European Journal of Cancer
Volume 41, Issue 13 , Pages 1889-1910 , September 2005

The chemopreventive agent development research program in the Division of Cancer Prevention of the US National Cancer Institute: An overview

Received 25 April 2005 ,Accepted 25 April 2005.

References 

  1. Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res. 1976;36(7 PT 2):2699–2702
  2. Wattenberg LW. Chemoprevention of cancer. Cancer Res. 1985;45(1):1–8
  3. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer, report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–1388
  4. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342(26):1946–1952
  5. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215–224
  6. Vogel VG. Follow-up of the breast cancer prevention trial and the future of breast cancer prevention efforts. Clin Cancer Res. 2001;7(12 Suppl.):4413s–4418sdiscussion 4411s–4412s
  7. Klein EA, Thompson IM, Lippman SM, et al. SELECT, the selenium and vitamin E cancer prevention trial. Urol Oncol. 2003;21(1):59–65
  8. Reddy BS, Nayini J, Tokumo K, et al. Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with d,l-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. Cancer Res. 1990;50(9):2562–2568
  9. Jacoby RF, Seibert K, Cole CE, et al. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the Min mouse model of adenomatous polyposis. Cancer Res. 2000;60(18):5040–5044
  10. Reddy BS, Hirose Y, Lubet R, et al. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res. 2000;60(2):293–297
  11. Grubbs CJ, Lubet RA, Koki AT, et al. Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res. 2000;60(20):5599–5602
  12. Fischer SM, Lo HH, Gordon GB, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog. 1999;25(4):231–240
  13. Solomon SD, McMurray JV, Pfeffer MA, et al. Cardiovascular risk associated with celebrex in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352(11):1080–1091
  14. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352(11):1092–1102
  15. Zhu J, Song X, Lin HP, et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J Natl Cancer Inst. 2002;94(23):1745–1757
  16. Shureiqi I, Lippman SM. Lipoxygenase modulation to reverse carcinogenesis. Cancer Res. 2001;61(17):6307–6312
  17. Charlier C, Michaux C. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003;38(7–8):645–659
  18. Shureiqi I, Chen D, Lee JJ, et al. 15-LOX-1, a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells. J Natl Cancer Inst. 2000;92(14):1136–1142
  19. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther. 1999;83(3):217–244
  20. Chiang N, Bermudez EA, Ridker PM, et al. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci USA. 2004;101(42):15178–15183
  21. Rigas B, Kashfi K. Nitric-oxide-donating NSAIDs as agents for cancer prevention. Trends Mol Med. 2004;10(7):324–330
  22. Ridnour LA, Thomas DD, Mancardi D, et al. The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. Biol Chem. 2004;385(1):1–10
  23. Crowell JA, Steele VE, Sigman CC, et al. Is inducible nitric oxide synthase a target for chemoprevention?. Mol Cancer Ther. 2003;2(8):815–823
  24. Bak AW, McKnight W, Li P, et al. Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma. Life Sci. 1998;62(23):PL367–PL373
  25. Kashfi K, Ryan Y, Qiao LL, et al. Nitric oxide-donating nonsteroidal anti-inflammatory drugs inhibit the growth of various cultured human cancer cells, evidence of a tissue type-independent effect. J Pharmacol Exp Ther. 2002;303(3):1273–1282
  26. Kaza CS, Kashfi K, Rigas B. Colon cancer prevention with NO-releasing NSAIDs. Prostaglandins Other Lipid Mediat. 2002;67(2):107–120
  27. Moskowitz DW, Johnson FE. The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. Curr Top Med Chem. 2004;4(13):1433–1454
  28. Berry C, Touyz R, Dominiczak AF, et al. Angiotensin receptors, signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol Heart Circ Physiol. 2001;281(6):H2337–H2365
  29. Lever AF, Hole DJ, Gillis CR, et al. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?. Lancet. 1998;352(9123):179–184
  30. Plummer SM, Holloway KA, Manson MM, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene. 1999;18(44):6013–6020
  31. St-Germain ME, Gagnon V, Parent S, et al. Regulation of COX-2 protein expression by Akt in endometrial cancer cells is mediated through NF-kappaB/IkappaB pathway. Mol Cancer. 2004;3(1):7
