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Modulation of prostaglandin activity, part 1: Prostaglandin inhibition in the management of nonrheumatologic diseases: Immunologic and hematologic aspects

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Abstract

Prostaglandins (PGs) are active biologic substances that are involved in a wide range of physiologic processes; when their production is out of balance, they are factors in the pathogenesis of illness. Modulation of PGs by inhibition or stimulation is promising for the management of various conditions. PG inhibitors are widely used to relieve pain and inflammation in patients with rheumatologic disease. Interest in the use of PG inhibitors to prevent cancer and cardiovascular events is growing. More than 27 y ago, investigators found that PG depresses antibody production in vivo; reduces serum iron, hemoglobin, and leukoid series in bone marrow during acute and chronic blood loss; reduces albumin during antigenic stimulation; suppresses hypercalcemia after bleeding; and reduces fasting blood sugar and hyperglycemia after ether anesthesia and bleeding. Chronic conditions that produce large quantities of PGs are associated with immunosuppression and secondary anemia. Investigators in the present study hypothesized (1) that the overproduction of PGs is responsible for immunosuppression and secondary anemia in conditions associated with increased PG synthesis, such as pathologic inflammation, malignancy, trauma, and injury, and (2) that PG inhibitors reverse immunosuppression and secondary anemia, thereby enhancing the immune response. This is supported by many reports that show the immunosuppressive effects of PGs and their role in the immunosuppression associated with pathologic inflammation, burns, trauma, and tumors. Inhibition of PGs can be achieved through the use of synthetic medicines and natural products. This article reviews the effects of PGs and inhibition of increased synthesis of PGs on the lymphoid system, hematologic indices, and bone marrow elements in trauma, injury, burns, and tumors. The Medline database (1966–2006) was used in this study. Investigators in the present study and others have provided evidence that shows the involvement of PGs in immunosuppression and secondary anemia, as well as the efficacy of inhibited overproduction of PGs in many pathologic conditions other than rheumatologic disease.

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References

  1. Kam C, See AU. Cyclo-oxygenase isoenzymes: physiological and pharmacological role.Anaesthesia. 2000;55:442–449

    Article  PubMed  CAS  Google Scholar 

  2. Samuelsson B, Dahlen S, Lindgren JA, Rouzer CA, Serhan CN. Leukotrienes and lipoxins: structure, biosynthesis, and biological effects.Science. 1987;237:1171–1176

    Article  PubMed  CAS  Google Scholar 

  3. Stenson WF. Prostaglandins and epithelial response to injury.Curr Opin Gastroenterol. 2007;23:107–110

    Article  PubMed  CAS  Google Scholar 

  4. Rajakariar R, Yaqoob MM, Gilroy DW. COX-2 in inflammation and resolution.Mol Interv. 2006;6:199–207

    Article  PubMed  CAS  Google Scholar 

  5. Kim R, Emi M, Tanabe K. Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity.Immunology. 2006;119:254–264

    Article  PubMed  CAS  Google Scholar 

  6. Sohn HY, Krotz F. Cyclooxygenase inhibition and atherothrombosis.Curr Drug Targets. 2006;7:1275–1284

    Article  PubMed  CAS  Google Scholar 

  7. Al-Waili N, Al-Azzawi H, Al-Obidi S. Hypoglycaemic effect of prostaglandin F2 alpha in normal rabbits.J F Med Bagh. 1981;25:247–249

    Google Scholar 

  8. Al-Waili N, Al-Azzawi H. The effects of prostaglandin E2 on hyperglycemia following hemorrhage and ether anesthesia.J F Med Bagh. 1981;23:405–407

    CAS  Google Scholar 

  9. Al-Azzawi H, Al-Dabbagh A, Al-Waili N. The effects of PGF2 on hyperglycemic response to ether anesthesia and bleeding, Fourth Scientific Congress. Baghdad, Iraq: College of Medicine, University of Baghdad; 1988:34.

    Google Scholar 

  10. Al-Azzawi H, Al-Waili N. Serum calcium, serum inorganic phosphorus and serum alkaline phosphates during hemorrhage and prostaglandin E2 treatment.J F Med Bagh. 1981;23:349–352

    Google Scholar 

  11. Al-Waili N, Al-Azzawi H. The effects of prostaglandin E2 on serum iron following acute and chronic blood loss.Clin Exp Pharm Physiol. 1985;12:443–446

    Article  CAS  Google Scholar 

  12. Al-Waili N, Al-Azzawi H, Al-Niami M. Bone marrow cellular elements and peripheral blood indices following acute hemorrhage and prostaglandin E2 treatment.Saudi Med J. 1983;4:236–242

    Google Scholar 

  13. Al-Azzawi H, Al-Waili N. Haemopoietic changes following chronic blood loss and PGE2 treatment, First Scientific Congress. Baghdad, Iraq: College of Medicine, University of Baghdad; 1984:109

    Google Scholar 

  14. Al-Azzawi H, Al-Waili N, Thewani A. The effects of PGAl on serum protein components during primary and secondary immune responses.J F Med Bagh. 1981;23:54–60

    Google Scholar 

  15. Al-Waili N. Three cases of nephrotic syndrome treated by indomethacin.J Pak Med Assoc. 1988;28:54–56

    Google Scholar 

  16. Al-Waili N. Oxidant stress: A common cause for diseases.ALSaha Wltab [in Arabic]. 2002;188:19–25

    Google Scholar 

  17. Smith C, Zhang Y, Koboldt C, Muhammad J, Zweifel B. Pharmacological analysis of cyclooxygenase-1 in inflammation.Pharmacology. 1998;95:13313–13318

    CAS  Google Scholar 

  18. Portanova P, Zhang Y, Andersson D, Hanser D. Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia and interleukin 6 production in vivo.J Exp Med. 1996;186:883–891

    Article  Google Scholar 

  19. Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients.Toxicology. 2003;189:113–127

    Article  PubMed  CAS  Google Scholar 

  20. Chen L, Salafranca M, Mehat N. Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets.Am J Physiol. 1997;273:H1854-H1859

    PubMed  CAS  Google Scholar 

  21. DeGaetano C, Cerletti G, Dejana E, Latin R. Pharmacology of platelet inhibition in humans: implications of the salicylate-aspirin interaction.Circulation. 1985;72:1185–1193

    CAS  Google Scholar 

  22. Mehta J, Lawson L, Nichols W. Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and T×A2 inhibitor U-63557A.Am J Physiol. 1989;257:H1240-H1246

    PubMed  CAS  Google Scholar 

  23. Schreiber J, Mason R, Eling T. Detection of glutathione free radical catalyzed by prostaglandin hydroperoxidase present in intact epidermal cells.Fed Proc Fed Am Soc Exp Biol. 1986;45:70–75

    Google Scholar 

  24. Montuschi P, Barnes PJ, Roberts LJ. Isoprostanes: markers and mediators of oxidative stress.FASEB J. 2004;18:1791–1800

    Article  PubMed  CAS  Google Scholar 

  25. Mendelsohn J, Nordberg J. Adenylate cyclase in thymus-derived and bone marrow-derived lymphocytes from normal donors and patients with chronic lymphocytic leukemia.J Clin Invest. 1979;63:1124–1132

    Article  PubMed  CAS  Google Scholar 

  26. Dunn CD. Prostaglandins and erythropoiesis: structure/action relationships and identification of the prostaglandin responsive cells.Blut. 1981;42:307–314

