Unresolved issues in the role of cyclooxygenase-2 in normal physiologic processes and disease

Archives of Internal Medicine

Volumn 160, Issue 7, 2000, Pages 913-920

  Lipsky, Peter E ^a   Brooks, Peter ^b   Crofford, Leslie J ^c   DuBois, Raymond ^d   Graham, David ^e   Simon, Lee S ^f   Van De Putte, Leo B A ^g   Abramson, Steven B ^h  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF QUEENSLAND   (Australia)

^c UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^e MICHAEL E DEBAKEY VETERANS AFFAIRS MEDICAL CENTER   (United States)

^f HARVARD MEDICAL SCHOOL   (United States)

^g RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^h NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTACYCLIN; ROFECOXIB; THROMBOXANE A2;

ANTIINFLAMMATORY ACTIVITY; ARTHRITIS; BRAIN FUNCTION; ENDOTHELIUM CELL; ENZYME INHIBITION; GASTROINTESTINAL TRACT FUNCTION; HUMAN; KIDNEY FUNCTION; NERVE FUNCTION; OSTEOARTHRITIS; OVARY FUNCTION; PAIN; PRIORITY JOURNAL; PROSTAGLANDIN SYNTHESIS INHIBITION; REVIEW; RHEUMATOID ARTHRITIS; THROMBOSIS; UTERUS FUNCTION;

EID: 0034630270     PISSN: 00039926     EISSN: None     Source Type: Journal    
DOI: 10.1001/archinte.160.7.913     Document Type: Review

References (120)

1. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J. 1998;1063-1073.
2. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for the aspirin-like drugs. Nature. 1971;231:232-235.
3. Davies P, Bailey PJ, Goldenberg MM, Ford-Hutchinson AW. The role of arachidonic oxygenation products in pain and inflammation. Annu Rev Immunol. 1984;2:335-357.
4. Vane JR, Botting RM. Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997; 26:2-10.
5. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta. 1996;1299:125-140.
6. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996;271:33157-33160.
7. Jouzeau J-Y, Terlain B, Abid A, Nédélec E, Netter P. Cydo-oxygenase isoenzymes. Drugs. 1997; 53:563-582.
8. Masferrer JL, Isakson PC, Seibert K. Cyclooxygenase-2 inhibitors. Gastroenterol Clin North Am. 1996;25:363-372.
9. van Ryn J, Pairet M. Selective cyclooxygenase-2 inhibitors: pharmacology, clinical effects and therapeutic potential. Exp Opin Invest Drugs. 1997;6:609-614.
10. Simon LS, Lanza FL, Lipsky PE, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor. Arthritis Rheum. 1998;1:1591-1602.
11. Enrich E, Schnitzer T, Kivitz A, et al. MK-966, a highly selective cox-2 inhibitor, was effective in the treatment of osteoarthritis (OA) of the knee and hip in a 6-week placebo controlled study. Arthritis Rheum. 1997;40(supp):S85.
12. 2 production. J Pharmacol Exp Ther. 1997;283:1069-1075.
13. 2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo. J Exp Med. 1996;184:883-891.
14. Davies N. Toxicity of nonsteroidal anti-inflammatory drugs in the large intestine. Dis Colon Rectum. 1995;38:1311-1321.
15. Gutthann SP. Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med. 1996;156:2433-2439.
16. Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104:413-421.
17. Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and -2. Adv Immunol. 1996; 62:167-215.
18. García Rodríguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343:769-772.
19. García Rodríguez LA, Cattaruzzi C, Troncon MG, Agostinis L. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Arch Intern Med. 1998;158: 33-39.
20. Singh G, Ramey DR, Morfeld D. Shi H, Hatoum HT, Fries JF. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. Arch Intern Med. 1996;156:1530-1536.
21. Scheiman JM. NSAIDs, gastrointestinal injury, and cytoprotection. Gastroenterol Clin North Am. 1996;25:279-299.
22. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to the use of nonsteroidal antiinflammatory drugs: a meta-analysis. Ann Intern Med. 1991;115:787-796.
23. Langman MJS, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343:1075-1078.
24. Raz A, Wyche A, Siegel N, Needleman P. Regulation of fibroblast cyclooxygenase synthesis by interleukin-1. J Biol Chem. 1988;263:3022-3028.
25. Raz A, Wyche A, Siegel N, Needleman P. Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases. Proc Natl Acad Sci U S A. 1989;86:1657-1661.
26. 2 synthase (cyclooxygenase) in human monocytes. J Clin Invest. 1990;86:1375-1379.
27. Kraemer SA, Meade SA, Dewitt DL. Arch Biochem Biophys. 1992;293:391-400.
28. Kujubu DA, Fletcher BS, Varnum BC, Lim FW, Herschman HR. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/ cyclooxygenase homologue. J Biol Chem. 1991; 266:12866-12872.
29. Jones DA, Carlton DD, McIntyre TM, Zimmerman GA, Prescott SM. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expiation in response to cytokines. J Biol Chem. 1993;268:9049-9054.
30. Muakami M, Matsumoto R, Austen KF, Arm JP. Prostaglandin endoperoxide synthase-1 and -2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells. J Biol Chem. 1994;269:22269-22275.
31. Kawata R, Reddy ST, Wolner B, Herschman HR. Prostaglandin synthase I and prostaglandin synthase II both participate in activation-induced prostaglandin D2 production in mast cell. J Immunol. 1995;155:818-825.
32. Karim S, Habib A, Levy-Toledano S, Maclouf J. Cyclooxygenases-1 and -2 of endothelial cells utilize exogenous or endogenous arachidonic acid for transcellular production of thromboxane. J Biol Chem. 1996;271:12042-12048.
33. Kurumbail RG, Stevens AM, et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996;384: 644-648.
34. Luong C, Miller A, Barnett J, Chow J, Ramesha C, Browner MF. Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2. Nat Struct Biol. 1996;3:927-933.
35. Picot D, Loll PJ, Garavito M. The x-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature. 1994;367:243-249.
36. Crofford L. COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol. 1997;24:15-19.
37. Zambraski EJ. The effects of nonsteroidal anti-inflammatory drugs on renal function: experimental studies in animals. Semin Nephrol. 1995; 15:205-213.
38. Breyer MD, Jacobson HR, Breyer RM. Functional and molecular aspects of renal prostaglandin receptors. J Am Soc Nephrol. 1996;7: 8-17.
39. Burch JW, Stanford N, Majerus PW. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest. 1978;61:314-319.
40. Crofford LJ. Expression and regulation of cyclooxygenase-2 in synovial tissues of arthritic patients. In: Bazan N, Botting J, Vane J, eds. New Targets in Inflammation: Inhibitors of COX-2 or Adhesion Molecules. Boston, Mass: Kluwer Academic Publishers, William Harvey Press; 1996: 83-91.
41. Kang RY, Freire-Moar J, Sigal E, Chu C-Q. Expression of cyclooxygenase-2 in human and and animal models of rheumatoid arthritis. Br J Rheum. 1996;35:711-718.
42. Crofford LJ, Wilder RL, Ristimaki AD, Remmers EF, Epps HR, Hla T. Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: effects of interleukin-1β, phorbol ester, and corticosteroids. J Clin Invest. 1994;93:1095-1101.
