Skip to main content
SpringerLink
Log in

Pharmacologic Interventions with NSAIDs

  • Chapter
  • First Online:
Obesity, Inflammation and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 7))

  • 1766 Accesses

Abstract

Obesity as a determinant of increased cancer risk and poorer cancer outcome is well established for cancers of several organ sites, including colorectal and postmenopausal breast cancer. Obesity-associated adipose inflammation leads to local and systemic accumulation of inflammatory mediators and hormones, which have multiple proneoplastic effects. Key among these from a pharmacological perspective are cyclooxygenase (COX)-derived prostaglandins (PGs), since COX enzymes are the primary target for nonsteroidal anti-inflammatory drugs (NSAIDs). Overexpression of the inducible PG synthase COX-2 occurs in the majority of colorectal neoplasias and ~40 % of breast cancers and is also evident in inflamed adipose tissue from obese mice and humans. COX/PG signaling has multiple protumorigenic consequences, which provide at least a partial explanation for epidemiologic and experimental observations of reduced cancer risk associated with NSAID use. Notably, COX/PG-mediated upregulation of estrogen biosynthesis and signaling offers a plausible target for NSAID-mediated risk reduction with respect to breast and other hormone-sensitive cancers. Additionally, “off-target” NSAID effects including modulation of NFκB and AMP kinase activity may be of particular significance in the context of obesity. NSAID-mediated amelioration of obesity-­related metabolic dysfunction has been reported, and it seems likely that NSAIDs will be similarly protective for obesity-associated carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Calle EE, Thun MJ (2004) Obesity and cancer. Oncogene 23(38):6365–6378. doi:10.1038/sj.onc.1207751 1207751 [pii]

    PubMed  CAS  Google Scholar 

  2. Wolin KY, Carson K, Colditz GA (2010) Obesity and cancer. Oncologist 15(6):556–565. doi:theoncologist.2009-0285 [pii] 10.1634/theoncologist.2009-0285

    PubMed  Google Scholar 

  3. World Cancer Research Fund/American Institute for Cancer Research (2007) Food nutrition, physical activity, and the prevention of cancer: a global perspective. World Cancer Research Fund/American Institute for Cancer Research, Washington, DC

    Google Scholar 

  4. Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18(3):363–374. doi:nm.2627 [pii] 10.1038/nm.2627

    PubMed  CAS  Google Scholar 

  5. van Kruijsdijk RC, van der Wall E, Visseren FL (2009) Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev 18(10):2569–2578. doi:1055–9965.EPI-09-0372 [pii] 10.1158/1055-9965.EPI-09-0372

    PubMed  Google Scholar 

  6. Smith WL, Urade Y, Jakobsson PJ (2011) Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev 111(10):5821–5865. doi:10.1021/cr2002992

    PubMed  CAS  Google Scholar 

  7. Herschman HR (1996) Prostaglandin synthase 2. Biochim Biophys Acta 1299(1):125–140

    PubMed  Google Scholar 

  8. Brown JR, DuBois RN (2005) COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol 23(12):2840–2855. doi:23/12/2840 [pii] 10.1200/JCO.2005.09.051

    PubMed  CAS  Google Scholar 

  9. Howe LR, Subbaramaiah K, Brown AMC, Dannenberg AJ (2001) Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8(2):97–114

    PubMed  CAS  Google Scholar 

  10. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107(4):1183–1188

    PubMed  CAS  Google Scholar 

  11. Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S (1995) Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 55(12):2556–2559

    PubMed  CAS  Google Scholar 

  12. Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T (1995) Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55(17):3785–3789

    PubMed  CAS  Google Scholar 

  13. Kutchera W, Jones DA, Matsunami N, Groden J, McIntyre TM, Zimmerman GA, White RL, Prescott SM (1996) Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc Natl Acad Sci U S A 93(10):4816–4820

    PubMed  CAS  Google Scholar 

  14. Boolbol SK, Dannenberg AJ, Chadburn A, Martucci C, Guo XJ, Ramonetti JT, Abreu-Goris M, Newmark HL, Lipkin ML, DeCosse JJ, Bertagnolli MM (1996) Cyclooxygenase-2 ­overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 56(11):2556–2560

    PubMed  CAS  Google Scholar 

  15. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM (1996) Suppression of intestinal polyposis in Apc∆716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87(5):803–809

    PubMed  CAS  Google Scholar 

  16. Williams CS, Luongo C, Radhika A, Zhang T, Lamps LW, Nanney LB, Beauchamp RD, DuBois RN (1996) Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology 111(4):1134–1140

    PubMed  CAS  Google Scholar 

  17. DuBois RN, Radhika A, Reddy BS, Entingh AJ (1996) Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology 110(4):1259–1262

    PubMed  CAS  Google Scholar 

  18. Singh J, Hamid R, Reddy BS (1997) Dietary fat and colon cancer: modulation of cyclooxygenase-­2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res 57(16):3465–3470

    PubMed  CAS  Google Scholar 

  19. Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL, Hull MA (2000) Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156(2):545–553. doi:S0002-­9440(10)64759-1 [pii] 10.1016/S0002-9440(10)64759-1

    PubMed  CAS  Google Scholar 

  20. Hull MA, Booth JK, Tisbury A, Scott N, Bonifer C, Markham AF, Coletta PL (1999) Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice. Br J Cancer 79(9–10):1399–1405. doi:10.1038/sj.bjc.6690224

    PubMed  CAS  Google Scholar 

  21. Martinez ME, Heddens D, Earnest DL, Bogert CL, Roe D, Einspahr J, Marshall JR, Alberts DS (1999) Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa. J Natl Cancer Inst 91(11):950–953

    PubMed  CAS  Google Scholar 

  22. Bennett A, Charlier EM, McDonald AM, Simpson JS, Stamford IF, Zebro T (1977) Prostaglandins and breast cancer. Lancet 2(8039):624–626. doi:S0140-6736(77)92496-5 [pii]

    PubMed  CAS  Google Scholar 

  23. Rolland PH, Martin PM, Jacquemier J, Rolland AM, Toga M (1980) Prostaglandin in human breast cancer: evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 64(5):1061–1070

    PubMed  CAS  Google Scholar 

  24. Tan WC, Privett OS, Goldyne ME (1974) Studies of prostaglandins in rat mammary tumors induced by 7,12- dimethylbenz(a)anthracene. Cancer Res 34(12):3229–3231

    PubMed  CAS  Google Scholar 

  25. Boland GP, Butt IS, Prasad R, Knox WF, Bundred NJ (2004) COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. Br J Cancer 90(2):423–429

    PubMed  CAS  Google Scholar 

  26. Costa C, Soares R, Reis-Filho JS, Leitao D, Amendoeira I, Schmitt FC (2002) Cyclo-­oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol 55(6):429–434

    PubMed  CAS  Google Scholar 

  27. Davies G, Salter J, Hills M, Martin LA, Sacks N, Dowsett M (2003) Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer. Clin Cancer Res 9(7):2651–2656

    PubMed  CAS  Google Scholar 

  28. Denkert C, Winzer KJ, Muller BM, Weichert W, Pest S, Kobel M, Kristiansen G, Reles A, Siegert A, Guski H, Hauptmann S (2003) Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer 97(12):2978–2987

    PubMed  CAS  Google Scholar 

  29. Half E, Tang XM, Gwyn K, Sahin A, Wathen K, Sinicrope FA (2002) Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 62(6):1676–1681

    PubMed  CAS  Google Scholar 

  30. Kelly LM, Hill AD, Kennedy S, Connolly EM, Ramanath R, Teh S, Dijkstra B, Purcell R, McDermott EW, O’Higgins N (2003) Lack of prognostic effect of Cox-2 expression in primary breast cancer on short-term follow-up. Eur J Surg Oncol 29(9):707–710

    PubMed  CAS  Google Scholar 

  31. Lim SC (2003) Role of COX-2, VEGF and cyclin D1 in mammary infiltrating duct carcinoma. Oncol Rep 10(5):1241–1249

    PubMed  CAS  Google Scholar 

  32. Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62(3):632–635

    PubMed  CAS  Google Scholar 

  33. Shim JY, An HJ, Lee YH, Kim SK, Lee KP, Lee KS (2003) Overexpression of cyclooxygenase-­2 is associated with breast carcinoma and its poor prognostic factors. Mod Pathol 16(12):1199–1204

    PubMed  Google Scholar 

  34. Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, Koki AT (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89(12):2637–2645

    PubMed  CAS  Google Scholar 

  35. Spizzo G, Gastl G, Wolf D, Gunsilius E, Steurer M, Fong D, Amberger A, Margreiter R, Obrist P (2003) Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival. Br J Cancer 88(4):574–578

    PubMed  CAS  Google Scholar 

  36. Watanabe O, Shimizu T, Imamura H, Kinoshita J, Utada Y, Okabe T, Kimura K, Hirano A, Yoshimatsu K, Aiba M, Ogawa K (2003) Expression of cyclooxygenase-2 in malignant and benign breast tumors. Anticancer Res 23(4):3215–3221

    PubMed  CAS  Google Scholar 

  37. Wulfing P, Diallo R, Muller C, Wulfing C, Poremba C, Heinecke A, Rody A, Greb RR, Bocker W, Kiesel L (2003) Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis. J Cancer Res Clin Oncol 129(7):375–382

    PubMed  Google Scholar 

  38. Yoshimura N, Sano H, Okamoto M, Akioka K, Ushigome H, Kadotani Y, Yoshimura R, Nobori S, Higuchi A, Ohmori Y, Nakamura K (2003) Expression of cyclooxygenase-1 and -2 in human breast cancer. Surg Today 33(11):805–811

    PubMed  CAS  Google Scholar 

  39. Shim V, Gauthier ML, Sudilovsky D, Mantei K, Chew KL, Moore DH, Cha I, Tlsty TD, Esserman LJ (2003) Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium. Cancer Res 63(10):2347–2350

    PubMed  CAS  Google Scholar 

  40. Tan KB, Yong WP, Putti TC (2004) Cyclooxygenase-2 expression: a potential prognostic and predictive marker for high-grade ductal carcinoma in situ of the breast. Histopathology 44(1):24–28