    Article  PubMed  CAS  Google Scholar 

  27. Taniguchi S, Shibuya T, Harada M, Niho Y. Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells.Kidney Int. 1989;36:712–718

    Article  PubMed  CAS  Google Scholar 

  28. Fried W, Morley C, Barone-Varelas J, Bidani A, Prancan A. Effect of indomethacin and of prostaglandins on extrarenal erythropoietin production in rats.J Lab Clin Med. 1988;111:184–188

    PubMed  CAS  Google Scholar 

  29. Gentile P, Byer D, Pelus L. In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2.Blood. 1983;62:1100–1107

    PubMed  CAS  Google Scholar 

  30. Gentile P, Pelus L. In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of granulocyte-monocyte progenitor cell (CFU-GM) cell-cycle rate.Exp Hematol. 1987;15:119–126

    PubMed  CAS  Google Scholar 

  31. Karim S, Raq B. Prostaglandins and tumors. In: Karim SMM, ed.Prostaglandins: Physiological, Pharmacological and Pathological Aspects. Lancaster: MTP Press; 1976:145–178

    Google Scholar 

  32. Bennett A, Berstock DA, Raja B. Survival time after surgery is inversely related to the amount of prostaglandin extracted from human breast.Br J Pharmacol. 1979;66:451–456

    Google Scholar 

  33. Bennett A, Charlier E, MacDonald A. Bone destruction by breast cancer.Prostaglandins. 1979;11:461–469

    Article  Google Scholar 

  34. Grinwich K, Plescia O. Tumor-mediated immunosuppression: prevention by inhibitors of prostaglandin synthesis.Prostaglandins. 1977;14:1175–1178

    Article  PubMed  CAS  Google Scholar 

  35. Saito H, Tomioka H. Suppressive factor against macrophage phagocytosis produced by cultured sarcoma-180 cells.Gann. 1979;70:671–675

    PubMed  CAS  Google Scholar 

  36. Ting CC, Rodrigues D, Ting RC, Wivel N, Collins MJ. Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.Int J Cancer. 1979;24:644–655

    Article  PubMed  CAS  Google Scholar 

  37. Pelus L, Straussen H. Prostaglandins and the immune response.Life Sci. 1977;20:903–905

    Article  PubMed  CAS  Google Scholar 

  38. Goodwin S, Webb D. Regulation of the immune response by prostaglandins.Clin Immunol Immunopathol. 1980;15:106–110

    Article  PubMed  CAS  Google Scholar 

  39. Baker PE, Fahey JV, Munck A. Prostaglandin inhibition of T-cell proliferation is mediated at two levels.Cell Immunol. 1981;61:52–61

    Article  PubMed  CAS  Google Scholar 

  40. Kato K, Askenase P. Reconstitution of an inactive antigen-specific T cell suppressor factor by incubation of the factor with prostaglandins.J Immunol. 1984;133:2025–2031

    PubMed  CAS  Google Scholar 

  41. Goodwin S, Messner R, Peake G. Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro.J Clin Invest. 1978;62:753–756

    Article  PubMed  CAS  Google Scholar 

  42. Gordon D, Bray M, Morley J. Control of lymphokine secretion by prostaglandins.Nature. 1976;262:400–403

    Article  Google Scholar 

  43. Rappaport S, Dodge R. Prostaglandin E inhibits the production of human interleukin 2.J Exp Med. 1982;155:943–948

    Article  PubMed  CAS  Google Scholar 

  44. Parhar R, Yagel S, Lala P. PGE2-mediated immunosuppression by first trimester human decidual cells blocks activation of maternal leukocytes in the decidua with potential anti-trophoblast activity.Cell Immunol. 1989;120:61–74

    Article  PubMed  CAS  Google Scholar 

  45. Mannie MD, Prevost KD, Marinakis CA. Prostaglandin E2 promotes the induction of anergy during T helper cell recognition of myelin basic protein.Cell Immunol. 1995;160:132–138

    Article  PubMed  CAS  Google Scholar 

  46. Thompson P, Jelinek D, Lipsky P. Regulation of human B cell proliferation by prostaglandin E2.J Immunol. 1984;133:2446–2453

    PubMed  CAS  Google Scholar 

  47. Michelin M, Figueiredo F, Cunha F. Involvement of prostaglandins in the immunosuppression occurring during experimental infection by Paracoccidioides brasiliensis.Exp Parasitol. 2002;102:170–177

    PubMed  CAS  Google Scholar 

  48. Webb D, Wieder K, Rogers T, Healy C, Nowowiejski-Wieder I. Chemical identification of a prostaglandin-induced T suppressor (PITS).Lymphokine Res. 1985;4:139–149

    PubMed  CAS  Google Scholar 

  49. Brunda M, Herberman R, Holden H. Inhibition of murine natural killer cell activity by prostaglandins.J Immunol. 1980;124:2682–2687

    PubMed  CAS  Google Scholar 

  50. Iberer F, Wasler A, Tscheliessnigg K, et al. Prostaglandin E1 reduces the frequency of rejection after heart transplantation.J Heart Lung Transplant. 1992;11(4 Pt 1):727–732

    PubMed  CAS  Google Scholar 

  51. Alvarellos A, Lipsky P, Jasin H. Prostaglandin E2 modulation of rheumatoid factor synthesis.Arthritis Rheum. 1988;31:1473–1480

    Article  PubMed  CAS  Google Scholar 

  52. Gualde N, Harizi H. Prostanoids and their receptors that modulate dendritic cell-mediated immunity.Immunol Cell Biol. 2004;82:353–360

    Article  PubMed  CAS  Google Scholar 

  53. Hart P, Townley S, Grimbaldeston M, Khalil Z, Finlay-Jones J. Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression.Methods. 2002;28:79–89

    Article  PubMed  CAS  Google Scholar 

  54. Josten C, Griga T, Muhr G. Immunostimulation with ibuprofen in chronic osteitis: an experimental study.Unfallchirurg. 1991;94:191–193

    PubMed  CAS  Google Scholar 

  55. Kozlov V, Poveshchenko A, Gromykhina N. Some mechanisms involved in the prostaglandin E2 immunosuppressive effect in (CBA × C57BL) F1 mice in vivo.Cell Immunol. 1990;128:242–249

    Article  PubMed  CAS  Google Scholar 

  56. Milch P, Salvatore W, Luft B, Baker D. Suppression of newborn natural killer cell activity by prostaglandin E2.Am J Obstet Gynecol. 1988;159:47–51

    Google Scholar 

  57. Moran M, Mozes M, Maddux M, et al. Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone.N Engl J Med. 1990;322:1183–1188

    Article  PubMed  CAS  Google Scholar 

  58. Iyengar S, Contreras P, Mick S, Bremer M, McKearn J. Immune modifying effects of misoprostol and natural prostaglandins.Br J Rheumatol. 1991;30(suppl 2):71–74

    Google Scholar 

  59. Menger M, Vollmar B. Surgical trauma: hyperinflammation versus immunosuppression?Langenbecks Arch Surg. 2004;389:475–484

    Article  PubMed  Google Scholar 

  60. Mackrell P, Daly J, Mestre J, et al. Elevated expression of cyclooxygenase-2 contributes to immune dysfunction in a murine model of trauma.Surgery. 2001;130:826–833

