the local T cell immune response, J. Immunol., 155, 2240, 10.4049/jimmunol.155.4.2240 Kinoshita, 1999, Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells, Biochim. Biophys. Acta, 1438, 120, 10.1016/S1388-1981(99)00034-7 Kinzler, 1998, Landscaping the cancer terrain, Science, 280, 1036, 10.1126/science.280.5366.1036 Kishi, 2000, Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor, Cancer Res., 60, 1326 Koki, 1999, Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy, Expert Opin. Investig. Drugs, 8, 1623, 10.1517/13543784.8.10.1623 Komaki, 2004, Improvement strategies for molecular targeting: cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer, Semin. Oncol., 31, 47, 10.1053/j.seminoncol.2003.12.014 Konishi, 2000, The K-ras gene regulates vascular endothelial growth factor gene expression in non-small cell lung cancers, Int. J. Oncol., 16, 501 Koukourakis, 1997, Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer, Br. J. Cancer, 75, 477, 10.1038/bjc.1997.83 Kozaki, 2001, 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, 10.1038/sj.onc.1204561 Krysan, 2004, COX-2-dependent stabilization of survivin in non-small cell lung cancer, FASEB J., 18, 206, 10.1096/fj.03-0369fje Krysan, 2004, PGE2 activates MAPk/Erk pathway in non-small cell lung cancer cells in an EGF receptor-independent manner, Proc. Am. Assoc. Cancer Res., 45, 907 Lamb, 1997, AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44, Mol. Cell Biol., 17, 963, 10.1128/MCB.17.2.963 Leahy, 2000, Role of cyclooxygenases in angiogenesis, Curr. Med. Chem, 7, 1163, 10.2174/0929867003374336 Leahy, 2002, Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo, Cancer Res., 62, 625 Liao, 2003, 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, 216 Lin, 2001, Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway, J. Biol. Chem., 276, 48997, 10.1074/jbc.M107829200 Lippman, 2001, Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer, J. Natl. Cancer Inst., 93, 605, 10.1093/jnci/93.8.605 Liu, 2000, Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo, J. Urol., 164, 820, 10.1016/S0022-5347(05)67321-1 Liu, 1998, NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells, Cancer Res., 58, 4245 Macchiarini, 1992, Relation of neovascularisation to metastasis of non-small-cell lung cancer, Lancet, 340, 145, 10.1016/0140-6736(92)93217-B Malumbres, 2001, To cycle or not to cycle: a critical decision in cancer, Nat. Rev. Cancer, 1, 222, 10.1038/35106065 Mao, 2003, Celecoxib modulates the capacity for prostaglandin E2 and interleukin-10 production in alveolar macrophages from active smokers, Clin. Cancer Res., 9, 5835 Marrogi, 2000, Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma, Clin. Cancer Res., 6, 4739 Masferrer, 2000, Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors, Cancer Res., 60, 1306 Milas, 2001, Cyclooxygenase-2 (COX-2) enzyme inhibitors as potential enhancers of tumor radioresponse, Semin. Radiat. Oncol., 11, 290, 10.1053/srao.2001.26018 Milas, 1990, Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence, Cancer Res., 50, 4473 Milas, 1991, Antitumour effects of indomethacin alone and in combination with radiotherapy: role of inhibition of tumour angiogenesis, Int. J. Radiat. Biol., 60, 65, 10.1080/09553009114551561 Milas, 1999, Enhancement of tumor response to gamma-radiation by an inhibitor of cyclooxygenase-2 enzyme, J. Natl. Cancer Inst., 91, 1501, 10.1093/jnci/91.17.1501 Molina-Holgado, 2002, Theiler’s virus infection induces the expression of cyclooxygenase-2 in murine astrocytes: inhibition by the anti-inflammatory cytokines interleukin-4 and interleukin-10, Neurosci. Lett., 324, 237, 10.1016/S0304-3940(02)00209-4 Moore, 2001, Interleukin-10 and the interleukin-10 