  32. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2(7):489–501
  33. Bellacosa A, Testa JR, Moore R, et al. A portrait of AKT kinases, human cancer and animal models depict a family with strong individualities. Cancer Biol Ther. 2004;3(3):268–275
  34. Mitsiades CS, Mitsiades N, Koutsilieris M. The Akt pathway, molecular targets for anti-cancer drug development. Curr Cancer Drug Targets. 2004;4(3):235–256
  35. Lu Y, Wang H, Mills GB. Targeting PI3K-AKT pathway for cancer therapy. Rev Clin Exp Hematol. 2003;7(2):205–228
  36. Paez J, Sellers WR. PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res. 2003;115:145–167
  37. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554
  38. West KA, Brognard J, Clark AS, et al. Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest. 2003;111(1):81–90
  39. West KA, Linnoila IR, Belinsky SA, et al. Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3′-kinase/Akt pathway in vitro and in vivo. Cancer Res. 2004;64(2):446–451
  40. Castillo SS, Brognard J, Petukhov PA, et al. Preferential inhibition of Akt and killing of Akt-dependent cancer cells by rationally designed phosphatidylinositol ether lipid analogues. Cancer Res. 2004;64(8):2782–2792
  41. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin, a component of tumeric (Curcuma longa). J Altern Complement Med. 2003;9(1):161–168
  42. Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des. 2002;8(19):1695–1706
  43. Leu TH, Maa MC. The molecular mechanisms for the antitumourigenic effect of curcumin. Curr Med Chem Anti-Canc Agents. 2002;2(3):357–370
  44. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin, preclinical and clinical studies. Anticancer Res. 2003;23(1A):363–398
  45. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7(7):1894–1900
  46. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895–2900
  47. Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005;14(1):120–125
  48. Jong L, Chao WR, Amin K, et al. SR13668, a novel indole derived inhibitor of phospho-Akt potently suppresses tumour growth in various murine xenograft models. Proc Am Assoc Cancer Res. 2004;45:abst. no. 3684
  49. Udeani GO, Zhao GM, Shin YG, et al. Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats. Cancer Chemother Pharmacol. 2001;47(3):263–268
  50. Chun KH, Kosmeder JW, Sun S, et al. Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J Natl Cancer Inst. 2003;95(4):291–302
  51. Lee HY, Suh YA, Kosmeder JW, et al. Deguelin-induced inhibition of cyclooxygenase-2 expression in human bronchial epithelial cells. Clin Cancer Res. 2004;10(3):1074–1079
  52. Murillo G, Kosmeder JW, Pezzuto JM, et al. Deguelin suppresses the formation of carcinogen-induced aberrant crypt foci in the colon of CF-1 mice. Int J Cancer. 2003;104(1):7–11
  53. Udeani GO, Gerhauser C, Thomas CF, et al. Cancer chemopreventive activity mediated by deguelin, a naturally occurring rotenoid. Cancer Res. 1997;57(16):3424–3428
  54. Ito C, Itoigawa M, Kojima N, et al. Cancer chemopreventive activity of rotenoids from Derris trifoliata. Planta Med. 2004;70(1):8–11
  55. Fang N, Casida JE. Anticancer action of cube insecticide, correlation for rotenoid constituents between inhibition of NADH,ubiquinone oxidoreductase and induced ornithine decarboxylase activities. Proc Natl Acad Sci USA. 1998;95(7):3380–3384
  56. Lorberg A, Hall MN. TOR, the first 10 years. Curr Top Microbiol Immunol. 2004;279:1–18
  57. Shamji AF, Nghiem P, Schreiber SL. Integration of growth factor and nutrient signaling, implications for cancer biology. Mol Cell. 2003;12(2):271–280
  58. Martin KA, Blenis J. Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv Cancer Res. 2002;86:1–39
  59. Hidalgo M, Rowinsky EK. The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 2000;19(56):6680–6686
  60. Fingar DC, Richardson CJ, Tee AR, et al. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol. 2004;24(1):200–216
  61. Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15(7):807–826
  62. Gingras AC, Raught B, Sonenberg N. mTOR signaling to translation. Curr Top Microbiol Immunol. 2004;279:169–197
  63. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003;3(4):371–377
  64. Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;349(4):366–381