    Article  PubMed  CAS  Google Scholar 

  61. Schaffer M, Barbul A. Lymphocyte function in wound healing and following injury.Br J Surg. 1998;85:444–460

    Article  PubMed  CAS  Google Scholar 

  62. Ogawa K, Hirai M, Katsube T. Suppression of cellular immunity by surgical stress.Surgery. 2000;127:329–336

    Article  PubMed  CAS  Google Scholar 

  63. Ben-Eliyahu S. The promotion of tumor metastasis by surgery and stress: immunological basis and implications for psychoneuroimmunology.Brain Behav Immun. 2003;17:S27-S36

    Article  PubMed  CAS  Google Scholar 

  64. Ertel W, Morrison MH, Ayala A, Chaudry IH. Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis.Arch Surg. 1992;127:70–75

    PubMed  CAS  Google Scholar 

  65. Ross W, Leaver H, Yap P, et al. Macrophage prostaglandin E2 and oxidative responses to endotox-in during immunosuppression associated with anaesthesia and transfusion.Prostaglandins Leukot Essent Fatty Acids. 1993;49:945–953

    Article  PubMed  CAS  Google Scholar 

  66. Shelby J, Hisatake G. Effect of ibuprofen and interleukin 2 on transfusion-induced suppression of cell-mediated immunity.Arch Surg. 1988;123:1397–1399

    PubMed  CAS  Google Scholar 

  67. Asselin P, Benquet C, Krzystyniak K, Brousseau P, Savard R, Fournier M. In vivo indomethacin reverses exercise-induced immunosuppression in rats.Int J Immunopharmacol. 1996;18:491–497

    Article  PubMed  CAS  Google Scholar 

  68. Shimazu S. Evaluation of immunosuppressive properties of fluid from healing wounds and influence of prostaglandins.Nippon Geka Gakkai Zasshi. 1987;88:1667–1675

    PubMed  CAS  Google Scholar 

  69. Ozaki-Okayama Y, Matsumura K, Ibuki T, et al. Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats.Crit Care Med. 2004;32:795–800

    Article  PubMed  Google Scholar 

  70. Schwacha MG, Chung CS, Ayala A, Bland KI, Chaudry IH. Cyclooxygenase 2-mediated suppression of macrophage interleukin-12 production after thermal injury.Am J Physiol Cell Physiol. 2002;282:C263-C270

    PubMed  CAS  Google Scholar 

  71. Enkhbaatar P, Murakami K, Shimoda K, et al. Ketorolac attenuates cardiopulmonary derange-ments in sheep with combined burn and smoke inhalation injury.Clin Sci. 2003;105:621–628

    Article  PubMed  CAS  Google Scholar 

  72. Santangelo S, Shoup M, Gamelli RL, Shankar R. Prostaglandin E2 receptor antagonist (SC-19220) treatment restores the balance to bone marrow myelopoiesis after burn sepsis.J Trauma. 2000;48:826–830

    PubMed  CAS  Google Scholar 

  73. Shoup M, Weisenberger JM, Wang JL, Pyle JM, Gamelli RL, Shankar R. Mechanisms of neu-tropenia involving myeloid maturation arrest in burn sepsis.Ann Surg. 1998;228:112–122

    Article  PubMed  CAS  Google Scholar 

  74. Gamelli RL, He LK, Liu H, Ricken JD. Burn wound infection-induced myeloid suppression: the role of prostaglandin E2, elevated adenylate cyclase, and cyclic adenosine monophosphate.J Trauma. 1998;44:469–474

    PubMed  CAS  Google Scholar 

  75. Gamelli R, He L, Liu L. Macrophage mediated suppression of granulocyte and macrophage growth after burn wound infection reversal by means of anti-PGE2.J Burn Care Rehabil. 2000;21:64–69

    PubMed  CAS  Google Scholar 

  76. Yamamoto H, Siltharm S, deSerres S, Hultman C, Meyer A. Effect of cyclo-oxygenase inhibition on in vitro B-cell function after burn injury.J Trauma. 1996;41:612–619

    PubMed  CAS  Google Scholar 

  77. Latter D, Tchervenkov I, Nohr C, Christou N. The effect of indomethacin on burn-induced immunosuppression.J Surg Res. 1987;43:246–252

    Article  PubMed  CAS  Google Scholar 

  78. Colacchio TA, Yeager P, Hildebrandt LW. Perioperative immunomodulation in cancer surgery.Am J Surg. 1994;167:174–179

    Article  PubMed  CAS  Google Scholar 

  79. Knoferl MW, Diodato MD, Schwacha MG, Cioffi WG, Bland KI, Chaudry IH. Cyclooxygenase-2-mediated regulation of Kupffer cell interleukin-6 production following trauma—hemorrhage and subsequent sepsis.Shock. 2001;16:479–483

    PubMed  CAS  Google Scholar 

  80. Gogos CA, Maroulis J, Zoumbos NC, Salsa B, Kalfarentzos F. The effect of parenteral indomethacin on T-lymphocyte subpopulations and cytokine production in patients under major surgical operations.Res Exp Med (Berl). 1995;195:85–92

    Article  CAS  Google Scholar 

  81. Hansbrough J, Zapata-Sirvent R, Shackford S, Hoyt D, Carter W. Immunomodulating drugs increase resistance against sepsis in traumatized mice.J Trauma. 1986;26:625–630

    PubMed  CAS  Google Scholar 

  82. Al-Waili N, Butler G, Beale J, Hamilton R, Lee B, Lucas P. Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy.Med Sci Monit. 2005;11:279–289

    Google Scholar 

  83. Al-Waili N. Medicine of balance and diseases triad: new concept and nomenclatures.FASEB J. 2003;17:453

    Google Scholar 

  84. Al-Waili N, Thewani A, Al-Azzawi H. The effects of PGA1 on antibody production: World Conference on Clinical Pharmacology and Therapeutics.London: XX; 1980:246

    Google Scholar 

  85. Al-Waili N, Thewani A, Al-Azzawi H. Prostaglandin A1 and antibody production.J F Med Bagh. 1981;23:32–35

    Google Scholar 

  86. Al-Waili N, Al-Azzawi H, Al-Rawi Z. Treatment of advanced chorionic carcinoma by indomethacin and steroids.Saudi Med J. 1984;5:81–86

    Google Scholar 

  87. Al-Waili N. Indomethacin in basal cell carcinoma.J Pak Med Assoc. 1989;39:134–136

    PubMed  CAS  Google Scholar 

  88. Takit M, Inada M, Maruyama T, Miyaura C. Prostaglandin E receptor EP4 antagonist suppresses osteolysis due to bone metastasis of mouse malignant melanoma cells.FEBS Lett. 2007 Feb 6; 581(3):565–71

    Article  CAS  Google Scholar 

  89. Eisinger AL, Prescott SM, Jones DA, Stafforini DM. The role of cyclooxygenase-2 and prostaglandins in colon cancer.Prostaglandins Other Lipid Mediat. 2007;82:147–154

    Article  PubMed  CAS  Google Scholar 

  90. Newman SJ, Mrkonjich L. Cyclooxygenase-2 expression in feline pancreatic adenocarcinomas.J Vet Diagn Invest. 2006 Nov;18(6):590–3

    PubMed  Google Scholar 

  91. Piazuelo E, Jimenez P, Strunk M, Santander S, Garcia A, Esteva F, Lanas A. Effects of selective PGE2 receptor antagonists in esophageal adenocarcinoma cells derived from Barrett’s esophagus.Prostaglandins Other Lipid Mediat. 2006 Dec;81(3–4):150–61

    Google Scholar 

  92. Sandler A, Dubinett S. COX-2 inhibition and lung cancer.Semin Oncol. 2004;31(2 suppl 7):45–52

    Article  CAS  Google Scholar 

  93. Krishnan K, Brenner D. Prostaglandin inhibitors and the chemoprevention of noncolonic malignancy.Gastroenterol Clin North Am. 2001;30:981–1000

    Article  PubMed  CAS  Google Scholar 

  94. Earnest DL, Hixson LJ, Alberts DS. Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention.J Cell Biochem Suppl. 1992;161:156–166

    Article  Google Scholar 

  95. Arun B, Goss P. The role of COX-2 inhibition in breast cancer treatment and prevention.Semin Oncol. 2004;31(2 suppl 7):22–29.