    PubMed  Google Scholar 

  41. Kirkpatrick K, Ogunkolade W, Elkak A, Bustin S, Jenkins P, Ghilchik M, Mokbel K (2002) The mRNA expression of cyclo-oxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human breast cancer. Curr Med Res Opin 18(4):237–241

    PubMed  CAS  Google Scholar 

  42. Crawford YG, Gauthier ML, Joubel A, Mantei K, Kozakiewicz K, Afshari CA, Tlsty TD (2004) Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell 5(3):263–273

    PubMed  CAS  Google Scholar 

  43. Yang WT, Lewis MT, Hess K, Wong H, Tsimelzon A, Karadag N, Cairo M, Wei C, Meric-­Bernstam F, Brown P, Arun B, Hortobagyi GN, Sahin A, Chang JC (2010) Decreased TGFbeta signaling and increased COX2 expression in high risk women with increased mammographic breast density. Breast Cancer Res Treat 119(2):305–314. doi:10.1007/s10549-009-0350-0

    PubMed  CAS  Google Scholar 

  44. Holmes MD, Chen WY, Schnitt SJ, Collins L, Colditz GA, Hankinson SE, Tamimi RM (2011) COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat 130(2):657–662. doi:10.1007/s10549-011-1651-7

    PubMed  CAS  Google Scholar 

  45. Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD (2010) Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 102(9):627–637. doi:djq101 [pii] 10.1093/jnci/djq101

    PubMed  CAS  Google Scholar 

  46. Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ (2002) Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer. Evidence for involvement of AP-1 and PEA3. J Biol Chem 277:18649–18657

    PubMed  CAS  Google Scholar 

  47. Badawi AF, el-Sohemy A, Stephen LL, Ghoshal AK, Archer MC (1999) Modulation of the expression of the cyclooxygenase 1 and 2 genes in rat mammary glands: role of hormonal status and dietary fat. Adv Exp Med Biol 469:119–124

    PubMed  CAS  Google Scholar 

  48. Hamid R, Singh J, Reddy BS, Cohen LA (1999) Inhibition by dietary menhaden oil of cyclooxygenase-­1 and -2 in N-nitrosomethylurea-induced rat mammary tumors. Int J Oncol 14(3):523–528

    PubMed  CAS  Google Scholar 

  49. Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ, Brown AMC (2001) PEA3 is upregulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276(23):20108–20115

    PubMed  CAS  Google Scholar 

  50. Howe LR, Subbaramaiah K, Patel J, Masferrer JL, Deora A, Hudis C, Thaler HT, Muller WJ, Du B, Brown AMC, Dannenberg AJ (2002) Celecoxib, a selective cyclooxygenase-2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res 62:5405–5407

    PubMed  CAS  Google Scholar 

  51. Nakatsugi S, Ohta T, Kawamori T, Mutoh M, Tanigawa T, Watanabe K, Sugie S, Sugimura T, Wakabayashi K (2000) Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland carcinogenesis in rats. Jpn J Cancer Res 91(9):886–892

    PubMed  CAS  Google Scholar 

  52. Robertson FM, Parrett ML, Joarder FS, Ross M, Abou-Issa HM, Alshafie G, Harris RE (1998) Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas. Cancer Lett 122(1–2):165–175

    PubMed  CAS  Google Scholar 

  53. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P, Kopelovich L, Hudis CA, Dannenberg AJ (2011) Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila) 4(3):329–346. doi:4/3/329 [pii] 10.1158/1940-6207.CAPR-10-0381

    CAS  Google Scholar 

  54. Subbaramaiah K, Morris PG, Zhou XK, Morrow M, Du B, Giri D, Kopelovich L, Hudis CA, Dannenberg AJ (2012) Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov 2(4):356–365. doi:2159–8290.CD-11-0241 [pii] 10.1158/2159-8290.CD-11-0241

    PubMed  CAS  Google Scholar 

  55. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54(8):2277–2286. doi:54/8/2277 [pii]

    PubMed  CAS  Google Scholar 

  56. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46(11):2347–2355. doi:M500294-JLR200 [pii] 10.1194/jlr.M500294-JLR200

    PubMed  CAS  Google Scholar 

  57. Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, Cinti S (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49(7):1562–1568. doi:M800019-JLR200 [pii] 10.1194/jlr.M800019-JLR200

    PubMed  CAS  Google Scholar 

  58. Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, Du B, Brogi E, Crawford CB, Kopelovich L, Subbaramaiah K, Dannenberg AJ (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila) 4(7):1021–1029. doi:1940–6207.CAPR-11-0110 [pii] 10.1158/1940-6207.CAPR-11-0110

    CAS  Google Scholar 

  59. Sun X, Casbas-Hernandez P, Bigelow C, Makowski L, Joseph Jerry D, Smith Schneider S, Troester MA (2012) Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression. Breast Cancer Res Treat 131(3):1003–1012. doi:10.1007/s10549-011-1789-3 [doi]

    PubMed  CAS  Google Scholar 

  60. Howe LR, Chang SH, Tolle KC, Dillon R, Young LJT, Cardiff RD, Newman RA, Yang P, Thaler HT, Muller WJ, Hudis C, Brown AMC, Hla T, Subbaramaiah K, Dannenberg AJ (2005) HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-­2 knockout mice. Cancer Res 65(21):10113–10119

    PubMed  CAS  Google Scholar 

  61. Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW, Lee C, Tiano HF, Morham SG, Smithies O, Langenbach R (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60(17):4705–4708

    PubMed  CAS  Google Scholar 

  62. Tiano HF, Loftin CD, Akunda J, Lee CA, Spalding J, Sessoms A, Dunson DB, Rogan EG, Morham SG, Smart RC, Langenbach R (2002) Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res 62(12):3395–3401

    PubMed  CAS  Google Scholar 

  63. Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF, Hla T (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276:18563–18569

    PubMed  CAS  Google Scholar 

  64. Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T (2004) Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci U S A 101(2):591–596

    PubMed  CAS  Google Scholar 

  65. Muller-Decker K, Neufang G, Berger I, Neumann M, Marks F, Furstenberger G (2002) Transgenic cyclooxygenase-2 overexpression sensitizes mouse skin for carcinogenesis. Proc Natl Acad Sci U S A 99(19):12483–12488

    PubMed  CAS  Google Scholar 

  66. Wang D, Dubois RN (2006) Prostaglandins and cancer. Gut 55(1):115–122. doi:gut.2004.047100 [pii] 10.1136/gut.2004.047100

    PubMed  CAS  Google Scholar 

  67. Nakanishi M, Montrose DC, Clark P, Nambiar PR, Belinsky GS, Claffey KP, Xu D, Rosenberg DW (2008) Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res 68(9):3251–3259. doi:68/9/3251 [pii] 10.1158/0008-5472.CAN-07-6100

    PubMed  CAS  Google Scholar 

  68. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:S0092-8674(11)00127-9 [pii] 10.1016/j.cell.2011.02.013

    PubMed  CAS  Google Scholar 

  69. Bandyopadhyay GK, Imagawa W, Wallace D, Nandi S (1987) Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor. J Biol Chem 262(6):2750–2756

    PubMed  CAS  Google Scholar 

  70. Goin M, Pignataro O, Jimenez de Asua L (1993) Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells. FEBS Lett 316(1):68–72

    PubMed  CAS  Google Scholar 

  71. Nolan RD, Danilowicz RM, Eling TE (1988) Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. Mol Pharmacol 33(6):650–656

    PubMed  CAS  Google Scholar 

  72. Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30(3):377–386. doi:bgp014 [pii] 10.1093/carcin/bgp014

    PubMed  CAS  Google Scholar 

  73. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, Fitzgerald GA, Daley GQ, Orkin SH, Zon LI (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447(7147):1007–1011. doi:nature05883 [pii] 10.1038/nature05883

    PubMed  CAS  Google Scholar 

  74. Li HJ, Reinhardt F, Herschman HR, Weinberg RA (2012) Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov 2(9):840–855. doi:2159–8290.CD-12-0101 [pii] 10.1158/2159-8290.CD-12-0101

    PubMed  CAS  Google Scholar 

  75. Rudnick JA, Arendt LM, Klebba I, Hinds JW, Iyer V, Gupta PB, Naber SP, Kuperwasser C (2011) Functional heterogeneity of breast fibroblasts is defined by a prostaglandin secretory phenotype that promotes expansion of cancer-stem like cells. PLoS One 6(9):e24605. doi:10.1371/journal.pone.0024605 PONE-D-11-11675 [pii]

    PubMed  CAS  Google Scholar 

  76. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310(5753):1504–1510. doi:1116221 [pii] 10.1126/science.1116221

    PubMed  CAS  Google Scholar 

  77. Buchanan FG, Wang D, Bargiacchi F, DuBois RN (2003) Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278(37):35451–35457. doi:10.1074/jbc.M302474200 M302474200 [pii]

    PubMed  CAS  Google Scholar 

  78. Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8(3):289–293. doi:10.1038/nm0302-289 nm0302-289 [pii]

    PubMed  CAS  Google Scholar 

  79. Ben-Baruch A (2006) Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 16(1):38–52. doi:S1044-579X(05)00059-3 [pii] 10.1016/j.semcancer.2005.07.006

    PubMed  CAS  Google Scholar 

  80. Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182(8):4499–4506. doi:182/8/4499 [pii] 10.4049/jimmunol.0802740

    PubMed  CAS  Google Scholar 

  81. Chen EP, Smyth EM (2011) COX-2 and PGE2-dependent immunomodulation in breast cancer. Prostaglandins Other Lipid Mediat 96(1–4):14–20. doi:S1098-8823(11)00075-X [pii] 10.1016/j.prostaglandins.2011.08.005

    PubMed  CAS  Google Scholar 

  82. Strassmann G, Patil-Koota V, Finkelman F, Fong M, Kambayashi T (1994) Evidence for the involvement of interleukin 10 in the differential deactivation of murine peritoneal macrophages by prostaglandin E2. J Exp Med 180(6):2365–2370

    PubMed  CAS  Google Scholar 

  83. Markosyan N, Chen EP, Ndong VN, Yao Y, Sterner CJ, Chodosh LA, Lawson JA, Fitzgerald GA, Smyth EM (2011) Deletion of cyclooxygenase 2 in mouse mammary epithelial cells delays breast cancer onset through augmentation of type 1 immune responses in tumors. Carcinogenesis 32(10):1441–1449. doi:bgr134 [pii] 10.1093/carcin/bgr134