receptor, Annu. Rev. Immunol., 19, 683, 10.1146/annurev.immunol.19.1.683 Moos, 1999, Effect of taxol and taxotere on gene expression in macrophages: induction of the prostaglandin H synthase-2 isoenzyme, J. Immunol., 162, 467, 10.4049/jimmunol.162.1.467 Murata, 1999, Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma, Am. J. Gastroenterol., 94, 451, 10.1111/j.1572-0241.1999.876_e.x Naruke, 2001, Interleukin-10 expression is correlated with growth fraction in human non-small cell lung cancer xenografts, Int. J. Oncol., 18, 1213 Neuner, 2001, Cytokine secretion: clinical relevance of immunosuppression in non-small cell lung cancer, Lung Cancer, 34, 579, 10.1016/S0169-5002(01)00350-6 Niki, 2002, Frequent co-localization of Cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas, Am. J. Pathol., 160, 1129, 10.1016/S0002-9440(10)64933-4 Ochiai, 1999, Cyclooxygenase-2 (COX-2) mRNA expression levels in normal lung tissues and non-small cell lung cancers, Jpn. J. Cancer Res., 90, 1338, 10.1111/j.1349-7006.1999.tb00717.x Ohta, 1999, VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours, Br. J. Cancer, 81, 54, 10.1038/sj.bjc.6690650 Omenn, G., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L, Valanis, B., Williams, J.H., Barnhart, S., Hammar, S., 1996. Effects of a combination of beta carotene and Vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med, 1150–1155. Ono, 2002, Epidermal growth factor receptor gene amplification is correlated with laminin-5 gamma2 chain expression in oral squamous cell carcinoma cell lines, Cancer Lett., 175, 197, 10.1016/S0304-3835(01)00682-6 Pai, 2002, Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy, Nat. Med., 8, 289, 10.1038/nm0302-289 Pan, 2001, Non-steroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 expression via repression of transcription in lung cancer cells, FEBS Lett., 508, 365, 10.1016/S0014-5793(01)03118-0 Petersen, 2000, Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor, Clin. Cancer Res., 6, 2513 Pisters, 2000, Induction chemotherapy before surgery for early-stage lung cancer: a novel approach. Bimodality lung oncology team, J. Thorac. Cardiovasc. Surg., 119, 429, 10.1016/S0022-5223(00)70120-6 Pold, 2002, Microarray identifies cyclooxygenase-2-dependent modulation of insulin-like growth factor binding protein-3 in non-small cell lung cancer cells, Chest, 121, 29S, 10.1378/chest.121.3_suppl.29S Pold, 2004, Cyclooxygenase-2 dependent expression of angiogenic CXC chemokine, ENA-78/CXC5 and IL-8/CXCL8, in human NSCLC, Cancer Res., 64, 1853, 10.1158/0008-5472.CAN-03-3262 Pomini, 1999, Interleukin-10 modifies the effects of interleukin-1beta and tumor necrosis factor-alpha on the activity and expression of prostaglandin H synthase-2 and the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase in cultured term human villous trophoblast and chorion trophoblast cells, J. Clin. Endocrinol. Metab., 84, 4645, 10.1210/jc.84.12.4645 Pyke, 1994, The gamma 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers, Am. J. Pathol., 145, 782 Pyke, 1995, Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas, Cancer Res., 55, 4132 Pyo, H., Choy, H., Amorino, G.P., Kim, J.P., Cao, Q., Hercules, S.K., DuBois, R.N., 2001. 