    Article  PubMed  CAS  Google Scholar 

  96. Ishihara S, Rumi MA, Okuyama T, Kinoshita Y. Effect of prostaglandins on the regulation of tumor growth.Curr Med Chem Anticancer Agents. 2004;4:379–387.

    Article  PubMed  CAS  Google Scholar 

  97. Toshihiko K, Naoaki U, Seiichi N, et al. Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on breast cancer development.Carcinogenesis. 2001;22:2001–2004.

    Article  Google Scholar 

  98. Ding X, Tong W, Adrian T. Cyclooxygenases and lipoxygenase as potential targets for treatment of pancreatic cancer.Pancreatology. 2001;1:291–299.

    Article  PubMed  CAS  Google Scholar 

  99. Lieb J. Antidepressants, eicosanoids and the prevention and treatment of cancer: a review.Prostaglandins Leukot Essent Fatty Acids. 2001;65:233–239.

    Article  PubMed  CAS  Google Scholar 

  100. Choy H, Milas L. Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance?J Natl Cancer Inst. 2003;95:1440–1452.

    PubMed  CAS  Google Scholar 

  101. Rodrigues S, Bruyneel E, Rodrigues CM, Shahin E, Gespach C. Cyclooxygenase 2 and carcinogenesis.Bull Cancer. 2004;91(suppl 2):S61-S76.

    Google Scholar 

  102. Pockaj B, Basu G, Pathangey L, et al. Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer.Ann Surg Oncol. 2004;11:328–339.

    Article  PubMed  Google Scholar 

  103. Pawelec G, Zeuthen J, Kiessling R. Escape from host-antitumor immunity.Crit Rev Oncog. 1997;8:111–141.

    PubMed  CAS  Google Scholar 

  104. Hellstrom K, Hellstrom I. Novel approaches to therapeutic cancer vaccines.Expert Rev Vaccines. 2003;2:517–532.

    Article  PubMed  CAS  Google Scholar 

  105. Foss F. Immunologic mechanisms of antitumor activity.Semin Oncol. 2002;29(3 suppl 7):5–11.

    Article  CAS  Google Scholar 

  106. Kim S, Iizuka K, Aguila H. In vivo natural killer cell activities revealed by natural killer cell-deficient mice.Proc Natl Acad Sci USA. 2000;97:2731–2736.

    Article  PubMed  CAS  Google Scholar 

  107. Lanier L. On guard-activating NK cell receptors.Nat Immunol. 2001;2:23–27.

    Article  PubMed  CAS  Google Scholar 

  108. Botti C, Seregni E, Ferrari L, Martinetti A, Bombardieri E. Immunosuppressive factors: role in cancer development and progression.Int J Biol Markers. 1998;13:51–69.

    PubMed  CAS  Google Scholar 

  109. Paul S, Calmels B, Regulier E. Tumor-induced immunosuppression.Ann Biol Clin (Paris). 2002;60:143–512.

    CAS  Google Scholar 

  110. Garcia-Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape.J Cell Physiol. 2003;195:346–355.

    Article  PubMed  CAS  Google Scholar 

  111. Ohm JE, Carbone DP. Immune dysfunction in cancer patients.Oncology (Williston Park). 2002;16(1 suppl 1):11–18.

    Google Scholar 

  112. al-Sarireh B, Eremin O. Tumor-associated macrophages (TAMS): disordered function, immune suppression and progressive tumor growth.J R Coll Surg Edinb. 2000;45:1–16.

    PubMed  CAS  Google Scholar 

  113. Bronte V, Serafini P, Apolloni E, Zanovello P. Tumor-induced immune dysfunctions caused by myeloid suppressor cells.J Immunother. 2001;24:431–446.

    Article  PubMed  CAS  Google Scholar 

  114. Alleva D, Burger C, Elgert K. Tumor growth causes suppression of autoreactive T-cell proliferation by disrupting macrophage responsiveness to interferon-gamma.Scand J Immunol. 1994;39:31–38.

    Article  PubMed  CAS  Google Scholar 

  115. Loh JK, Hwang SL, Lieu AS, Huang TY, Howng SL. The alteration of prostaglandin E2 levels in patients with brain tumors before and after tumor removal.J Neurooncol. 2002;57:147–150.

    Article  PubMed  Google Scholar 

  116. Dix A, Brooks W, Roszman T, Morford L. Immune defects observed in patients with primary malignant brain tumors.J Neuroimmunol. 1999;100:216–232.

    Article  PubMed  CAS  Google Scholar 

  117. Yurochko A, Burger C, Elgert K. Tumor modulation of autoreactivity: decreased macrophage and autoreactive T cell interactions.Cell Immunol. 1990;127:105–119.

    Article  PubMed  CAS  Google Scholar 

  118. Stanojevic-Bakic N, Vuckovic-Dekic L, Susnjar S, Spuzic I. In vitro effect of indomethacin on mitogen-induced lymphoproliferative response in lung cancer patients.Neoplasma. 1992;39:129–132.

    PubMed  CAS  Google Scholar 

  119. Nakajima I, Chu T. Prostaglandin E2-mediated suppression of murine lymphokine-activated killer cell activity generated from tumor-bearing hosts by interferon-gamma.Mol Biother. 1990;2:228–232.

    PubMed  CAS  Google Scholar 

  120. Sombroek C, Stam A, Masterson A, et al. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation.J Immunol. 2002;168:4333–4343.

    PubMed  CAS  Google Scholar 

  121. Kalmar L, Gyires K, Gergely P. Inhibitory effect of tumor cells on leukocyte motility.Immunol Lett. 1984;8:175–177.

    Article  PubMed  CAS  Google Scholar 

  122. Tisdale M. Role of prostaglandins in metastatic dissemination of cancer: minireview on cancer research.Exp Cell Biol. 1983;51:250–256.

    CAS  Google Scholar 

  123. DeGowin R, Gibson DP, Knapp SA. Prostaglandin E and the erythropoietic and stromal insufficiency induced by extramedullary tumor.J Lab Clin Med. 1981;98:217–226.

    PubMed  CAS  Google Scholar 

  124. Plescia OJ, Pontieri GM, Brown J, et al. Amplification by macrophages of prostaglandin-mediated immunosuppression in mice bearing syngeneic tumors.Prostaglandins Leukot Med. 1984;16:205–223.

    Article  PubMed  CAS  Google Scholar 

  125. DeGowin R, Gibson D, Knapp S, Wathen L. Tumor-induced suppression of marrow stromal colonies.Exp Hematol. 1981;9:811–819.

    PubMed  CAS  Google Scholar 

  126. Monnerat C, Leyvraz S. Tumor anemia: overview of the role of human recombinant erythropoietin (r-hu-EPO) in treatment of tumor anemia.Schweiz Rundsch Med Prax. 1999;88:178–188.