43. Anderson GD, Hauser SD, Bremer ME, McGarity KL, Isakson PC, Gregory SA. Selective inhibition of cyclooxygenase-2 reverses inflammation and expression of COX-2 and IL-6 in rat adjuvant arthritis. J Clin Invest. 1998;97:2672-2679.
44. Brannon TS, North AJ, Wells LB, Shaul PW. Prostacyclin synthesis in ovine pulmonary artery is developmentally regulated by changes in cyclooxygenase-1 gene expression. J Clin Invest. 1994;93:2230-2235.
45. Hla T, Maciag T. Cyclooxygenase gene expression is down-regulated by heparin-binding (acid fibroblast) growth factor-1 in human endothelial cells. J Biol Chem. 1991;266:24059-24063.
46. Samet JM, Fasano MB, Fonteh AN, Chilton FH. Selective induction of prostaglandin G/H synthase I by stem cell factor and dexamethasone in mast cells. J Biol Chem. 1995;270:8044-8049.
47. Cohn SM, Schloemann S, Tessner T, Seibert K, Stenson WF. Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1. J Clin Invest. 1997;99:1367-1379.
48. Langenbach R, Morham SG, Tirano HF, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. 1995;83:483-492.
49. Harris RC, McKanna JA, Akai Y, Jacobson HR, Dubois RN, Breyer MD. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest. 1994; 94:2504-2510.
50. Guan Y, Chang M, Cho W, et al. Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells. Am J Physiol. 1997;273:F18-F26.
51. Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993;11:371-386.
52. Kaufmann WE, Worley P, Pegg J, Bremer M, Isakson PC. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Natl Acad Sci U S A. 1996;93:2317-2321.
53. Tocco G, Freire-Moar J, Schreiber SS, Sakhi SH, Aisen PS, Pasinetti GM. Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease. Exp Neurol. 1997;144:339-349.
54. Miettinen S, Fusco F, Yrjanheikki J, et al. Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2. Proc Natl Acad Sci U S A. 1997; 94:6500-6505.
55. Lim H, Paria B, Das SK, et al. Multiple female reproductive failures in cyclooxygenase-2 deficient mice. Cell. 1997;91:197-208.
56. Narko K, Ritvos O, Ristimaki A. Induction of cyclooxygenase-2 and prostaglandin F2 alpha receptor expression by interleukin-1 beta in cultured human granulosa-luteal cells. Endocrinology. 1997;138:3638-3644.
57. Chakraborty I, Das SK, Wang J, Dey SK. Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the periimplantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids. J Mol Endocrinol. 1996;16:107-122.
58. Morris JK, Richards JS. An E-box region within the prostaglandin endoperoxide synthase-2 (PGS-2) promoter is required for transcription in rat ovarian granulosa cells. J Biol Chem. 1996; 271:16633-16643.
59. Chakraborty I, Das S, Wang J, Dey SK. Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the periimplantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids. J Mol Endocrinol. 1996;16:107-122.
60. Yang ZM, Das S, Wang J, Sugimoto Y, Ichikawa A, Dey SK. Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes. Biol Reprod. 1997;56: 368-379.
61. Bergmann P, Schoutens A. Prostaglandins and bone. Bone. 1995;16:485-488.
62. Pilbeam CC, Fall PM, Alander CB, Raisz LG. Differential effects of nonsteroidal anti-inflammatory drugs on constitutive and inducible prostaglandin G/H synthase in cultured bone cells. J Bone Miner Res. 1997;12:1198-1203.
63. Tai H, Miyaura C, Pilbeam CC, et al. Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation. Endocrinology. 1997;138: 2372-2379.
64. Sato T, Morita I, Sakaguchi K, Nakahama K, Murota S. Involvement of cyclooxygenase-2 in bone loss induced by interleukin-1 beta. Adv Prostaglandin Thromboxane Leukotriene Res. 1995;23:445-447.
65. Onoe Y, Miyaura C, Kaminakayashiki T, et al. IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts. J Immunol. 1996;156:758-764.
66. Amin AR, Attur M, Patel RN, et al. Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. J Clin Invest. 1997; 99:1231-1237.
67. Palmer BF, Henrich WL. Clinical acute renal failure with nonsteroidal anti-inflammatory drugs. Semin Nephrol. 1995;15:214-227.
68. Dinchuk JE, Car BD, Focht RJ, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature. 1995;378:406-409.
69. Morham SG, Langenbach R, Loftin CD, Prostaglandin synthase-2 gene disruption causes severe renal pathology in the mouse. Cell. 1995; 83:473-482.
70. Zhang M-Z, Wang J-L, Cheng H-F, Harris RC, McKanna JA. Cyclooxygenase-2 in rat nephron development. Am J Physiol. 1997:273;F994-F1002.
71. Komhoff M, Grone JJ, Klein T. Seyerth HW, Nusing RM. Localization of cyclooxygenase-1 and cyclooxygenase-2 in adult and fetal human kidney: implication for renal function. Am J Physiol. 1997;271:F460-F468.
72. Khan KNM, Venturini CM, Bunch RT, et al. Inter-species differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity. Toxicol Path. 1998;27:612-620.
73. Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of specific inhibition of cyclooxygenase 2 on sodium balance, hemodynamics and vasoactive eicosanoids. J Pharm Exp Ther. 1999; 289:735-741.
74. Kargman S, Charleson S, Cartwright M, et al. Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey and human gastrointestinal tracts. Gastroenterology. 1996;111: 445-454.
75. Schafter AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35:209-219.
76. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994;330:1237-1294.
77. Mizuno H, Sakamoto C, Matsuda K, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology. 1997;112:387-397.
78. Eckmann L, Stenson WF, Savidge TC, et al. Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria: bacterial entry induces epithelial prostaglandin H synthase-2 expression and prostaglandin E2 and F2a production. J Clin Invest. 1997;100:296-269.