  65. Shayesteh L, Lu Y, Kuo WL, et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet. 1999;21(1):99–102
  66. Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA. 2002;99(21):13571–13576
  67. Inoki K, Li Y, Zhu T, et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4(9):648–657
  68. Manning BD, Tee AR, Logsdon MN, et al. Identification of the tuberous sclerosis complex-2 tumour suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/Akt pathway. Mol Cell. 2002;10(1):151–162
  69. Louro ID, McKie-Bell P, Gosnell H, et al. The zinc finger protein GLI induces cellular sensitivity to the mTOR inhibitor rapamycin. Cell Growth Differ. 1999;10(7):503–516
  70. Bushman JL. Green tea and cancer in humans, a review of the literature. Nutr Cancer. 1998;31(3):151–159
  71. Higdon JV, Frei B. Tea catechins and polyphenols, health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr. 2003;43(1):89–143
  72. Yang CS, Yang GY, Chung JY, et al. Tea and tea polyphenols in cancer prevention. Adv Exp Med Biol. 2001;492:39–53
  73. Yang CS, Maliakal P, Meng X. Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol. 2002;42:25–54
  74. Shimizu M, Deguchi I, Lim JT, et al. (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin Cancer Res. 2005;11(7):2735–2746
  75. Chow HH, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res. 2003;9(9):3312–3319
  76. Chow HH-S, Hakim IA, Vining DR, et al. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Cancer Epidemiol Biomarkers Prev. 2005;11(12):4627–4633
  77. Masuda M, Suzui M, Lim JT, et al. Epigallocatechin-3-gallate inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clin Cancer Res. 2003;9(9):3486–3491
  78. Cook LS, Goldoft M, Schwartz SM, et al. Incidence of adenocarcinoma of the prostate in Asian immigrants to the United States and their descendants. J Urol. 1999;161(1):152–155
  79. Dai Q, Franke AA, Jin F, et al. Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiol Biomarkers Prev. 2002;11(9):815–821
  80. Wu AH, Wan P, Hankin J, et al. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. 2002;23(9):1491–1496
  81. Adlercreutz H, Honjo H, Higashi A, et al. Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr. 1991;54(6):1093–1100
  82. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342(8881):1209–1210
  83. Casanova M, You L, Gaido KW, et al. Developmental effects of dietary phytoestrogens in Sprague–Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro. Toxicol Sci. 1999;51(2):236–244
  84. Gescher A, Pastorino U, Plummer SM, et al. Suppression of tumour development by substances derived from the diet-mechanisms and clinical implications. Br J Clin Pharmacol. 1998;45(1):1–12
  85. Nevala R, Lassila M, Finckenberg P, et al. Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats. Eur J Pharmacol. 2002;452(1):87–96
  86. Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA. 1993;90(7):2690–2694
  87. Shao ZM, Alpaugh ML, Fontana JA, et al. Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by P21WAF1/CIP1 induction, G2/M arrest, and apoptosis. J Cell Biochem. 1998;69(1):44–54
  88. Yoon HS, Moon SC, Kim ND, et al. Genistein induces apoptosis of RPE-J cells by opening mitochondrial PTP. Biochem Biophys Res Commun. 2000;276(1):151–156
  89. Constantinou AI, Krygier AE, Mehta RR. Genistein induces maturation of cultured human breast cancer cells and prevents tumour growth in nude mice. Am J Clin Nutr. 1998;68(6 Suppl.):1426S–1430S
  90. Pollard M, Luckert PH. Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats. Nutr Cancer. 1997;28(1):41–45
  91. Kato K, Takahashi S, Cui L, et al. Suppressive effects of dietary genistin and daidzin on rat prostate carcinogenesis. Jpn J Cancer Res. 2000;91(8):786–791
  92. Lamartiniere CA, Moore JB, Brown NM, et al. Genistein suppresses mammary cancer in rats. Carcinogenesis. 1995;16(11):2833–2840
  93. Jin Z, MacDonald RS. Soy isoflavones increase latency of spontaneous mammary tumours in mice. J Nutr. 2002;132(10):3186–3190
  94. Fischer L, Mahoney C, Jeffcoat AR, et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones, multiple-dose administration to men with prostate neoplasia. Nutr Cancer. 2004;48(2):160–170
  95. Takimoto CH, Glover K, Huang X, et al. Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(11 Pt 1):1213–1221