    PubMed  CAS  Google Scholar 

  84. Balkwill FR, Mantovani A (2012) Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol 22(1):33–40. doi:S1044-579X(11)00106-4 [pii] 10.1016/j.semcancer.2011.12.005

    PubMed  CAS  Google Scholar 

  85. Sombroek CC, Stam AG, Masterson AJ, Lougheed SM, Schakel MJ, Meijer CJ, Pinedo HM, van den Eertwegh AJ, Scheper RJ, de Gruijl TD (2002) Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol 168(9):4333–4343

    PubMed  CAS  Google Scholar 

  86. Stolina M, Sharma S, Zhu L, Dubinett SM (2000) Lung cancer cyclooxygenase-2 dependent inhibition of dendritic cells maturation and function. Proc Am Assoc Cancer Res 41:619

    Google Scholar 

  87. Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83(3):493–501

    PubMed  CAS  Google Scholar 

  88. Takahashi Y, Kawahara F, Noguchi M, Miwa K, Sato H, Seiki M, Inoue H, Tanabe T, Yoshimoto T (1999) Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2. FEBS Lett 460(1):145–148

    PubMed  CAS  Google Scholar 

  89. Tsujii M, Kawano S, DuBois RN (1997) Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A 94(7):3336–3340

    PubMed  CAS  Google Scholar 

  90. Connolly EM, Harmey JH, O’Grady T, Foley D, Roche-Nagle G, Kay E, Bouchier-Hayes DJ (2002) Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer. Br J Cancer 87(2):231–237

    PubMed  CAS  Google Scholar 

  91. Kundu N, Fulton AM (2002) Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease in a murine model of breast cancer. Cancer Res 62(8):2343–2346

    PubMed  CAS  Google Scholar 

  92. Roche-Nagle G, Connolly EM, Eng M, Bouchier-Hayes DJ, Harmey JH (2004) Antimetastatic activity of a cyclooxygenase-2 inhibitor. Br J Cancer 91(2):359–365

    PubMed  CAS  Google Scholar 

  93. Miyaura C, Inada M, Suzawa T, Sugimoto Y, Ushikubi F, Ichikawa A, Narumiya S, Suda T (2000) Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-­knockout mice. J Biol Chem 275(26):19819–19823

    PubMed  CAS  Google Scholar 

  94. Okada Y, Lorenzo JA, Freeman AM, Tomita M, Morham SG, Raisz LG, Pilbeam CC (2000) Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture. J Clin Invest 105(6):823–832

    PubMed  CAS  Google Scholar 

  95. Ono K, Akatsu T, Murakami T, Nishikawa M, Yamamoto M, Kugai N, Motoyoshi K, Nagata N (1998) Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2. J Endocrinol 158(3):R1–R5

    PubMed  CAS  Google Scholar 

  96. Sabino MA, Ghilardi JR, Jongen JL, Keyser CP, Luger NM, Mach DB, Peters CM, Rogers SD, Schwei MJ, de Felipe C, Mantyh PW (2002) Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res 62(24):7343–7349

    PubMed  CAS  Google Scholar 

  97. Powles TJ, Dowsett M, Easty GC, Easty DM, Neville AM (1976) Breast-cancer osteolysis, bone metastases, and anti-osteolytic effect of aspirin. Lancet 1(7960):608–610. doi:S0140-­6736(76)90416-5 [pii]

    PubMed  CAS  Google Scholar 

  98. Seno H, Oshima M, Ishikawa TO, Oshima H, Takaku K, Chiba T, Narumiya S, Taketo MM (2002) Cyclooxygenase 2- and prostaglandin E2 receptor EP2-dependent angiogenesis in Apc∆716 mouse intestinal polyps. Cancer Res 62(2):506–511

    PubMed  CAS  Google Scholar 

  99. Takeda H, Sonoshita M, Oshima H, Sugihara K, Chulada PC, Langenbach R, Oshima M, Taketo MM (2003) Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Cancer Res 63(16):4872–4877

    PubMed  CAS  Google Scholar 

  100. Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN (2000) Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105(11):1589–1594

    PubMed  CAS  Google Scholar 

  101. Peterson HI (1983) Effects of prostaglandin synthesis inhibitors on tumor growth and vascularization. Experimental studies in the rat. Invasion Metastasis 3(3):151–159

    PubMed  CAS  Google Scholar 

  102. Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ (1999) Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res 59(18):4574–4577

    PubMed  CAS  Google Scholar 

  103. Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL (2002) Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 62(3):625–631

    PubMed  CAS  Google Scholar 

  104. Majima M, Isono M, Ikeda Y, Hayashi I, Hatanaka K, Harada Y, Katsumata O, Yamashina S, Katori M, Yamamoto S (1997) Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants. Jpn J Pharmacol 75(2):105–114

    PubMed  CAS  Google Scholar 

  105. Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K (2000) Antiangiogenic and antitumor activities of cyclooxygenase-­2 inhibitors. Cancer Res 60(5):1306–1311

    PubMed  CAS  Google Scholar 

  106. Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M (1999) Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 79(12):1469–1477

    PubMed  CAS  Google Scholar 

  107. Yamada M, Kawai M, Kawai Y, Mashima Y (1999) The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat. Curr Eye Res 19(4):300–304

    PubMed  CAS  Google Scholar 

  108. Jones MK, Wang H, Peskar BM, Levin E, Itani RM, Sarfeh IJ, Tarnawski AS (1999) Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 5(12):1418–1423

    PubMed  CAS  Google Scholar 

  109. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5):705–716. doi:S0092-­8674(00)81433-6 [pii]

    PubMed  CAS  Google Scholar 

  110. Gately S, Li WW (2004) Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy. Semin Oncol 31(2 suppl 7):2–11

    PubMed  CAS  Google Scholar 

  111. Leahy KM, Koki AT, Masferrer JL (2000) Role of cyclooxygenases in angiogenesis. Curr Med Chem 7(11):1163–1170

    PubMed  CAS  Google Scholar 

  112. Miyazawa-Hoshimoto S, Takahashi K, Bujo H, Hashimoto N, Saito Y (2003) Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects. Diabetologia 46(11):1483–1488

    PubMed  CAS  Google Scholar 

  113. Garcia de la Torre N, Rubio MA, Bordiu E, Cabrerizo L, Aparicio E, Hernandez C, Sanchez-­Pernaute A, Diez-Valladares L, Torres AJ, Puente M, Charro AL (2008) Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines, and insulin. J Clin Endocrinol Metab 93(11):4276–4281. doi:jc.2007-1370 [pii] 10.1210/jc.2007-1370

    PubMed  CAS  Google Scholar 

  114. Silha JV, Krsek M, Sucharda P, Murphy LJ (2005) Angiogenic factors are elevated in overweight and obese individuals. Int J Obes (Lond) 29(11):1308–1314. doi:0802987 [pii] 10.1038/sj.ijo.0802987

    CAS  Google Scholar 

  115. Gu JW, Young E, Patterson SG, Makey KL, Wells J, Huang M, Tucker KB, Miele L (2011) Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice. Cancer Biol Ther 11(10):910–917. doi:15473 [pii]

    PubMed  CAS  Google Scholar 

  116. Chen CT, Du Y, Yamaguchi H, Hsu JM, Kuo HP, Hortobagyi GN, Hung MC (2012) Targeting the IKKbeta/mTOR/VEGF signaling pathway as a potential therapeutic strategy for obesity-­related breast cancer. Mol Cancer Ther 11(10):2212–2221. doi:1535–7163.MCT-12-0180 [pii] 10.1158/1535-7163.MCT-12-0180

    PubMed  CAS  Google Scholar 

  117. Barnes NL, Warnberg F, Farnie G, White D, Jiang W, Anderson E, Bundred NJ (2007) Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. Br J Cancer 96(4):575–582. doi:6603593 [pii] 10.1038/sj.bjc.6603593

    PubMed  CAS  Google Scholar 

  118. Timoshenko AV, Chakraborty C, Wagner GF, Lala PK (2006) COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. Br J Cancer 94(8):1154–1163. doi:6603593 [pii] 10.1038/sj.bjc.6603593

    PubMed  CAS  Google Scholar 

  119. Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones M (2002) Aromatase—a brief overview. Annu Rev Physiol 64:93–127. doi:10.1146/annurev.physiol.64.081601.142703 64/1/93 [pii]

    PubMed  CAS  Google Scholar 

  120. Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER (1993) A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab 77(6):1622–1628

    PubMed  CAS  Google Scholar 

  121. Lipton A, Santen RJ, Santner SJ, Harvey HA, Sanders SI, Matthews YL (1992) Prognostic value of breast cancer aromatase. Cancer 70(7):1951–1955

    PubMed  CAS  Google Scholar 

  122. Miller WR, Anderson TJ, Jack WJ (1990) Relationship between tumour aromatase activity, tumour characteristics and response to therapy. J Steroid Biochem Mol Biol 37(6):1055–1059

    PubMed  CAS  Google Scholar 

  123. Silva MC, Rowlands MG, Dowsett M, Gusterson B, McKinna JA, Fryatt I, Coombes RC (1989) Intratumoral aromatase as a prognostic factor in human breast carcinoma. Cancer Res 49(10):2588–2591

    PubMed  CAS  Google Scholar 

  124. Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER (1996) Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 81(11):3843–3849

    PubMed  CAS  Google Scholar 

  125. Chen S, Itoh T, Wu K, Zhou D, Yang C (2002) Transcriptional regulation of aromatase expression in human breast tissue. J Steroid Biochem Mol Biol 83(1–5):93–99

    PubMed  CAS  Google Scholar 

  126. Mahendroo MS, Mendelson CR, Simpson ER (1993) Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 268(26):19463–19470

    PubMed  CAS  Google Scholar 

  127. Zhou D, Chen S (1999) Identification and characterization of a cAMP-responsive element in the region upstream from promoter 1.3 of the human aromatase gene. Arch Biochem Biophys 371(2):179–190

    PubMed  CAS  Google Scholar 

  128. Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79(4):1193–1226

    PubMed  CAS  Google Scholar 

  129. Brueggemeier RW, Richards JA, Joomprabutra S, Bhat AS, Whetstone JL (2001) Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents. J Steroid Biochem Mol Biol 79(1–5):75–84