79. Gianella RA, Formal SB, Dammin GJ, Collins H. Pathogenesis of salmonellosis: studies of fluid secretion, mucosal invasion, and morphologic reactions in the rabbit ileum. J Clin Invest. 1973; 52:441-453.
80. Wallace JL, Keenan CM, Gale D, Shoupe TS. Exacerbation of experimental colitis by nonsteroidal antiinflammatory drugs is not related to elevated leukotriene B4 synthesis. Gastroenterology. 1992;102:18-27.
81. Cao C, Matsumura K, Yamagata K, Watanabe Y. Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. Am J Physiol. 1997;272:R1712-R1725.
82. Matsumura K, Cao C, Watanabe Y. Possible role of cyclooxygenase-2 in the brain vasculature in febrile response. Ann N Y Acad Sci. 1997;813: 302-306.
83. Cao C, Matsumura K, Watanabe Y. Induction of cyclooxygenase-2 in the brain by cytokines. Ann N Y Acad Sci. 1997;813:307-309.
84. Taniguchi Y, Yokoyama K, Inui K, Deguchi Y, Furukawa K, Noda K. Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of nimesulide. Eur J Pharmacol. 1997;330:221-229.
85. -/- mice. Brain Res. 1999;825:86-94.
86. Kaufmann WE, Worley P, Taylor CV, Bremer M, Isakson PC. Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome. Brain Dev. 1997;19:25-34.
87. Saag KG, Rubenstein LM, Chrischilles EA, Wallace RB. Nonsteroidal antiinflammatory drugs and cognitive decline in the elderly. J Rheumatol. 1995;22:2142-2147.
88. Bauer MK, Lieb K, Schulze-Osthoff K, et al. Expression and regulation of cyclooxygenase-2 in rat microglia. Eur J Biochem. 1997;243:726-731.
89. Sugimoto Y, Yamasaki A, Segi E, et al. Failure of parturition in mice lacking the prostaglandin F receptor. Science. 1997;277:681-683.
90. Richards JS, Fitzpatrick S, Clemens JW, Morris JK, Alliston T, Sirois J. Ovarian cell differentiations cascade of multiple hormones, cellular signals, and regulated genes. Recent Prog Horm Res. 1995;50:223-254.
91. Tsafriri A. Ovulation as a tissue remodelling process. Proteolysis and cumulus expansion. Adv Exp Med Biol. 1995;377:121-140.
92. Li J, Simmons D, Tsang BK. Regulation of hen granulosa cell prostaglandin production by transforming growth factors during follicular development: involvement of cyclooxygenase II. Endocrinology. 1996;137:2522-2529.
93. Akil M, Amos RS, Stewart P. Infertility may sometimes be associated with NSAID consumption. Br J Rheumatol. 1996;35:76-78.
94. Thylan S. NSAIDs and fertility. Br J Rheumatol. 1996;36:145-146.
95. Athanasiou S, Bourne TG, Kalid A, et al. Effects of indomethacin on follicular structure, vascularity, and function over the periovulatory period in women. Fertil Steril. 1996;65:556-560.
96. Roberts R, Smith GW, Hall C, Nuke G. Leteinised unreputed follicles in women with inflammatory arthritis taking NSAIDs [abstract]. Br J Rheumatol. 1995;34(suppl 2):22.
97. Lim H, Dey S. Prostaglandin E-2 receptor sub-type EP2 gene expression in the mouse uterus coincides with differentiation of the luminal epithelium for implantation. Endocrinology. 1997; 138:4599-4606.
98. Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A. 1996;93:10417-10422.
99. McAdam BF, Catella-Lawson F, Mardini LA, Kapoor S, Lawson JA, Fitzgerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A. 1999;96:272-277.
100. Oshima M, Dinchuk J, Kargman SL, et al. Suppression of intestinal polyposis in APC δ716 knockout mice by inhibition of prostaglandin endoperoxide synthase-2 (COX-2). Cell. 1996;87: 803-809.
101. Minmouse model by the nonsteroidal anti-inflammatory drug piroxicam. Cancer Res. 1996;56:710-714.
102. Thun MJ, Namboodiri MM, Heath CWJ. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991;325:1593-1596.
103. Giardiello FM, Hamilton SR, Krush AJ, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993;328:1313-1316.
104. Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr. Aspirin use and risk of fatal cancer. Cancer Res. 1993;53:1322-1327.
105. Thun MJ. NSAID use and decreased risk of gastrointestinal cancers. Gastroenterol Clin North Am. 1996;25:333-348.
106. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994;121: 241-246.
107. Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med. 1995;333:609-614.
108. Williams CS, Smalley W, DuBois RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest. 1997;100:1325-1329.
109. Smalley WE, DuBois RN. Colorectal cancer and nonsteroidal antiinflammatory drugs. Adv Pharmacol. 1997;39:1-20.
110. Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 1995;55:2556-2559.
111. Hanif R, Pittras A, Feng Y, et al. Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem Pharm. 1996;52:237-245.
112. Sheng H, Shao J. Kirkland SC, et al. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest. 1997;99:2254-2259.
113. 2 in human colon cancer cells. Cancer Res. 1998;58:362-366.
114. Breitner JC, Welsh KA, Helms MJ, et al. Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995;16:523-530.
115. Breitner JC. Inflammatory processes and antiinflammatory drugs in Alzheimer's disease: a current appraisal. Neurobiol Aging. 1996;17:789-794.
116. Breitner JCS, Welsh KA, Helms MJ, et al. Delayed onset on Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995;16:523-530.
117. Steward WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997;48:626-632.
118. Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MMB, Hofman A. Do nonsteroidal anti-inflammatory drugs decrease the risk of Alzheimer's disease? The Rotterdam Study. Neurology. 1995;45:1441-1445.
119. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996;47: 425-432.
120. de la Torre JC. Cerebromicrovascular pathology in Alzheimer's disease compared to normal aging. Gerontology. 1997;43:26-43.