    PubMed  CAS  Google Scholar 

  127. Manegold C. The causes and prognostic significance of low hemoglobin levels in tumor patients.Strahlenther Onkol. 1998;174(suppl 4):17–19.

    Google Scholar 

  128. Birgegard G, Aapro MS, Bokemeyer C, et al. Cancer-related anemia: pathogenesis, prevalence and treatment.Oncology. 2005;68(suppl 1):3–11.

    Article  PubMed  Google Scholar 

  129. Bron D, Meuleman N, Mascaux C. Biological basis of anemia.Semin Oncol. 2001;28(2 suppl 8):1–6.

    Article  PubMed  CAS  Google Scholar 

  130. Al-Waili N. Treatment of primary nocturnal enuresis by diclofenac sodium: double blind crossover study.Clin Exp Pharma Physiol. 1988;12:139–142.

    Google Scholar 

  131. Al-Waili N. Indomethacin suppositories: an alternative treatment for nocturnal frequency of micturition.IRCS Med Sci. 1986;14:322–323.

    Google Scholar 

  132. Al-Waili N. Indomethacin suppositories in the treatment of primary nocturnal enuresis: double-blind study.J Urol. 1988;142:1290–1292.

    Google Scholar 

  133. Al-Waili N. Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.BJU Int. 2002;90:295–301.

    Article  Google Scholar 

  134. Al-Waili N, Al-Waili T, Al-Waili A, Saloom K. Urinary nitrite excretion and urinary variables in patients with primary nocturnal frequency of micturition: effects of indomethacin.World J Urol. 2005;24:1–8.

    Google Scholar 

  135. Al-Waili N. Carbamazepine to treat primary nocturnal enuresis: double-blind study.Eur J Med Res. 2000;5:40–44.

    PubMed  CAS  Google Scholar 

  136. Al-Waili NS, Al-Waili H, Saloom KY, et al. Effect of carbamazepine on urinary volume and osmolality, water clearance, and serum osmolality in patients with primary enuresis.Eur Urol. 2006;50:844–849.

    Article  PubMed  CAS  Google Scholar 

  137. Al-Waili N. Prostaglandin synthesis inhibition with indomethacin rectal suppositories in the treatment of acute and chronic urinary calculus obstruction.Clin Exp Pharm Physiol. 1986;13:195–199.

    Article  CAS  Google Scholar 

  138. Al-Waili N. Clinical usefulness of nifedipine in the treatment of acute and chronic urinary colic.Med Sci Res. 1989;16:567–568.

    Google Scholar 

  139. Al-Waili NS. Intramuscular tenoxicam to treat acute renal colic.Br J Urol. 1996;77:15–16.

    PubMed  CAS  Google Scholar 

  140. Al-Waili N., Saloom K. Intramuscular piroxicam to treat acute renal colic: comparison with intramuscular diclofenac sodium.Eur J Med Res. 1999;4:23–27.

    PubMed  CAS  Google Scholar 

  141. Al-Waili N., Saloom K. Intravenous tenoxicam to treat acute renal colic: comparison with antispasmodics.J Pak Med Assoc. 1998;48:370–372.

    PubMed  CAS  Google Scholar 

  142. Al-Waili N. Sublingual meloxicam for renal colic.Urol Int. 2001;67:119–120.

    Article  Google Scholar 

  143. Al-Waili N. Diclofenac sodium in intractable epilepsy.Acta Neurol Scand. 1987;73:507.

    Google Scholar 

  144. Al-Waili N. Two cases of psoriasis and high doses of indomethacin.Emir Med J. 1987;5:61–65.

    Google Scholar 

  145. Al-Waili N, Khalaf Z. Indomethacin suppositories in primary dymenorrhoea: double-blind crossover study.Ind J Med Res. 1990;92:298–301.

    CAS  Google Scholar 

  146. Al-Waili N. Intramuscular tenoxicam to treat primary dysmenorrhoea: double-blind study.Curr Opin Clin Exp Res. 2001;3:108–120.

    CAS  Google Scholar 

  147. Al-Waili N, Saloom K. The analgesic effects of intravenous tenoxicam in acute biliary colic: comparison with hyposcine N-butylbromide.Eur J Med Res. 1998;3:457–461.

    Google Scholar 

  148. Al-Waili N. Treatment of menstrual migraine with prostaglandin synthesis inhibitor mefenamic acid:double-blind study with placebo.Eur J Med Res. 2000;5:176–182.

    PubMed  CAS  Google Scholar 

  149. Al-Waili N. Efficacy and safety of repeated intramuscular injection of diclofenac sodium in the treatment of postcaesarean section pain: double-blind study.Arch Med Res. 2001;32:148–154.

    Article  PubMed  CAS  Google Scholar 

  150. Al-Waili N. Indomethacin suppositories for premature uterine contraction.FASEB J. 2001;15:235.

    Google Scholar 

  151. Saloom K, Al-Waili N. Intramuscular salicylate to treat acute migraine attacks: double-blind placebo controlled study.FASEB J. 2001;15:905.

    Google Scholar 

  152. Saloom K, Al-Waili N. Tenoxicam as an alternative to pethidine for postoperative pain.Pharmacol Toxicol. 2001;89(suppl 1):134.

    Google Scholar 

  153. Al-Waili N. Diclofenac to treat post-operative pain. Presented at: 30th Arab Medical Union Conference; July 15–17, 1997; Sanaa, Yemen.

  154. Sharma S. An update on eicosanoids and inhibitors of cyclooxygenase enzyme system.Ind J Expl Biol. 1997;35:1025–1031.

    CAS  Google Scholar 

  155. Altman D. Neutrophil activation: an alternative to prostaglandin inhibition as the mechanism of action for NSAIDs.Semin Arthritis Rheum. 1990;19(4 suppl 2):1–5.

    Google Scholar 

  156. Ikeda Y, Matsumato K, Dohi K, Jimbo H, Sasaki K, Satoh K. Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using spin trap method.Headache. 2001;41:138–144.

    Article  PubMed  CAS  Google Scholar 

  157. Masue T, Dohi S, Asano T, Shimonatka H. Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rat.Anesthesiology. 1999;91:198–206.

    Article  PubMed  CAS  Google Scholar 

  158. Kankaanranta H, Moilanen E, Vapaatalo H. Effects of non-steroidal anti-inflammatory drugs on polymorphonuclear leukocyte function in vitro: focus on fenamates.Naunyn Schmiedebergs Arch Pharmacol. 1994;350:685–691.

    Article  PubMed  CAS  Google Scholar 

  159. Gregorian S, Battisto J. Immunosuppression in murine renal cell carcinoma. II. Identification of responsible lymphoid cell phenotypes and examination of elimination of suppression.Cancer Immunol Immunother. 1990;31:335–341.

    Article  PubMed  CAS  Google Scholar 

  160. Manning LS, Bowman RV, Davis MR, Musk AW, Robinson BW. Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma.Clin Immunol Immunopathol. 1989;53:68–77.

    Article  PubMed  CAS  Google Scholar 

  161. Wasserman J, Blomgren H, Rotstein S, Petrini B, Hammarstrom S. Immunosuppression in irradiated breast cancer patients: in vitro effect of cyclooxygenase inhibitors.Bull N Y Acad Med 1989;65:36–44.