    PubMed  CAS  Google Scholar 

  130. Singh A, Purohit A, Ghilchik MW, Reed MJ (1999) The regulation of aromatase activity in breast fibroblasts: the role of interleukin-6 and prostaglandin E2. Endocr Relat Cancer 6(2):139–147

    PubMed  CAS  Google Scholar 

  131. Zhao Y, Agarwal VR, Mendelson CR, Simpson ER (1996) Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137(12):5739–5742

    PubMed  CAS  Google Scholar 

  132. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ (2008) EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange. J Biol Chem 283(6):3433–3444. doi:M705409200 [pii] ­10.1074/jbc.M705409200

    PubMed  CAS  Google Scholar 

  133. Prosperi JR, Robertson FM (2006) Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase promoter regions pII, pI.3 and pI.7 and estradiol production in human breast tumor cells. Prostaglandins Other Lipid Mediat 81(1–2):55–70. doi:S1098-­8823(06)00115-8 [pii] 10.1016/j.prostaglandins.2006.07.003

    PubMed  CAS  Google Scholar 

  134. Brodie AM, Lu Q, Long BJ, Fulton A, Chen T, Macpherson N, DeJong PC, Blankenstein MA, Nortier JW, Slee PH, van de Ven J, van Gorp JM, Elbers JR, Schipper ME, Blijham GH, Thijssen JH (2001) Aromatase and COX-2 expression in human breast cancers. J Steroid Biochem Mol Biol 79(1–5):41–47

    PubMed  CAS  Google Scholar 

  135. Brueggemeier RW, Quinn AL, Parrett ML, Joarder FS, Harris RE, Robertson FM (1999) Correlation of aromatase and cyclooxygenase gene expression in human breast cancer ­specimens. Cancer Lett 140(1–2):27–35

    PubMed  CAS  Google Scholar 

  136. Salhab M, Singh-Ranger G, Mokbel R, Jouhra F, Jiang WG, Mokbel K (2007) Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer. J Surg Oncol 96(5):424–428. doi:10.1002/jso.20740

    PubMed  CAS  Google Scholar 

  137. Subbaramaiah K, Howe LR, Port ER, Brogi E, Fishman J, Liu CH, Hla T, Hudis C, Dannenberg AJ (2006) HER-2/neu status is a determinant of mammary aromatase activity in vivo: evidence for a cyclooxygenase-2-dependent mechanism. Cancer Res 66(10):5504–5511. doi:66/10/5504 [pii] 10.1158/0008-5472.CAN-05-4076

    PubMed  CAS  Google Scholar 

  138. Gates MA, Tworoger SS, Eliassen AH, Missmer SA, Hankinson SE (2010) Analgesic use and sex steroid hormone concentrations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 19(4):1033–1041. doi:1055–9965.EPI-09-0975 [pii] 10.1158/1055-9965.EPI-09-0975

    PubMed  CAS  Google Scholar 

  139. Hudson AG, Gierach GL, Modugno F, Simpson J, Wilson JW, Evans RW, Vogel VG, Weissfeld JL (2008) Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17(3):680–687. doi:17/3/680 [pii] 10.1158/1055-9965.EPI-07-2739

    PubMed  CAS  Google Scholar 

  140. Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG (1989) The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol 129(6):1120–1131

    PubMed  CAS  Google Scholar 

  141. Kaye SA, Folsom AR, Soler JT, Prineas RJ, Potter JD (1991) Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol 20(1):151–156

    PubMed  CAS  Google Scholar 

  142. McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, Gilliland F, Stanczyk FZ, Yasui Y, Ballard-Barbash R (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 21(10):1961–1966. doi:10.1200/JCO.2003.07.057 JCO.2003.07.057 [pii]

    PubMed  CAS  Google Scholar 

  143. Wake DJ, Strand M, Rask E, Westerbacka J, Livingstone DE, Soderberg S, Andrew R, Yki-­Jarvinen H, Olsson T, Walker BR (2007) Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity. Clin Endocrinol (Oxf) 66(3):440–446. doi:CEN2755 [pii] 10.1111/j.1365-2265.2007.02755.x

    CAS  Google Scholar 

  144. Marnett LJ (1992) Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res 52(20):5575–5589

    PubMed  CAS  Google Scholar 

  145. Corpet DE, Pierre F (2003) Point: from animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system. Cancer Epidemiol Biomarkers Prev 12(5):391–400

    PubMed  Google Scholar 

  146. Rao CV, Reddy BS (2004) NSAIDs and chemoprevention. Curr Cancer Drug Targets 4(1):29–42

    PubMed  CAS  Google Scholar 

  147. Howe LR (2005) Cyclooxygenase-2 and breast cancer. In: Yao AP (ed) Trends in breast cancer research, vol 9, Horizons in cancer research. Nova, New York, pp 1–38

    Google Scholar 

  148. Buchanan FG, Holla V, Katkuri S, Matta P, DuBois RN (2007) Targeting cyclooxygenase-2 and the epidermal growth factor receptor for the prevention and treatment of intestinal cancer. Cancer Res 67(19):9380–9388. doi:67/19/9380 [pii] 10.1158/0008-5472.CAN-07-0710

    PubMed  CAS  Google Scholar 

  149. Torrance CJ, Jackson PE, Montgomery E, Kinzler KW, Vogelstein B, Wissner A, Nunes M, Frost P, Discafani CM (2000) Combinatorial chemoprevention of intestinal neoplasia. Nat Med 6(9):1024–1028. doi:10.1038/79534

    PubMed  CAS  Google Scholar 

  150. Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN (2001) Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 120(7):1713–1719

    PubMed  CAS  Google Scholar 

  151. Reddy BS, Patlolla JM, Simi B, Wang SH, Rao CV (2005) Prevention of colon cancer by low doses of celecoxib, a cyclooxygenase inhibitor, administered in diet rich in omega-3 polyunsaturated fatty acids. Cancer Res 65(17):8022–8027. doi:65/17/8022 [pii] 10.1158/0008-­5472.CAN-05-0212

    PubMed  CAS  Google Scholar 

  152. Reddy BS, Wang CX, Kong AN, Khor TO, Zheng X, Steele VE, Kopelovich L, Rao CV (2006) Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats. Cancer Res 66(8):4542–4546. doi:66/8/4542 [pii] 10.1158/0008-5472.CAN-05-4428

    PubMed  CAS  Google Scholar 

  153. Swamy MV, Patlolla JM, Steele VE, Kopelovich L, Reddy BS, Rao CV (2006) Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. Cancer Res 66(14):7370–7377. doi:66/14/7370 [pii] 10.1158/0008-5472.CAN-05-4619

    PubMed  CAS  Google Scholar 

  154. Ignatenko NA, Besselsen DG, Stringer DE, Blohm-Mangone KA, Cui H, Gerner EW (2008) Combination chemoprevention of intestinal carcinogenesis in a murine model of familial adenomatous polyposis. Nutr Cancer 60(suppl 1):30–35. doi:905311576 [pii] 10.1080/01635580802401317

    PubMed  Google Scholar 

  155. Lanza-Jacoby S, Miller S, Flynn J, Gallatig K, Daskalakis C, Masferrer JL, Zweifel BS, Sembhi H, Russo IH (2003) The cyclooxygenase-2 inhibitor, celecoxib, prevents the development of mammary tumors in Her-2/neu mice. Cancer Epidemiol Biomarkers Prev 12(12):1486–1491

    PubMed  CAS  Google Scholar 

  156. Woditschka S, Haag JD, Mau B, Lubet RA, Gould MN (2008) Chemopreventive effects of celecoxib are limited to hormonally responsive mammary carcinomas in the neu-induced retroviral rat model. Breast Cancer Res 10(1):R18. doi:bcr1864 [pii] 10.1186/bcr1864

    PubMed  Google Scholar 

  157. Brown PH, Subbaramaiah K, Salmon AP, Baker R, Newman RA, Yang P, Zhou XK, Bissonnette RP, Dannenberg AJ, Howe LR (2008) Combination chemoprevention of HER2/neu-induced breast cancer using a cyclooxygenase-2 inhibitor and a retinoid X receptor-­selective retinoid. Cancer Prev Res (Phila) 1(3):208–214. doi:1/3/208 [pii] 10.1158/1940-­6207.CAPR-08-0021

    CAS  Google Scholar 

  158. Chan AT, Arber N, Burn J, Chia WK, Elwood P, Hull MA, Logan RF, Rothwell PM, Schror K, Baron JA (2012) Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev Res (Phila) 5(2):164–178. doi:1940–6207.CAPR-11-0391 [pii] 10.1158/1940-­6207.CAPR-11-0391

    CAS  Google Scholar 

  159. Bosetti C, Rosato V, Gallus S, Cuzick J, La Vecchia C (2012) Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol 23(6):1403–1415. doi:mds113 [pii] 10.1093/annonc/mds113

    PubMed  CAS  Google Scholar 

  160. Reeves MJ, Newcomb PA, Trentham-Dietz A, Storer BE, Remington PL (1996) Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 5(12):955–960

    PubMed  CAS  Google Scholar 

  161. Rosenberg L, Louik C, Shapiro S (1998) Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma. Cancer 82(12):2326–2333. doi:10.1002/(SICI)1097-­0142(19980615)82:12<2326::AID-CNCR5>3.0.CO;2-Q [pii]

    PubMed  CAS  Google Scholar 

  162. Harris RE, Beebe-Donk J, Alshafie GA (2008) Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 8:237. doi:1471-2407-8-237 [pii] 10.1186/1471-2407-8-237

    PubMed  Google Scholar 

  163. Ruder EH, Laiyemo AO, Graubard BI, Hollenbeck AR, Schatzkin A, Cross AJ (2011) Non-­steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol 106(7):1340–1350. doi:ajg201138 [pii] 10.1038/ajg.2011.38

    PubMed  CAS  Google Scholar 

  164. Rahme E, Barkun AN, Toubouti Y, Bardou M (2003) The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology 125(2):404–412. doi:S0016508503008801 [pii]