  96. Miltyk W, Craciunescu CN, Fischer L, et al. Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer. Am J Clin Nutr. 2003;77(4):875–882
  97. Busby MG, Jeffcoat AR, Bloedon LT, et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones, single-dose administration to healthy men. Am J Clin Nutr. 2002;75(1):126–136
  98. Bloedon LT, Jeffcoat AR, Lopaczynski W, et al. Safety and pharmacokinetics of purified soy isoflavones, single-dose administration to postmenopausal women. Am J Clin Nutr. 2002;76(5):1126–1137
  99. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood). 2002;227(10):852–859
  100. Giovannucci E, Rimm EB, Liu Y, et al. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002;94(5):391–398
  101. Chen L, Stacewicz-Sapuntzakis M, Duncan C, et al. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst. 2001;93(24):1872–1879
  102. Herzog A, Siler U, Spitzer V, et al. Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate. FASEB J. 2005;19(2):272–274
  103. Siler U, Barella L, Spitzer V, et al. Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model. FASEB J. 2004;18(9):1019–1021
  104. Kucuk O, Sarkar FH, Djuric Z, et al. Effects of lycopene supplementation in patients with localized prostate cancer. Exp Biol Med (Maywood). 2002;227(10):881–885
  105. Michnovicz JJ, Bradlow HL. Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J Natl Cancer Inst. 1990;82(11):947–949
  106. Newfield L, Goldsmith A, Bradlow HL, et al. Estrogen metabolism and human papillomavirus-induced tumours of the larynx, chemo-prophylaxis with indole-3-carbinol. Anticancer Res. 1993;13(2):337–341
  107. Coll DA, Rosen CA, Auborn K, et al. Treatment of recurrent respiratory papillomatosis with indole-3-carbinol. Am J Otolaryngol. 1997;18(4):283–285
  108. Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis, long-term results. J Voice. 2004;18(2):248–253
  109. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000;78(2):123–129
  110. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995;15(3):709–716
  111. Kojima T, Tanaka T, Mori H. Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res. 1994;54(6):1446–1449
  112. Jin L, Qi M, Chen DZ, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999;59(16):3991–3997
  113. El-Bayoumy K, Upadhyaya P, Desai DH, et al. Effects of 1;4-phenylenebis(methylene)selenocyanate, phenethyl isothiocyanate, indole-3-carbinol, and d-limonene individually and in combination on the tumourigenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Anticancer Res. 1996;16(5A):2709–2712
  114. Stoner G, Casto B, Ralston S, et al. Development of a multi-organ rat model for evaluating chemopreventive agents, efficacy of indole-3-carbinol. Carcinogenesis. 2002;23(2):265–272
  115. Grose KR, Bjeldanes LF. Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol. 1992;5(2):188–193
  116. Arneson DWHA, McMahon LM, Robaugh D. Presence of 3,3′-diindolylmethane in human plasma after oral administration of indole-3-carbinol. Proc Am Assoc Cancer Res. 1999;40:
  117. McDougal A, Sethi Gupta M, Ramamoorthy K, et al. Inhibition of carcinogen-induced rat mammary tumour growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Lett. 2000;151(2):169–179
  118. Le HT, Schaldach CM, Firestone GL, et al. Plant-derived 3,3′-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003;278(23):21136–21145
  119. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218–220
  120. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol, role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 2002;62(17):4945–4954
  121. Bhat KP, Lantvit D, Christov K, et al. Estrogenic and antiestrogenic properties of resveratrol in mammary tumour models. Cancer Res. 2001;61(20):7456–7463
  122. Bhat KPL, Kosmeder JW, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001;3(6):1041–1064
  123. Gusman J, Malonne H, Atassi G. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis. 2001;22(8):1111–1117
  124. Joe AK, Liu H, Suzui M, et al. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 2002;8(3):893–903
  125. Schneider Y, Duranton B, Gosse F, et al. Resveratrol inhibits intestinal tumourigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutr Cancer. 2001;39(1):102–107