    PubMed  CAS  Google Scholar 

  162. Wang Z, Chen Y, Zheng R, et al. In vitro effects of prostaglandin E2 or indomethacin on the proliferation of lymphokine-activated killer cells and their cytotoxicity against bladder tumor cells in patients with bladder cancer.Prostaglandins. 1997;54:769–779.

    Article  PubMed  CAS  Google Scholar 

  163. Bennett A, Berstock D, Carrol M. Enhanced anticancer effects by combining cytotoxic drugs with the prostaglandin synthesis inhibitor flurbiprofen.Br J Pharmacol. 1981;74:208P-212P.

    Google Scholar 

  164. Brown J, DuBois R. COX-2: a molecular target for colorectal cancer prevention.J Clin Oncol. 2005;23:2840–2855.

    Article  PubMed  CAS  Google Scholar 

  165. Kinoshita T. Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells.Biochim Biophys Acta. 1999;1438:120–130.

    PubMed  CAS  Google Scholar 

  166. Kawamura T. Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation.J Neurochem. 1999;72:1907–1914.

    Article  PubMed  CAS  Google Scholar 

  167. Liu X, Yao S, Kirschenbaum A, Levine A. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells.Cancer Res. 1998;58:4245–4249.

    PubMed  CAS  Google Scholar 

  168. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2).Cell. 1996;87:803–809.

    Article  PubMed  CAS  Google Scholar 

  169. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.N Engl J Med. 2000;342:1946–1952.

    Article  PubMed  CAS  Google Scholar 

  170. Rahme E, Barkun AN, Toubouti Y, Bardou M. The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence.Gastroenterology. 2003;125:404–412.

    Article  PubMed  CAS  Google Scholar 

  171. Bardou M, Barkun AN, Ghosn J, Hudson M, Rahme E. Effect of chronic intake of NSAIDs and cyclooxygenase 2-selective inhibitors on esophageal cancer incidence.Clin Gastroenterol Hepatol. 2004;2:880–884.

    Article  PubMed  CAS  Google Scholar 

  172. Morgan G, Vainio H. Barrett’s esophagus, esophageal cancer and colon cancer: an explanation of the association and cancer chemopreventive potential of non-steroidal anti-inflammatory drugs.Eur J Cancer Prev. 1998;7:195–199.

    Article  PubMed  CAS  Google Scholar 

  173. Jiang X, Wong B. Cyclooxygenase-2 inhibition and gastric cancer.Curr Pharm Des. 2003;9:2281–2288.

    Article  PubMed  CAS  Google Scholar 

  174. Piazuelo E, Jimenez P, Lanas A. COX-2 inhibition in esophagitis, Barrett’s esophagus and esophageal cancer.Curr Pharm Des. 2003;9:2267–2280.

    Article  PubMed  CAS  Google Scholar 

  175. Ahnen D. Colon cancer prevention by NSAIDs: what is the mechanism of action.Eur J Surg Suppl. 1998;582:111–114.

    Article  PubMed  Google Scholar 

  176. Terry MB, Gammon MD, Zhang FF, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk.JAMA. 2004;291:2433–2440.

    Article  PubMed  CAS  Google Scholar 

  177. Rao C, Reddy B. NSAIDs and chemoprevention.Curr Cancer Drug Targets. 2004;4:29–42.

    Article  PubMed  CAS  Google Scholar 

  178. Boorman GA, Luster MI, Dean JH, Luebke RW. Effect of indomethacin on the bone marrow and immune system of the mouse.J Clin Lab Immunol. 1982;7:119–126.

    PubMed  CAS  Google Scholar 

  179. O’Reilly M, Gamelli RL. Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment.Exp Hematol. 1990;18:974–978.

    PubMed  CAS  Google Scholar 

  180. Pelus L. Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony-forming units-granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha.J Immunol. 1989;143:4171–4179.

    PubMed  CAS  Google Scholar 

  181. Akarca US. Gastrointestinal effects of selective and non-selective non-steroidal anti-inflammatory drugs.Curr Pharm Des. 2005;11:1779–1793.

    Article  PubMed  CAS  Google Scholar 

  182. Steen KS, Lems WF, Dijkmans BA. Effectiveness, safety, and costs of measures for prevention of gastropathy due to the use of nonsteroidal antiinflammatory drugs.Ned Tijdschr Geneeskd. 1999;143:1649–1652.

    PubMed  CAS  Google Scholar 

  183. Davies NM. Toxicity of nonsteroidal anti-inflammatory drugs in the large intestine.Dis Colon Rectum. 1995;38:1311–1321.

    Article  PubMed  CAS  Google Scholar 

  184. Sulowicz W, Stompor T, Tabor B. Nonsteroidal anti-inflammatory drugs—nephrotoxic mechanism of action.Przegl Lek. 1999;56:169–174.

    PubMed  CAS  Google Scholar 

  185. Frishman W. Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema.Am J Cardiol. 2002;89:18D-25D.

    Article  PubMed  CAS  Google Scholar 

  186. Ostensen ME, Skomsvoll JF. Anti-inflammatory pharmacotherapy during pregnancy.Expert Opin Pharmacother. 2004;5:571–580.

    Article  PubMed  CAS  Google Scholar 

  187. Bannwarth B, Berenbaum F. New nonsteroidal anti-inflammatory agents: nitric oxide donors and selective cyclooxygenase-2 inhibitors.Rev Med Interne. 1999;20(suppl 3):341s-345s.

    Article  Google Scholar 

  188. Wong S, Mitsumasa F, Melnyk P, Rodger I, Giaid A. Induction of cyclooxygenase-2 and activation of nuclear factor-kB in myocardium of patients with congestive heart failure.Circulation. 1988;98:100–103.

    Google Scholar 

  189. Yang X, Ma N, Szabolcs MJ, et al. Upregulation of COX-2 during cardiac allograft rejection.Circulation. 2000;101:430–438.

    PubMed  CAS  Google Scholar 

  190. Moncada S, Higgs J, Vane J. Human arterial and venous tissues generate prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation.Lancet. 1977;1:18–20.

    Article  PubMed  CAS  Google Scholar 

  191. McAdam BF, Catella-Lawson F, Mardini IA, 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 USA. 1999;96:272–277.

    Article  PubMed  CAS  Google Scholar 

  192. Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids.J Pharmacol Exp Ther. 1999;289:735–741.

    PubMed  CAS  Google Scholar 

  193. Hennan JK, Huang J, Barrett TD, et al. Effects of selective cyclooxygenase-2 inhibition on vascu-lar responses and thrombosis in canine coronary arteries.Circulation. 2001;104:820–825.

    Article  PubMed  CAS  Google Scholar 

  194. Pidgeon GP, Tamosiuniene R, Chen G, et al. Intravascular thrombosis after hypoxia-induced pulmonary hypertension: regulation by cyclooxygenase-2.Circulation. 2004;110:2701–2707.

    Article  PubMed  Google Scholar 

  195. Bombardier C, Laine L, Reicin A. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.N Engl J Med. 2000;343:1520–1528.

    Article  PubMed  CAS  Google Scholar 

  196. Mukherjee D, Nissen SE, Topol RJ. Risk of cardiovascular events associated with selective COX-2 inhibitors.JAMA. 2001;286:954–959.

    Article  PubMed  CAS  Google Scholar 

  197. Konstam MA, Weir MR, Reicin A. Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib.Circulation. 2001;104:2280–2288.

    Article  PubMed  CAS  Google Scholar 

  198. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.BMJ. 2006;332:1302–1308.