    PubMed  CAS  Google Scholar 

  165. Vinogradova Y, Hippisley-Cox J, Coupland C, Logan RF (2007) Risk of colorectal cancer in patients prescribed statins, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitors: nested case–control study. Gastroenterology 133(2):393–402. doi:S0016-­5085(07)01005-0 [pii] 10.1053/j.gastro.2007.05.023

    PubMed  Google Scholar 

  166. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377(9759):31–41. doi:S0140-6736(10)62110-1 [pii] 10.1016/S0140-6736(10)62110-1

    PubMed  CAS  Google Scholar 

  167. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TW (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376(9754):1741–1750. doi:S0140-6736(10)61543-7 [pii] 10.1016/S0140-6736(10)61543-7

    PubMed  CAS  Google Scholar 

  168. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z (2012) Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 379(9826):1591–1601. doi:S0140-6736(12)60209-8 [pii] 10.1016/S0140-6736(12)60209-8

    PubMed  CAS  Google Scholar 

  169. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328(18):1313–1316

    PubMed  CAS  Google Scholar 

  170. Giardiello FM, Spannhake EW, DuBois RN, Hylind LM, Robinson CR, Hubbard WC, Hamilton SR, Yang VW (1998) Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis. Dig Dis Sci 43(2):311–316

    PubMed  CAS  Google Scholar 

  171. Meyskens FL Jr, McLaren CE, Pelot D, Fujikawa-Brooks S, Carpenter PM, Hawk E, Kelloff G, Lawson MJ, Kidao J, McCracken J, Albers CG, Ahnen DJ, Turgeon DK, Goldschmid S, Lance P, Hagedorn CH, Gillen DL, Gerner EW (2008) Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-­blind trial. Cancer Prev Res (Phila) 1(1):32–38. doi:10.1158/1940-6207.CAPR-08-0042

    CAS  Google Scholar 

  172. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348(10):891–899

    PubMed  CAS  Google Scholar 

  173. Logan RF, Grainge MJ, Shepherd VC, Armitage NC, Muir KR (2008) Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 134(1):29–38. doi:S0016-5085(07)01813-6 [pii] 10.1053/j.gastro.2007.10.014

    PubMed  CAS  Google Scholar 

  174. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348(10):883–890

    PubMed  CAS  Google Scholar 

  175. Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125(2):328–336. doi:S0016508503008874 [pii]

    PubMed  CAS  Google Scholar 

  176. Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, Chaussade S, Baron JA (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101(4):256–266. doi:djn485 [pii] 10.1093/jnci/djn485

    PubMed  CAS  Google Scholar 

  177. Benamouzig R, Uzzan B, Deyra J, Martin A, Girard B, Little J, Chaussade S (2012) Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial. Gut 61(2):255–261. doi:gutjnl-2011-300113 [pii] 10.1136/gutjnl-2011-300113

    PubMed  CAS  Google Scholar 

  178. Barnes CJ, Hamby-Mason RL, Hardman WE, Cameron IL, Speeg KV, Lee M (1999) Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon. Cancer Epidemiol Biomarkers Prev 8(4 pt 1):311–315

    PubMed  CAS  Google Scholar 

  179. Frommel TO, Dyavanapalli M, Oldham T, Kazi N, Lietz H, Liao Y, Mobarhan S (1997) Effect of aspirin on prostaglandin E2 and leukotriene B4 production in human colonic mucosa from cancer patients. Clin Cancer Res 3(2):209–213

    PubMed  CAS  Google Scholar 

  180. Krishnan K, Ruffin MT, Normolle D, Shureiqi I, Burney K, Bailey J, Peters-Golden M, Rock CL, Boland CR, Brenner DE (2001) Colonic mucosal prostaglandin E2 and cyclooxygenase expression before and after low aspirin doses in subjects at high risk or at normal risk for colorectal cancer. Cancer Epidemiol Biomarkers Prev 10(5):447–453

    PubMed  CAS  Google Scholar 

  181. Ruffin MT, Krishnan K, Rock CL, Normolle D, Vaerten MA, Peters-Golden M, Crowell J, Kelloff G, Boland CR, Brenner DE (1997) Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose. J Natl Cancer Inst 89(15):1152–1160

    PubMed  CAS  Google Scholar 

  182. Sample D, Wargovich M, Fischer SM, Inamdar N, Schwartz P, Wang X, Do KA, Sinicrope FA (2002) A dose-finding study of aspirin for chemoprevention utilizing rectal mucosal prostaglandin E(2) levels as a biomarker. Cancer Epidemiol Biomarkers Prev 11(3):275–279

    PubMed  CAS  Google Scholar 

  183. Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JW, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378(9809):2081–2087. doi:S0140-6736(11)61049-0 [pii] 10.1016/S0140-6736(11)61049-0

    PubMed  Google Scholar 

  184. Sturmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH (1998) Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians’ Health Study. Ann Intern Med 128(9):713–720

    PubMed  CAS  Google Scholar 

  185. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294(1):47–55. doi:294/1/47 [pii] 10.1001/jama.294.1.47

    PubMed  CAS  Google Scholar 

  186. Dube C, Rostom A, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146(5):365–375. doi:146/5/365 [pii]

    PubMed  Google Scholar 

  187. Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P, Jankowski J, La Vecchia C, Meyskens F, Senn HJ, Thun M (2009) Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 10(5):501–507. doi:S1470-2045(09)70035-X [pii] 10.1016/S1470-2045(09)70035-X

    PubMed  CAS  Google Scholar 

  188. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 294(8):914–923. doi:294/8/914 [pii] 10.1001/jama.294.8.914

    PubMed  CAS  Google Scholar 

  189. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Wu K, Fuchs CS (2008) Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology 134(1):21–28. doi:S0016-5085(07)01745-3 [pii] 10.1053/j.gastro.2007.09.035

    PubMed  CAS  Google Scholar 

  190. Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS (2007) Long-term aspirin use and mortality in women. Arch Intern Med 167(6):562–572. doi:167/6/562 [pii] 10.1001/archinte.167.6.562

    PubMed  Google Scholar 

  191. Coghill AE, Newcomb PA, Chia VM, Zheng Y, Wernli KJ, Passarelli MN, Potter JD (2011) Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women. Br J Cancer 104(5):763–768. doi:6606041 [pii] 10.1038/sj.bjc.6606041

    PubMed  CAS  Google Scholar 

  192. Zell JA, Ziogas A, Bernstein L, Clarke CA, Deapen D, Largent JA, Neuhausen SL, Stram DO, Ursin G, Anton-Culver H (2009) Nonsteroidal anti-inflammatory drugs: effects on mortality after colorectal cancer diagnosis. Cancer 115(24):5662–5671. doi:10.1002/cncr.24705

    PubMed  Google Scholar 

  193. Din FV, Theodoratou E, Farrington SM, Tenesa A, Barnetson RA, Cetnarskyj R, Stark L, Porteous ME, Campbell H, Dunlop MG (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59(12):1670–1679. doi:gut.2009.203000 [pii] 10.1136/gut.2009.203000

    PubMed  CAS  Google Scholar 

  194. Chan AT, Ogino S, Fuchs CS (2009) Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302(6):649–658. doi:302/6/649 [pii] 10.1001/jama.2009.1112

    PubMed  CAS  Google Scholar 

  195. Bastiaannet E, Sampieri K, Dekkers OM, de Craen AJ, van Herk-Sukel MP, Lemmens V, van den Broek CB, Coebergh JW, Herings RM, van de Velde CJ, Fodde R, Liefers GJ (2012) Use of aspirin postdiagnosis improves survival for colon cancer patients. Br J Cancer 106(9):1564–1570. doi:bjc2012101 [pii] 10.1038/bjc.2012.101

    PubMed  CAS  Google Scholar 

  196. Walker AJ, Grainge MJ, Card TR (2012) Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study. Br J Cancer 107(9):1602–1607. doi:bjc2012427 [pii] 10.1038/bjc.2012.427

    PubMed  CAS  Google Scholar 

  197. Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356(21):2131–2142. doi:356/21/2131 [pii] 10.1056/NEJMoa067208

    PubMed  CAS  Google Scholar 

  198. Benamouzig R, Uzzan B, Martin A, Deyra J, Little J, Girard B, Chaussade S (2010) Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention. Gut 59(5):622–629. doi:59/5/622 [pii] 10.1136/gut.2008.175406

    PubMed  CAS  Google Scholar 

  199. Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (2012) Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 367(17):1596–1606. doi:10.1056/NEJMoa1207756

    PubMed  CAS  Google Scholar 

  200. Johnson CC, Hayes RB, Schoen RE, Gunter MJ, Huang WY (2010) Non-steroidal anti-­inflammatory drug use and colorectal polyps in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Gastroenterol 105(12):2646–2655. doi:ajg2010349 [pii] 10.1038/ajg.2010.349

    PubMed  CAS  Google Scholar 

  201. Zhang X, Smith-Warner SA, Chan AT, Wu K, Spiegelman D, Fuchs CS, Willett WC, Giovannucci EL (2011) Aspirin use, body mass index, physical activity, plasma C-peptide, and colon cancer risk in US health professionals. Am J Epidemiol 174(4):459–467. doi:kwr115 [pii] 10.1093/aje/kwr115

    PubMed  Google Scholar 

  202. Kim S, Baron JA, Mott LA, Burke CA, Church TR, McKeown-Eyssen GE, Cole BF, Haile RW, Sandler RS (2006) Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States). Cancer Causes Control 17(10):1299–1304. doi:10.1007/s10552-006-0075-x

    PubMed  Google Scholar 

  203. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B (2000) The effect of celecoxib, a cyclooxygenase-­2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342(26):1946–1952

    PubMed  CAS  Google Scholar 

  204. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 355(9):885–895. doi:355/9/885 [pii] 10.1056/NEJMoa061652

    PubMed  CAS  Google Scholar 

  205. Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, Bolognese JA, Oxenius B, Horgan K, Loftus S, Morton DG (2006) A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131(6):1674–1682. doi:S0016-­5085(06)01994-9 [pii] 10.1053/j.gastro.2006.08.079

    PubMed  CAS  Google Scholar 

  206. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET (2006) Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 355(9):873–884