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. Qin, 1997, Adenovirus-mediated gene transfer of viral interleukin-10 inhibits the immune response to both alloantigen and adenoviral antigen, Hum. Gene Ther., 8, 1365, 10.1089/hum.1997.8.11-1365 Ravi, 2000, Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha, Genes Dev., 14, 34, 10.1101/gad.14.1.34 Rioux, 1998, Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398, Cancer Res., 58, 5354 Roth, 1993, Human pulmonary macrophages utilize prostaglandins and transforming growth factor beta1 to suppress lymphocyte activation, J. Leukoc. Biol., 53, 366, 10.1002/jlb.53.4.366 Sanchez-Alcazar, 2003, Cyclooxygenase (COX) inhibitors induce apoptosis in non-small cell lung cancer through cyclooxygenase independent pathways, Lung Cancer, 40, 33, 10.1016/S0169-5002(02)00530-5 Sawaoka, 1998, Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice, Am. J. Physiol., 274, G1061 Schreinemachers, 1994, Aspirin use and lung, colon, and breast cancer incidence in a prospective study, Epidemiology, 5, 138, 10.1097/00001648-199403000-00003 Seiter, 1993, Prevention of tumor metastasis formation by anti-variant CD44, J. Exp. Med., 177, 443, 10.1084/jem.177.2.443 Shah, 2002, Pronounced radiosensitization of cultured human cancer cells by COX inhibitor under acidic microenvironment, Int. J. Radiat. Oncol. Biol. Phys., 53, 1314, 10.1016/S0360-3016(02)02889-4 Shamma, 2000, Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus, Clin. Cancer Res., 6, 1229 Shankavaram, 2001, Monocyte membrane type 1-matrix metalloproteinase. Prostaglandin-dependent regulation and role in metalloproteinase-2 activation, J. Biol. Chem., 276, 19027, 10.1074/jbc.M009562200 Sharma, 1999, T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function, J. Immunol., 163, 5020, 10.4049/jimmunol.163.9.5020 Sharma, 2003, Tumor cyclooxygenase 2-dependent suppression of dendritic cell function, Clin. Cancer Res., 9, 961 Sheng, 2000, Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA, J. Biol. Chem., 275, 6628, 10.1074/jbc.275.9.6628 Sheng, 1998, Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells, Cancer Res., 58, 362 Shiff, 1995, Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells, J. Clin. Invest., 96, 491, 10.1172/JCI118060 Shirane, 1999, Down-regulation of p27(Kip1) by two mechanisms, ubiquitin-mediated degradation and proteolytic processing, J. Biol. Chem., 274, 13886, 10.1074/jbc.274.20.13886 Skyldberg, 1999, Laminin-5 as a marker of invasiveness in cervical lesions, J. Natl. Cancer Inst., 91, 1882, 10.1093/jnci/91.21.1882 Smith, 2000, Cyclooxygenases: structural, cellular, and molecular biology, Annu. Rev. Biochem., 69, 145, 10.1146/annurev.biochem.69.1.145 Sombroek, 2002, Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation, J. Immunol., 168, 4333, 10.4049/jimmunol.168.9.4333 Song, 2002, Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells, J. Natl. Cancer Inst., 94, 585, 10.1093/jnci/94.8.585 Sordat, 1998, Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia, J. Pathol., 185, 44, 10.1002/(SICI)1096-9896(199805)185:1<44::AID-PATH46>3.0.CO;2-A Soslow, 2000, COX-2 is expressed in human pulmonary, colonic, and mammary tumors, Cancer, 89, 2637, 10.1002/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B Stacker, 2001, VEGF-D promotes the metastatic spread of tumor cells via the lymphatics, Nat. Med., 7, 186, 10.1038/84635 Stolina, 2000, Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis, J. Immunol., 164, 361, 10.4049/jimmunol.164.1.361 Su, 2004, Cyclooxygenase-2 induces EP(1)- and HER-2/Neu-dependent vascular endothelial growth factor-C upregulation: a novel mechanism of lymphangiogenesis in lung adenocarcinoma, Cancer Res., 64, 554, 10.1158/0008-5472.CAN-03-1301 Subbaramaiah, 1999, Inhibition of cyclooxygenase-2 gene expression by p53, J. Biol. Chem., 274, 10911, 10.1074/jbc.274.16.10911 Subbaramaiah, 2000, Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways, J. Biol. Chem., 275, 14838, 10.1074/jbc.275.20.14838 Subbaramaiah, 2003, Regulation of cyclooxygenase-2 mRNA stability by taxanes: evidence for involvement of p38, MAPKAPK-2, and HuR, J. Biol. Chem., 278, 37637, 10.1074/jbc.M301481200 Subbaramaiah, 