    Article  PubMed  CAS  Google Scholar 

  199. Wong M, Chowienczyk P, Kirkham B. Cardiovascular issues of COX-2 inhibitors and NSAIDs.Aust Fam Physician. 2005;34:945–948.

    PubMed  Google Scholar 

  200. Andersohn F, Suissa S, Garbe E. Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction.Circulation. 2006;113:1950–1957.

    Article  PubMed  CAS  Google Scholar 

  201. Reikvam A, Hexeberg S, Kvien TK, et al. Clinical use of COX inhibitors—a consensus.Tidsskr Nor Laegeforen. 2006;126:591–595.

    PubMed  Google Scholar 

  202. Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis.J R Soc Med. 2006;99:132–140.

    Article  PubMed  CAS  Google Scholar 

  203. Solomon SD, McMurray JJ, Pfeffer MA, Adenoma Prevention With Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.N Engl J Med. 2005;352:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  204. Ott E, Nussmeier NA, Duke PCl. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery.J Thorac Cardiovasc Surg. 2003;125:1481–1492.

    Article  PubMed  CAS  Google Scholar 

  205. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.N Engl J Med. 2005;352:1081–1091.

    Article  PubMed  CAS  Google Scholar 

  206. Jüni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis.Lancet. 2004;364:2021–2029.

    Article  PubMed  CAS  Google Scholar 

  207. Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2.Science. 2002;296:539–541.

    Article  PubMed  CAS  Google Scholar 

  208. Altman R, Luciardi HL, Muntaner J, et al. Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation: the Nonsteroidal Anti-inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study.Circulation. 2002;106:191–195.

    Article  PubMed  CAS  Google Scholar 

  209. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study:pp a randomized controlled trial.JAMA. 2000;284:1247–1255.

    Article  PubMed  CAS  Google Scholar 

  210. Solomon DH, Glynn RJ, Levin R. Nonsteroidal anti-inflammatory drug use and acute myocardial infarction.Arch Intern Med. 2002;162:1099–1104.

    Article  PubMed  CAS  Google Scholar 

  211. Rahme E, Pilote L, LeLorier J. Association between naproxen use and protection against acute myocardial infarction.Arch Intern Med. 2002;162:1111–1115.

    Article  PubMed  CAS  Google Scholar 

  212. Hawkey CJ, Hawkey GM, Everitt S, Skelly MM, Stack WA, Gray D. Increased risk of myocardial infarction as first manifestation of ischemic heart disease and nonselective nonsteroidal anti-inflammatory drugs.Br J Clin Pharmacol. 2006;61:730–737.

    Article  PubMed  CAS  Google Scholar 

  213. Fiorucci S, Antonelli E. NO-NSAIDs: from inflammatory mediators to clinical readouts.Inflamm Allergy Drug Targets. 2006;5:121–131.

    PubMed  CAS  Google Scholar 

  214. Muscara MN, Wallace JL. COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular and renal function.Cardiovasc Hematol Agents Med Chem. 2006;4:155–164.

    PubMed  CAS  Google Scholar 

  215. Turnbull CM, Cena C, Fruttero R, Gasco A, Rossi AG, Megson IL. Mechanism of action of novel NO-releasing furoxan derivatives of aspirin in human platelets.Br J Pharmacol. 2006;148:517–526.

    Article  PubMed  CAS  Google Scholar 

  216. Rigas B, Kalofonos H, Lebovics E, Vagenakis AG. NO-NSAIDs and cancer: promising novel agents.Dig Liver Dis. 2003;35(suppl 2):S27-S34.

    Article  CAS  Google Scholar 

  217. Ouyang N, Williams JL, Tsioulias GJ, et al. Nitric oxide-donating aspirin prevents pancreatic cancer in a hamster tumor model.Cancer Res. 2006;66:4503–4511.

    Article  PubMed  CAS  Google Scholar 

  218. Rigas B, Kashfi K. Nitric-oxide-donating NSAIDs as agents for cancer prevention.Trends Mol Med. 2004;10:324–330.

    Article  PubMed  CAS  Google Scholar 

  219. Al-Waili N. Oxidants and antioxidants in breast cancer: possible tumor marker.FASEB J. 2003;17:861.

    Google Scholar 

  220. Al-Waili N, Boni N. Natural honey lowers plasma prostaglandin concentrations in normal individuals.J Med Food. 2003;6:129–133.

    Article  PubMed  CAS  Google Scholar 

  221. Al-Waili N. Effect of honey on urinary prostaglandin and total nitrite.Int Nephrol Urol. 2005;37:107–111.

    Article  Google Scholar 

  222. Al-Waili NS, Boni NS. Honey increased saliva, plasma, and urine content of total nitrite concentrations in normal individuals.J Med Food. 2004;7:377–380.

    Article  PubMed  CAS  Google Scholar 

  223. Al-Waili N. Identification of nitric oxide metabolites in various honeys and effect of honey on plasma and urinary nitrite/nitrate concentrations.J Med Food. 2003;6:359–364.

    Article  PubMed  CAS  Google Scholar 

  224. Al-Waili N, Boni N. Increased nitric oxide production in saliva by natural honey.FASEB J. 2003;17:546.

    Google Scholar 

  225. Al-Waili N. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions.Med Sci Monit. 2004;10:94–98.

    Google Scholar 

  226. Al-Waili N, Saloom K. Honey to treat post-operative wound infections due to gram-positive and gram-negative bacteria following caesarian section and hysterectomies.Eur J Med Res. 1999;4:126–130.

    PubMed  CAS  Google Scholar 

  227. Al-Waili NS. Therapeutic and prophylactic effects of crude honey on chronic seborrheic dermatitis and dandruff.Eur J Med Res. 2001;6:306–308.

    PubMed  CAS  Google Scholar 

  228. Al-Waili N. Topical application of natural honey, beeswax and olive oil mixture to treat patients with atopic dermatitis or psoriasis.Compl Ther Med. 2003;11:226–234.

    Article  Google Scholar 

  229. Al-Waili N. Honey mixture with olive oil and beeswax for diaper dermatitis.Clin Microb Inf. 2005;11:160–163.

    Article  CAS  Google Scholar 

  230. Al-Waili NS, Haq A. Effect of honey on antibody production against thymus-dependent and thymus-independent antigens in primary and secondary immune responses.J Med Food. 2004;7:491–494.

    Article  PubMed  CAS  Google Scholar 

  231. Al-Waili N. Investigating the antimicrobial activity of natural honey and its effects on the pathogenic bacterial infections of surgical wounds and conjunctiva.J Med Food. 2004;7:210–222.

    Article  PubMed  CAS  Google Scholar 

  232. Al-Waili N. Effect of natural honey on chronic hepatitis B infection: case report.FASEB J. 2004;18:381.

    Google Scholar 

  233. Al-Waili S, Al-Waili T, Al-Waili A, Saloom K. Influence of natural honey on biochemical and hematological variables in AIDS: a case study.TSW Holistic Health Med. 2006;1:21–25.

    Article  Google Scholar 

  234. Al-Waili N, Saloom K, Al-Waili T, Al-Waili A. The safety and efficacy of a mixture of honey, olive oil and beeswax for the management of hemorrhoids and anal fissure: a pilot study.TSW Holistic Health Med. 2006;1:26–33.

    Article  Google Scholar 

  235. Al-Waili NS, Akmal M, Al-Waili FS, Saloom KY, Ali A. The antimicrobial potential of honey from United Arab Emirates on some microbial isolates.Med Sci Monit. 2005;11:433–438.