    PubMed  CAS  Google Scholar 

  207. Yan M, Myung SJ, Fink SP, Lawrence E, Lutterbaugh J, Yang P, Zhou X, Liu D, Rerko RM, Willis J, Dawson D, Tai HH, Barnholtz-Sloan JS, Newman RA, Bertagnolli MM, Markowitz SD (2009) 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors. Proc Natl Acad Sci U S A 106(23):9409–9413. doi:0902367106 [pii] 10.1073/pnas.0902367106

    PubMed  CAS  Google Scholar 

  208. Tai HH, Chi X, Tong M (2011) Regulation of 15-hydroxyprostaglandin dehydrogenase (15-­PGDH) by non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins Other Lipid Mediat 96(1–4):37–40. doi:S1098-8823(11)00045-1 [pii] 10.1016/j.prostaglandins.2011.06.005

    PubMed  CAS  Google Scholar 

  209. Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL (2008) Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet 372(9651):1756–1764. doi:S0140-6736(08)61490-7 [pii] 10.1016/S0140-6736(08)61490-7

    PubMed  CAS  Google Scholar 

  210. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352(11):1092–1102. doi:NEJMoa050493 [pii] 10.1056/NEJMoa050493

    PubMed  CAS  Google Scholar 

  211. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352(11):1071–1080. doi:NEJMoa050405 [pii] 10.1056/NEJMoa050405

    PubMed  CAS  Google Scholar 

  212. Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B, Eagle C, Hawk E, Lechuga M, Zauber AG, Bertagnolli MM, Arber N, Wittes J (2006) Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 114(10):1028–1035. doi:CIRCULATIONAHA.106.636746 [pii] 10.1161/CIRCULATIONAHA.106.636746

    PubMed  CAS  Google Scholar 

  213. Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, Stokes JC, Julier P, Iveson C, Duvvuri R, McConkey CC (2007) Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 357(4):360–369. doi:357/4/360 [pii] 10.1056/NEJMoa071841

    PubMed  CAS  Google Scholar 

  214. Rostom A, Dube C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D (2007) Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146(5):376–389. doi:146/5/376 [pii]

    PubMed  Google Scholar 

  215. Chan AT, Sima CS, Zauber AG, Ridker PM, Hawk ET, Bertagnolli MM (2011) C-reactive protein and risk of colorectal adenoma according to celecoxib treatment. Cancer Prev Res (Phila) 4(8):1172–1180. doi:4/8/1172 [pii] 10.1158/1940-6207.CAPR-10-0403

    CAS  Google Scholar 

  216. Luo T, Yan HM, He P, Luo Y, Yang YF, Zheng H (2012) Aspirin use and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 131(2):581–587. doi:10.1007/s10549-011-1747-0

    PubMed  CAS  Google Scholar 

  217. Takkouche B, Regueira-Mendez C, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst 100(20):1439–1447. doi:djn324 [pii] 10.1093/jnci/djn324

    PubMed  CAS  Google Scholar 

  218. Ashok V, Dash C, Rohan TE, Sprafka JM, Terry PD (2011) Selective cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast 20(1):66–70. doi:S0960-9776(10)00176-1 [pii] 10.1016/j.breast.2010.07.004

    PubMed  Google Scholar 

  219. Brasky TM, Bonner MR, Moysich KB, Ambrosone CB, Nie J, Tao MH, Edge SB, Kallakury BV, Marian C, Trevisan M, Shields PG, Freudenheim JL (2010) Non-steroidal anti-­inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study. Cancer Causes Control 21(9):1503–1512. doi:10.1007/s10552-010-9579-5

    PubMed  Google Scholar 

  220. Harris RE, Beebe-Donk J, Alshafie GA (2006) Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 6:27. doi:1471-2407-6-27 [pii] 10.1186/1471-2407-6-27

    PubMed  Google Scholar 

  221. Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, Loar A, Rodabough RJ, White E, McTiernan A (2003) Breast cancer and nonsteroidal ­anti-­inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63(18):6096–6101

    PubMed  CAS  Google Scholar 

  222. Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291(20):2433–2440

    PubMed  CAS  Google Scholar 

  223. Bosco JL, Palmer JR, Boggs DA, Hatch EE, Rosenberg L (2011) Regular aspirin use and breast cancer risk in US Black women. Cancer Causes Control 22(11):1553–1561. doi:10.1007/s10552-011-9832-6

    PubMed  Google Scholar 

  224. Garcia Rodriguez LA, Gonzalez-Perez A (2004) Risk of breast cancer among users of aspirin and other anti-inflammatory drugs. Br J Cancer 91(3):525–529. doi:10.1038/sj.bjc.6602003 6602003 [pii]

    PubMed  CAS  Google Scholar 

  225. Rahme E, Ghosn J, Dasgupta K, Rajan R, Hudson M (2005) Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer 5:159. doi:1471-­2407-5-159 [pii] 10.1186/1471-2407-5-159

    PubMed  Google Scholar 

  226. Vinogradova Y, Coupland C, Hippisley-Cox J (2011) Exposure to cyclooxygenase-2 inhibitors and risk of cancer: nested case–control studies. Br J Cancer 105(3):452–459. doi:bjc2011252 [pii] 10.1038/bjc.2011.252

    PubMed  CAS  Google Scholar 

  227. Valsecchi ME, Pomerantz SC, Jaslow R, Tester W (2009) Reduced risk of bone metastasis for patients with breast cancer who use COX-2 inhibitors. Clin Breast Cancer 9(4):225–230. doi:S1526-8209(11)70672-3 [pii] 10.3816/CBC.2009.n.038

    PubMed  CAS  Google Scholar 

  228. Brasky TM, Bonner MR, Moysich KB, Ambrosone CB, Nie J, Tao MH, Edge SB, Kallakury BV, Marian C, Goerlitz DS, Trevisan M, Shields PG, Freudenheim JL (2011) Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype. Cancer Causes Control 22(7):965–975. doi:10.1007/s10552-011-9769-9

    PubMed  Google Scholar 

  229. Friis S, Thomassen L, Sorensen HT, Tjonneland A, Overvad K, Cronin-Fenton DP, Vogel U, McLaughlin JK, Blot WJ, Olsen JH (2008) Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study. Eur J Cancer Prev 17(2):88–96. doi:10.1097/CEJ.0b013e3282b6fd55 00008469-200804000-00004 [pii]

    PubMed  Google Scholar 

  230. Ready A, Velicer CM, McTiernan A, White E (2008) NSAID use and breast cancer risk in the VITAL cohort. Breast Cancer Res Treat 109(3):533–543. doi:10.1007/s10549-007-9665-x

    PubMed  CAS  Google Scholar 

  231. Cronin-Fenton DP, Pedersen L, Lash TL, Friis S, Baron JA, Sorensen HT (2010) Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case–control study. Breast Cancer Res 12(2):R15. doi:bcr2482 [pii] 10.1186/bcr2482

    PubMed  Google Scholar 

  232. Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA (1996) Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 88(14):988–993

    PubMed  CAS  Google Scholar 

  233. Eliassen AH, Chen WY, Spiegelman D, Willett WC, Hunter DJ, Hankinson SE (2009) Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and risk of breast cancer among premenopausal women in the Nurses' Health Study II. Arch Intern Med 169(2):115–121; discussion 121. doi:169/2/115 [pii] 10.1001/archinternmed.2008.537

    Google Scholar 

  234. Zhang X, Smith-Warner SA, Collins LC, Rosner B, Willett WC, Hankinson SE (2012) Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol 30(28):3468–3477. doi:JCO.2012.42.2006 [pii] 10.1200/JCO.2012.42.2006

    PubMed  CAS  Google Scholar 

  235. Jacobs EJ, Thun MJ, Connell CJ, Rodriguez C, Henley SJ, Feigelson HS, Patel AV, Flanders WD, Calle EE (2005) Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev 14(1):261–264

    PubMed  CAS  Google Scholar 

  236. Gierach GL, Lacey JV Jr, Schatzkin A, Leitzmann MF, Richesson D, Hollenbeck AR, Brinton LA (2008) Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Res 10(2):R38

    PubMed  Google Scholar 

  237. Marshall SF, Bernstein L, Anton-Culver H, Deapen D, Horn-Ross PL, Mohrenweiser H, Peel D, Pinder R, Purdie DM, Reynolds P, Stram D, West D, Wright WE, Ziogas A, Ross RK (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97(11):805–812

    PubMed  CAS  Google Scholar 

  238. Gill JK, Maskarinec G, Wilkens LR, Pike MC, Henderson BE, Kolonel LN (2007) Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort. Am J Epidemiol 166(10):1150–1158. doi:kwm195 [pii] 10.1093/aje/kwm195

    PubMed  Google Scholar 

  239. Zhang Y, Coogan PF, Palmer JR, Strom BL, Rosenberg L (2005) Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case–Control Surveillance Study revisited. Am J Epidemiol 162(2):165–170. doi:kwi182 [pii] 10.1093/aje/kwi182

    PubMed  Google Scholar 

  240. Gallicchio L, Visvanathan K, Burke A, Hoffman SC, Helzlsouer KJ (2007) Nonsteroidal anti-­inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD. Int J Cancer 121(1):211–215. doi:10.1002/ijc.22656

    PubMed  CAS  Google Scholar 

  241. Kirsh VA, Kreiger N, Cotterchio M, Sloan M, Theis B (2007) Nonsteroidal antiinflammatory drug use and breast cancer risk: subgroup findings. Am J Epidemiol 166(6):709–716. doi:kwm216 [pii] 10.1093/aje/kwm216

    PubMed  Google Scholar 

  242. Bardia A, Olson JE, Vachon CM, Lazovich D, Vierkant RA, Wang AH, Limburg PJ, Anderson KE, Cerhan JR (2011) Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study. Breast Cancer Res Treat 126(1):149–155. doi:10.1007/s10549-010-1074-x

    PubMed  CAS  Google Scholar 

  243. Blair CK, Sweeney C, Anderson KE, Folsom AR (2007) NSAID use and survival after breast cancer diagnosis in post-menopausal women. Breast Cancer Res Treat 101(2):191–197. doi:10.1007/s10549-006-9277-x

    PubMed  CAS  Google Scholar 

  244. Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28(9):1467–1472. doi:JCO.2009.22.7918 [pii] 10.1200/JCO.2009.22.7918