1996, Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells, Cancer Res., 56, 4424 Swisher, 1993, Pulmonary macrophages suppress the proliferation and cytotoxicity of tumor-infiltrating lymphocytes, Am. J. Resp. Cell Mol. Biol., 8, 486, 10.1165/ajrcmb/8.5.486 Thun, 2002, Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues, J. Natl. Cancer Inst., 94, 252, 10.1093/jnci/94.4.252 Tsujii, 1995, Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase-2, Cell, 83, 493, 10.1016/0092-8674(95)90127-2 Tsujii, 1997, Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential, Proc. Natl. Acad. Sci. U.S.A., 94, 3336, 10.1073/pnas.94.7.3336 Tsujii, 1998, Cyclooxygenase regulates angiogenesis induced by colon cancer cells, Cell, 93, 705, 10.1016/S0092-8674(00)81433-6 Uefuji, 2000, Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer, Clin. Cancer Res., 6, 135 Urosevic, 2001, Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production, Am. J. Pathol., 159, 817, 10.1016/S0002-9440(10)61756-7 Wardlaw, 2000, Cyclooxygenase-2 expression in abundant in alveolar type II cells in lung cancer-sensitive mouse strains and in premalignant lesions, Carcinogenesis, 21, 1371, 10.1093/carcin/21.7.1371 Wardlaw, 2002, Transcriptional regulation of basal cyclooxygenase-2 expression in murine lung tumor-derived cell lines by CCAAT/Enhancer-binding protein and activating transcription factor/cAMP response element-binding protein, Mol. Pharmacol., 62, 326, 10.1124/mol.62.2.326 Watkins, 1999, Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer, Eur. Respir. J., 14, 412, 10.1183/09031936.99.14241299 West, 2002, Activation of the PI3K/Akt pathway and chemotherapeutic resistance, Drug Resist. Update, 5, 234, 10.1016/S1368-7646(02)00120-6 West, 2002, Cyclooxygenase-2 (COX-2) overexpression by immunohistochemistry (IHC) is associated with more aggressive biologic behavior of non-small cell lung cancer (NSCLC) tumors, Proc. Am. Soc. Clin. Oncol., 21, 1235 Wick, 2002, Peroxisome proliferator-activated receptor-gamma is a target of nonsteroidal anti-inflammatory drugs mediating cyclooxygenase-independent inhibition of lung cancer cell growth, Mol. Pharmacol., 62, 1207, 10.1124/mol.62.5.1207 Wiese, 2001, Carcinogen substrate specificity of human COX-1 and COX-2, Carcinogenesis, 22, 5, 10.1093/carcin/22.1.5 Wikstrom, 1998, Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer, Prostate, 37, 19, 10.1002/(SICI)1097-0045(19980915)37:1<19::AID-PROS4>3.0.CO;2-3 Williams, 2000, Host cyclooxygenase-2 modulates carcinoma growth, J. Clin. Invest., 105, 1589, 10.1172/JCI9621 Wolff, 1998, Expression of cyclooxygenase-2 in human lung carcinoma, Cancer Res., 58, 4997 Wu, C.-Y., Demeure, C., Kiniwa, M., Gately, M., Delespesse, G., 1993. IL-12 induces the production of IFN-g by neonatal human CD4 T cells. J. Immunol. 151, 1938–1949. Xu, 2002, COX-2 inhibitors in cancer treatment and prevention, a recent development, Anti-Cancer Drugs, 13, 127, 10.1097/00001813-200202000-00003 Yang, 2003, Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor, J. Clin. Invest., 111, 727, 10.1172/JCI16492 Yao, 2000, Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs’ chemopreventive efficacies in mouse lung tumorigenesis, Exp. Lung Res., 26, 731, 10.1080/01902140150216783 Yatabe, 1998, p27KIP1 in human lung cancers: differential changes in small cell and non-small cell carcinomas, Cancer Res., 58, 1042 Yip-Schneider, 2000, Cyclooxygenase-2 expression in human pancreatic adenocarcinomas, Carcinogenesis, 21, 139, 10.1093/carcin/21.2.139 Yu, 1999, Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion, Genes Dev., 13, 35, 10.1101/gad.13.1.35 Yu, 2000, Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis, Genes Dev., 14, 163, 10.1101/gad.14.2.163