    Google Scholar 

  236. Al-Waili N, Saloom K, Al-Waili T, et al. Influence of various diet regimens on deterioration of hepatic function and hematological parameters following carbon tetrachloride: a potential protective role of natural honey.Nat Food Product. 2006;20):1258–64

    Google Scholar 

  237. Al-Waili N, Saloom K, Al-Waili T, et al. Honey ameliorates influences of hemorrhage and carbon tetrachloride administration on renal and hepatic functions, and hematological and biochemical variables.Int J Food Res Nutr. 2006;57:353–62

    Article  CAS  Google Scholar 

  238. Malone W, Kelloff G, Pierson H, Greenwald P. Chemoprevention of bladder cancer.Cancer. 1987;60(3 suppl):650–657.

    Article  PubMed  CAS  Google Scholar 

  239. Garay CA, Engstrom PF. Chemoprevention of colorectal cancer: dietary and pharmacologic approaches.Oncology (Williston Park). 1999;13:89–97.

    CAS  Google Scholar 

  240. el-Attar TM, Lin HS. In vitro inhibition of prostaglandin biosynthesis in squamous cell carcinoma by retinoids.Eicosanoids. 1990;3:95–98.

    CAS  Google Scholar 

  241. Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities.Curr Pharm Des. 2004;10:3813–3833.

    Article  PubMed  CAS  Google Scholar 

  242. Nakahata N, Kyo R, Kutsuwa M, Ohizumi Y. Inhibition of mitogen-activated protein kinase cas-cade by baicalein, a flavonoid of natural origin.Nippon Yakurigaku Zasshi. 1999;114(suppl 1):215P-219P.

    PubMed  Google Scholar 

  243. Park EJ, Min HY, Ahn YH, Bae CM, Pyee JH, Lee SK. Synthesis and inhibitory effects of pinosylvin derivatives on prostaglandin E2 production in lipopolysaccharide-induced mouse macrophage cells.Bioorg Med Chem Lett. 2004;14:5895–5898.

    Article  PubMed  CAS  Google Scholar 

  244. Gerhauser C, Alt A, Heiss E, et al. Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop.Mol Cancer Ther. 2002;1:959–969.

    PubMed  CAS  Google Scholar 

  245. Cho H, Yun CW, Park WK, et al. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysene derivatives.Pharmacol Res. 2004;49:37–43.

    Article  PubMed  CAS  Google Scholar 

  246. Nam KW, Je KH, Lee JH, et al. Inhibition of COX-2 activity and proinflammatory cytokines (TNF-alpha and IL-1beta) production by water-soluble sub-fractionated parts from bee (Apis mellifera) venom.Arch Pharm Res. 2003;26:383–388.

    PubMed  CAS  Google Scholar 

  247. Ganafa AA, Socci RR, Eatman D, Silvestrov N, Abukhalaf IK, Bayorh MA. Effect of palm oil on oxidative stress-induced hypertension in Sprague-Dawley rats.Am J Hypertens. 2002;15:725–731.

    Article  PubMed  CAS  Google Scholar 

  248. Ringbom T, Huss U, Stenholm A, et al. COX-2 inhibitory effects of naturally occurring and modified fatty acids.J Nat Prod. 2001;64:745–749.

    Article  PubMed  CAS  Google Scholar 

  249. Srivastava KC. Aqueous extracts of onion, garlic and ginger inhibit platelet aggregation and alter arachidonic acid metabolism.Biomed Biochim Acta. 1984;43:S335-S346.

    PubMed  CAS  Google Scholar 

  250. Srivastava KC. Isolation and effects of some ginger components of platelet aggregation and eicosanoid biosynthesis.Prostaglandins Leukot Med. 1986;25:187–198.

    Article  PubMed  CAS  Google Scholar 

  251. Srivastava KC. Onion exerts antiaggregatory effects by altering arachidonic acid metabolism in platelets.Prostaglandins Leukot Med. 1986;24:43–50.

    Article  PubMed  CAS  Google Scholar 

  252. Bartoli R, Fernandez-Banares F, Navarro E, et al. Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.Gut. 2000;46:191–199.

    Article  PubMed  CAS  Google Scholar 

  253. Bartram HP, Gostner A, Scheppach W, et al. Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects.Gastroenterology. 1993;105:1317–1322.

    PubMed  CAS  Google Scholar 

  254. Sheng H, Shao J, Morrow JD. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.Cancer Res. 1998;58:362–366.

    PubMed  CAS  Google Scholar 

  255. Minoura T, Takata T, Sakaguchi M. Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats.Cancer Res. 1988;48:4790–4794.

    PubMed  CAS  Google Scholar 

  256. Rao CV, Simi B, Wynn TT. Modulating effect of amount and types of dietary fat on colonic mucosal phospholipase A2, phosphatidylinositol-specific phospholipase C activities, and cyclooxygenase metabolite formation during different stages of colon tumour promotion in male F344 rats.Cancer Res. 1996;56:532–537.

    PubMed  CAS  Google Scholar 

  257. Hillier K, Jewell R, Dorrell L, Smith CL. Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease.Gut. 1991;32:1151–1155.

    Article  PubMed  CAS  Google Scholar 

  258. al-Sereiti MR, Abu-Amer KM, Sen P. Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials.Indian J Exp Biol. 1999;37:124–130.

    PubMed  CAS  Google Scholar 

  259. Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects.Semin Arthritis Rheum. 2005;34:773–784.

    Article  PubMed  Google Scholar 

  260. Wang SR, Guo ZQ, Liao JZ. Experimental study on effects of 18 kinds of Chinese herbal medicine for synthesis of thromboxane A2 and PGI2.Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993;13:167–170.

    PubMed  CAS  Google Scholar 

  261. Chou CT, Chang SC. The inhibitory effect of common traditional anti-rheumatic herb formulas on prostaglandin E and interleukin 2 in vitro: a comparative study with Tripterygium wilfordii.J Ethnopharmacol. 1998;62:167–171.

    Article  PubMed  CAS  Google Scholar 

  262. Fukutake M, Miura N, Yamamoto M, et al. Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.Cancer Lett. 2000;157:9–14.

    Article  PubMed  CAS  Google Scholar 

  263. Sengupta A, Ghosh S, Bhattacharjee S, Das S. Indian food ingredients and cancer prevention—an experimental evaluation of anticarcinogenic effects of garlic in rat colon.Asian Pac J Cancer Prev. 2004;5:126–132.

    PubMed  Google Scholar 

  264. Sengupta A, Ghosh S, Das S. Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat.Cancer Lett. 2004;208:127–136.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Al-Waili’s Charitable Foundation for Science and Trading, New York City, NY

    Noori S. Al-Waili MD, PhD, CHT, DOG, Khelod Y. Saloom BSc, MD, Thia Al-Waili, Ali Al-Waili & Hamza Al-Waili

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  1. Noori S. Al-Waili MD, PhD, CHT, DOG
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  2. Khelod Y. Saloom BSc, MD
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  3. Thia Al-Waili
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  5. Hamza Al-Waili
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Correspondence to Noori S. Al-Waili MD, PhD, CHT, DOG.

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Al-Waili, N.S., Saloom, K.Y., Al-Waili, T. et al. Modulation of prostaglandin activity, part 1: Prostaglandin inhibition in the management of nonrheumatologic diseases: Immunologic and hematologic aspects. Adv Therapy 24, 189–222 (2007). https://doi.org/10.1007/BF02850008

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