    PubMed  CAS  Google Scholar 

  245. Kwan ML, Habel LA, Slattery ML, Caan B (2007) NSAIDs and breast cancer recurrence in a prospective cohort study. Cancer Causes Control 18(6):613–620. doi:10.1007/s10552-007-9003-y

    PubMed  Google Scholar 

  246. Li Y, Brasky TM, Nie J, Ambrosone CB, McCann SE, Shields PG, Trevisan M, Edge SB, Freudenheim JL (2012) Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev 21(1):239–242. doi:1055–9965.EPI-11-1012 [pii] 10.1158/1055-9965.EPI-11-1012

    PubMed  CAS  Google Scholar 

  247. Wernli KJ, Hampton JM, Trentham-Dietz A, Newcomb PA (2011) Use of antidepressants and NSAIDs in relation to mortality in long-term breast cancer survivors. Pharmacoepidemiol Drug Saf 20(2):131–137. doi:10.1002/pds.2064

    PubMed  Google Scholar 

  248. Canney PA, Machin MA, Curto J (2006) A feasibility study of the efficacy and tolerability of the combination of Exemestane with the COX-2 inhibitor Celecoxib in post-menopausal patients with advanced breast cancer. Eur J Cancer 42(16):2751–2756. doi:S0959-­8049(06)00723-4 [pii] 10.1016/j.ejca.2006.08.014

    PubMed  CAS  Google Scholar 

  249. Dang CT, Dannenberg AJ, Subbaramaiah K, Dickler MN, Moasser MM, Seidman AD, D’Andrea GM, Theodoulou M, Panageas KS, Norton L, Hudis CA (2004) Phase II study of celecoxib and trastuzumab in metastatic breast cancer patients who have progressed after prior trastuzumab-based treatments. Clin Cancer Res 10(12 pt 1):4062–4067. doi:10.1158/1078-0432.CCR-03-0463 10/12/4062 [pii]

    PubMed  CAS  Google Scholar 

  250. Dirix LY, Ignacio J, Nag S, Bapsy P, Gomez H, Raghunadharao D, Paridaens R, Jones S, Falcon S, Carpentieri M, Abbattista A, Lobelle JP (2008) Treatment of advanced hormone-­sensitive breast cancer in postmenopausal women with exemestane alone or in combination with celecoxib. J Clin Oncol 26(8):1253–1259. doi:26/8/1253 [pii] 10.1200/JCO.2007.13.3744

    PubMed  CAS  Google Scholar 

  251. Fabi A, Metro G, Papaldo P, Mottolese M, Melucci E, Carlini P, Sperduti I, Russillo M, Gelibter A, Ferretti G, Tomao S, Milella M, Cognetti F (2008) Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation. Cancer Chemother Pharmacol 62(4):717–725. doi:10.1007/s00280-007-0650-1

    PubMed  CAS  Google Scholar 

  252. Chow LW, Yip AY, Loo WT, Lam CK, Toi M (2008) Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer. J Steroid Biochem Mol Biol 111(1–2):13–17. doi:S0960-0760(08)00089-7 [pii] 10.1016/j.jsbmb.2008.04.004

    PubMed  CAS  Google Scholar 

  253. Sauter ER, Qin W, Schlatter L, Hewett JE, Flynn JT (2006) Celecoxib decreases prostaglandin E2 concentrations in nipple aspirate fluid from high risk postmenopausal women and women with breast cancer. BMC Cancer 6:248. doi:1471-2407-6-248 [pii] 10.1186/1471-2407-6-248

    PubMed  Google Scholar 

  254. Bundred NJ, Cramer A, Morris J, Renshaw L, Cheung KL, Flint P, Johnson R, Young O, Landberg G, Grassby S, Turner L, Baildam A, Barr L, Dixon JM (2010) Cyclooxygenase-2 inhibition does not improve the reduction in ductal carcinoma in situ proliferation with aromatase inhibitor therapy: results of the ERISAC randomized placebo-controlled trial. Clin Cancer Res 16(5):1605–1612. doi:1078–0432.CCR-09-1623 [pii] 10.1158/1078-0432.CCR-09-1623

    PubMed  CAS  Google Scholar 

  255. Martin LA, Davies GL, Weigel MT, Betambeau N, Hills MJ, Salter J, Walsh G, A’Hern R, Dowsett M (2010) Pre-surgical study of the biological effects of the selective cyclo-­oxygenase-2 inhibitor celecoxib in patients with primary breast cancer. Breast Cancer Res Treat 123(3):829–836. doi:10.1007/s10549-010-1100-z

    PubMed  Google Scholar 

  256. Lustberg MB, Povoski SP, Zhao W, Ziegler RM, Sugimoto Y, Ruppert AS, Lehman AM, Shiels DR, Mrozek E, Ramaswamy B, Layman RM, Brueggemeier RW, Shapiro CL (2011) Phase II trial of neoadjuvant exemestane in combination with celecoxib in postmenopausal women who have breast cancer. Clin Breast Cancer 11(4):221–227. doi:S1526-­8209(11)00035-8 [pii] 10.1016/j.clbc.2011.03.022

    PubMed  CAS  Google Scholar 

  257. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545. doi:S0140-6736(00)04046-0 [pii] 10.1016/S0140-6736(00)04046-0

    PubMed  CAS  Google Scholar 

  258. Harvey AE, Lashinger LM, Hursting SD (2011) The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45–52. doi:10.1111/j.1749-6632.2011.06096.x

    PubMed  CAS  Google Scholar 

  259. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8(12):915–928. doi:nrc2536 [pii] 10.1038/nrc2536

    PubMed  CAS  Google Scholar 

  260. Wong KK, Engelman JA, Cantley LC (2010) Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev 20(1):87–90. doi:S0959-437X(09)00178-6 [pii] 10.1016/j.gde.2009.11.002

    PubMed  CAS  Google Scholar 

  261. Desbois-Mouthon C, Cadoret A, Blivet-Van Eggelpoel MJ, Bertrand F, Cherqui G, Perret C, Capeau J (2001) Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation. Oncogene 20(2):252–259. doi:10.1038/sj.onc.1204064

    PubMed  CAS  Google Scholar 

  262. Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653(1):1–24

    PubMed  CAS  Google Scholar 

  263. Cleary MP, Grossmann ME, Ray A (2010) Effect of obesity on breast cancer development. Vet Pathol 47(2):202–213. doi:0300985809357753 [pii] 10.1177/0300985809357753

    PubMed  CAS  Google Scholar 

  264. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11(2):191–198. doi:nm1185 [pii] 10.1038/nm1185

    PubMed  CAS  Google Scholar 

  265. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11(2):183–190. doi:nm1166 [pii] 10.1038/nm1166

    PubMed  CAS  Google Scholar 

  266. Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J, White NM, Ma JT, Zhou J, Qi N, Westcott D, Delproposto JB, Blackwell TS, Yull FE, Saltiel AR (2009) The protein kinase IKKepsilon regulates energy balance in obese mice. Cell 138(5):961–975. doi:S0092-­8674(09)00793-4 [pii] 10.1016/j.cell.2009.06.046

    PubMed  CAS  Google Scholar 

  267. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293(5535):1673–1677. doi:10.1126/science.1061620 293/5535/1673 [pii]

    PubMed  CAS  Google Scholar 

  268. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. doi:S0092-8674(12)00351-0 [pii] 10.1016/j.cell.2012.03.017

    PubMed  CAS  Google Scholar 

  269. Piazza GA, Alberts DS, Hixson LJ, Paranka NS, Li H, Finn T, Bogert C, Guillen JM, Brendel K, Gross PH, Sperl G, Ritchie J, Burt RW, Ellsworth L, Ahnen DJ, Pamukcu R (1997) Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res 57(14):2909–2915

    PubMed  CAS  Google Scholar 

  270. Elder DJ, Halton DE, Hague A, Paraskeva C (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(10):1679–1683

    PubMed  CAS  Google Scholar 

  271. Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI, Rigas B (1996) Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem Pharmacol 52(2):237–245

    PubMed  CAS  Google Scholar 

  272. Zhang X, Morham SG, Langenbach R, Young DA (1999) Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med 190(4):451–459

    PubMed  CAS  Google Scholar 

  273. Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58(2):362–366

    PubMed  CAS  Google Scholar 

  274. Chan TA, Morin PJ, Vogelstein B, Kinzler KW (1998) Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis. Proc Natl Acad Sci U S A 95(2):681–686

    PubMed  CAS  Google Scholar 

  275. Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM (2000) Intracellular unesterified arachidonic acid signals apoptosis. Proc Natl Acad Sci U S A 97(21):11280–11285

    PubMed  CAS  Google Scholar 

  276. Gupta RA, Tan J, Krause WF, Geraci MW, Willson TM, Dey SK, DuBois RN (2000) Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Proc Natl Acad Sci U S A 97(24):13275–13280. doi:10.1073/pnas.97.24.13275 97/24/13275 [pii]

    PubMed  CAS  Google Scholar 

  277. Cutler NS, Graves-Deal R, LaFleur BJ, Gao Z, Boman BM, Whitehead RH, Terry E, Morrow JD, Coffey RJ (2003) Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells. Cancer Res 63(8):1748–1751

    PubMed  CAS  Google Scholar 

  278. Piazza GA, Rahm AL, Krutzsch M, Sperl G, Paranka NS, Gross PH, Brendel K, Burt RW, Alberts DS, Pamukcu R, Ahnen DJ (1995) Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 55(14):3110–3116

    PubMed  CAS  Google Scholar 

  279. Shureiqi I, Chen D, Lee JJ, Yang P, Newman RA, Brenner DE, Lotan R, Fischer SM, Lippman SM (2000) 15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-­induced apoptosis in colorectal cancer cells. J Natl Cancer Inst 92(14):1136–1142

    PubMed  CAS  Google Scholar 

  280. Wu J, Xia HH, Tu SP, Fan DM, Lin MC, Kung HF, Lam SK, Wong BC (2003) 15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer. Carcinogenesis 24(2):243–247

    PubMed  CAS  Google Scholar 

  281. Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE (2001) Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol 59(4):901–908

    PubMed  CAS  Google Scholar 

  282. Zhang Z, DuBois RN (2000) Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. Gastroenterology 118(6):1012–1017. doi:S0016508500948704 [pii]

    PubMed  CAS  Google Scholar 

  283. He TC, Chan TA, Vogelstein B, Kinzler KW (1999) PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99(3):335–345. doi:S0092-8674(00)81664-5 [pii]

    PubMed  CAS  Google Scholar 

  284. Arico S, Pattingre S, Bauvy C, Gane P, Barbat A, Codogno P, Ogier-Denis E (2002) Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 277(31):27613–27621. doi:10.1074/jbc.M201119200 M201119200 [pii]

    PubMed  CAS  Google Scholar 

  285. Liou JY, Ghelani D, Yeh S, Wu KK (2007) Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. Cancer Res 67(7):3185–3191. doi:67/7/3185 [pii] 10.1158/0008-5472.CAN-06-3431

    PubMed  CAS  Google Scholar 

  286. Ouyang N, Williams JL, Rigas B (2006) NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)delta expression in APC(min/+) mice proportionally to their tumor inhibitory effect: implications for the role of PPARdelta in carcinogenesis. Carcinogenesis 27(2):232–239. doi:bgi221 [pii] 10.1093/carcin/bgi221

    PubMed  CAS  Google Scholar 

  287. Shureiqi I, Jiang W, Zuo X, Wu Y, Stimmel JB, Leesnitzer LM, Morris JS, Fan HZ, Fischer SM, Lippman SM (2003) The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells. Proc Natl Acad Sci U S A 100(17):9968–9973. doi:10.1073/pnas.1631086100 1631086100 [pii]

    PubMed  CAS  Google Scholar 

  288. Qiu W, Wang X, Leibowitz B, Liu H, Barker N, Okada H, Oue N, Yasui W, Clevers H, Schoen RE, Yu J, Zhang L (2010) Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci U S A 107(46):20027–20032. doi:1010430107 [pii] 10.1073/pnas.1010430107

    PubMed  CAS  Google Scholar 

  289. Liou JY, Ellent DP, Lee S, Goldsby J, Ko BS, Matijevic N, Huang JC, Wu KK (2007) Cyclooxygenase-2-derived prostaglandin e2 protects mouse embryonic stem cells from apoptosis. Stem Cells 25(5):1096–1103. doi:2006–0505 [pii] 10.1634/stemcells.2006-0505

    PubMed  CAS  Google Scholar 

  290. Boon EM, Keller JJ, Wormhoudt TA, Giardiello FM, Offerhaus GJ, van der Neut R, Pals ST (2004) Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. Br J Cancer 90(1):224–229. doi:10.1038/sj.bjc.6601505 6601505 [pii]

    PubMed  CAS  Google Scholar 

  291. Bos CL, Kodach LL, van den Brink GR, Diks SH, van Santen MM, Richel DJ, Peppelenbosch MP, Hardwick JC (2006) Effect of aspirin on the Wnt/beta-catenin pathway is mediated via protein phosphatase 2A. Oncogene 25(49):6447–6456. doi:1209658 [pii] 10.1038/sj.onc.1209658

    PubMed  CAS  Google Scholar 

  292. Dihlmann S, Siermann A, von Knebel Doeberitz M (2001) The nonsteroidal anti-­inflammatory drugs aspirin and indomethacin attenuate beta-catenin/TCF-4 signaling. Oncogene 20(5):645–653. doi:10.1038/sj.onc.1204123

    PubMed  CAS  Google Scholar 

  293. Greenspan EJ, Madigan JP, Boardman LA, Rosenberg DW (2011) Ibuprofen inhibits activation of nuclear {beta}-catenin in human colon adenomas and induces the phosphorylation of GSK-3{beta}. Cancer Prev Res (Phila) 4(1):161–171. doi:4/1/161 [pii] 10.1158/1940-6207.CAPR-10-0021

    CAS  Google Scholar 

  294. Shao J, Jung C, Liu C, Sheng H (2005) Prostaglandin E2 stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. J Biol Chem 280(28):26565–26572. doi:M413056200 [pii] 10.1074/jbc.M413056200

    PubMed  CAS  Google Scholar 

  295. Thompson WJ, Piazza GA, Li H, Liu L, Fetter J, Zhu B, Sperl G, Ahnen D, Pamukcu R (2000) Exisulind induction of apoptosis involves guanosine 3′,5′-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res 60(13):3338–3342

    PubMed  CAS  Google Scholar 

  296. Tinsley HN, Gary BD, Keeton AB, Zhang W, Abadi AH, Reynolds RC, Piazza GA (2009) Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G. Mol Cancer Ther 8(12):3331–3340. doi:1535–7163.MCT-09-0758 [pii] 10.1158/1535-7163.MCT-09-0758

    PubMed  CAS  Google Scholar 

  297. Tinsley HN, Gary BD, Thaiparambil J, Li N, Lu W, Li Y, Maxuitenko YY, Keeton AB, Piazza GA (2010) Colon tumor cell growth-inhibitory activity of sulindac sulfide and other nonsteroidal anti-inflammatory drugs is associated with phosphodiesterase 5 inhibition. Cancer Prev Res (Phila) 3(10):1303–1313. doi:1940–6207.CAPR-10-0030 [pii] 10.1158/1940-6207.CAPR-10-0030

    CAS  Google Scholar 

  298. Harris RM, Hawker RJ, Langman MJ, Singh S, Waring RH (1998) Inhibition of phenolsulphotransferase by salicylic acid: a possible mechanism by which aspirin may reduce carcinogenesis. Gut 42(2):272–275

    PubMed  CAS  Google Scholar 

  299. Kopp E, Ghosh S (1994) Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265(5174):956–959

    PubMed  CAS  Google Scholar 

  300. Grilli M, Pizzi M, Memo M, Spano P (1996) Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science 274(5291):1383–1385

    PubMed  CAS  Google Scholar 

  301. Yamamoto Y, Yin MJ, Lin KM, Gaynor RB (1999) Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274(38):27307–27314

    PubMed  CAS  Google Scholar 

  302. Yin MJ, Yamamoto Y, Gaynor RB (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396(6706):77–80. doi:10.1038/23948

    PubMed  CAS  Google Scholar 

  303. Din FV, Stark LA, Dunlop MG (2005) Aspirin-induced nuclear translocation of NFkappaB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency. Br J Cancer 92(6):1137–1143. doi:6602455 [pii] 10.1038/sj.bjc.6602455

    PubMed  CAS  Google Scholar 

  304. Loveridge CJ, MacDonald AD, Thoms HC, Dunlop MG, Stark LA (2008) The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB. Oncogene 27(18):2648–2655. doi:1210891 [pii] 10.1038/sj.onc.1210891

    PubMed  CAS  Google Scholar 

  305. Hsieh PS, Jin JS, Chiang CF, Chan PC, Chen CH, Shih KC (2009) COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity (Silver Spring) 17(6):1150–1157. doi:oby2008674 [pii] 10.1038/oby.2008.674

    CAS  Google Scholar 

  306. Gonzalez-Ortiz M, Martinez-Abundis E, Balcazar-Munoz BR, Robles-Cervantes JA (2001) Inhibition of cyclooxygenase-1 or -2 on insulin sensitivity in healthy subjects. Horm Metab Res 33(4):250–253

    PubMed  CAS  Google Scholar 

  307. Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI (2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 109(10):1321–1326. doi:10.1172/JCI14955

    PubMed  CAS  Google Scholar 

  308. Fleischman A, Shoelson SE, Bernier R, Goldfine AB (2008) Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31(2):289–294. doi:dc07-1338 [pii] 10.2337/dc07-1338

    PubMed  CAS  Google Scholar 

  309. Shoelson SE, Lee J, Yuan M (2003) Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27(suppl 3):S49–S52. doi:10.1038/sj.ijo.0802501 0802501 [pii]

    PubMed  CAS  Google Scholar 

  310. Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE (2008) Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci 1(1):36–43. doi:10.1111/j.1752-8062.2008.00026.x

    PubMed  CAS  Google Scholar 

  311. Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG (2012) The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336(6083):918–922. doi:science.1215327 [pii] 10.1126/science.1215327

    PubMed  CAS  Google Scholar 

  312. Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG (2012) Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology 142(7):1504–1515 e1503. doi:S0016-5085(12)00313-7 [pii] 10.1053/j.gastro.2012.02.05

    Google Scholar 

  313. Brunelli C, Amici C, Angelini M, Fracassi C, Belardo G, Santoro MG (2012) The non-­steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells. Biochem J 443(2):379–386. doi:BJ20111236 [pii] 10.1042/BJ20111236

    PubMed  CAS  Google Scholar 

  314. Marimuthu S, Chivukula RS, Alfonso LF, Moridani M, Hagen FK, Bhat GJ (2011) Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: identification of novel targets. Int J Oncol 39(5):1273–1283. doi:10.3892/ijo.2011.1113

    PubMed  CAS  Google Scholar 

  315. Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 92(21):9475–9479

    PubMed  CAS  Google Scholar 

  316. Ruschoff J, Wallinger S, Dietmaier W, Bocker T, Brockhoff G, Hofstadter F, Fishel R (1998) Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Proc Natl Acad Sci U S A 95(19):11301–11306

    PubMed  CAS  Google Scholar 

  317. He H, Xia HH, Wang JD, Gu Q, Lin MC, Zou B, Lam SK, Chan AO, Yuen MF, Kung HF, Wong BC (2006) Inhibition of human telomerase reverse transcriptase by nonsteroidal ­antiinflammatory drugs in colon carcinoma. Cancer 106(6):1243–1249. doi: 10.1002/cncr.21694

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA

    Louise R. Howe Ph.D.

Authors
  1. Louise R. Howe Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Louise R. Howe Ph.D. .

Editor information

Editors and Affiliations

  1. , Department of Medicine, Weill Cornell Medical College, 525 E. 68th St. Room F-206, New York, 10065, New York, USA

    Andrew J. Dannenberg

  2. School of Medicine, Center for Science, Health & Society, Case Western Reserve University, Euclid Ave. 10900, Cleveland, 44106, Ohio, USA

    Nathan A. Berger

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Howe, L.R. (2013). Pharmacologic Interventions with NSAIDs. In: Dannenberg, A., Berger, N. (eds) Obesity, Inflammation and Cancer. Energy Balance and Cancer, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6819-6_11

Download citation

Publish with us

Policies and ethics

Search

Navigation