  126. Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappaB, activator protein-1, and apoptosis, potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol. 2000;164(12):6509–6519
  127. She QB, Huang C, Zhang Y, et al. Involvement of c-jun NH(2)-terminal kinases in resveratrol-induced activation of p53 and apoptosis. Mol Carcinog. 2002;33(4):244–250
  128. Adhami VM, Afaq F, Ahmad N. Involvement of the retinoblastoma (pRb)-E2F/DP pathway during antiproliferative effects of resveratrol in human epidermoid carcinoma (A431) cells. Biochem Biophys Res Commun. 2001;288(3):579–585
  129. Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000;59(7):865–870
  130. Surh YJ, Chun KS, Cha HH, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals, down-regulation of COX-2 and iNOS through suppression of NF-kappaB activation. Mutat Res. 2001;480–481:243–268
  131. Fremont L. Biological effects of resveratrol. Life Sci. 2000;66(8):663–673
  132. Docherty JJ, Smith JS, Fu MM, et al. Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antiviral Res. 2004;61(1):19–26
  133. Gehm BD, McAndrews JM, Chien PY, et al. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA. 1997;94(25):14138–14143
  134. Ramsey TL, Risinger KE, Jernigan SC, et al. Estrogen receptor beta isoforms exhibit differences in ligand-activated transcriptional activity in an estrogen response element sequence-dependent manner. Endocrinology. 2004;145(1):149–160
  135. Harris HA, Albert LM, Leathurby Y, et al. Evaluation of an estrogen receptor-beta agonist in animal models of human disease. Endocrinology. 2003;144(10):4241–4249
  136. Gustafsson JA. What pharmacologists can learn from recent advances in estrogen signalling. Trends Pharmacol Sci. 2003;24(9):479–485
  137. Paruthiyil S, Parmar H, Kerekatte V, et al. Estrogen receptor beta inhibits human breast cancer cell proliferation and tumour formation by causing a G2 cell cycle arrest. Cancer Res. 2004;64(1):423–428
  138. Weihua Z, Andersson S, Cheng G, et al. Update on estrogen signaling. FEBS Lett. 2003;546(1):17–24
  139. Dotzlaw H, Leygue E, Watson PH, et al. Expression of estrogen receptor-beta in human breast tumours. J Clin Endocrinol Metab. 1997;82(7):2371–2374
  140. Latil A, Bieche I, Vidaud D, et al. Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Cancer Res. 2001;61(5):1919–1926
  141. Foley EF, Jazaeri AA, Shupnik MA, et al. Selective loss of estrogen receptor beta in malignant human colon. Cancer Res. 2000;60(2):245–248
  142. Brandenberger AW, Tee MK, Jaffe RB. Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ovarian serous cystadenocarcinoma and ovarian cancer cell lines, down-regulation of ER-beta in neoplastic tissues. J Clin Endocrinol Metab. 1998;83(3):1025–1028
  143. Akgun H, Lechago J, Younes M. Estrogen receptor-beta is expressed in Barrett’s metaplasia and associated adenocarcinoma of the esophagus. Anticancer Res. 2002;22(3):1459–1461
  144. Horvath LG, Henshall SM, Lee CS, et al. Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res. 2001;61(14):5331–5335
  145. Pasquali D, Rossi V, Esposito D, et al. Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues. J Clin Endocrinol Metab. 2001;86(5):2051–2055
  146. Fixemer T, Remberger K, Bonkhoff H. Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate. 2003;54(2):79–87
  147. Tsurusaki T, Aoki D, Kanetake H, et al. Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia. J Clin Endocrinol Metab. 2003;88(3):1333–1340
  148. Nojima D, Li LC, Dharia A, et al. CpG hypermethylation of the promoter region inactivates the estrogen receptor-beta gene in patients with prostate carcinoma. Cancer. 2001;92(8):2076–2083
  149. Sasaki M, Tanaka Y, Perinchery G, et al. Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer. J Natl Cancer Inst. 2002;94(5):384–390
  150. Zhu X, Leav I, Leung YK, et al. Dynamic regulation of estrogen receptor-beta expression by DNA methylation during prostate cancer development and metastasis. Am J Pathol. 2004;164(6):2003–2012
  151. Linja MJ, Savinainen KJ, Tammela TL, et al. Expression of ERalpha and ERbeta in prostate cancer. Prostate. 2003;55(3):180–186
  152. Leav I, Lau KM, Adams JY, et al. Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol. 2001;159(1):79–92
  153. Fujimura T, Takahashi S, Urano T, et al. Differential expression of estrogen receptor beta (ERbeta) and its C-terminal truncated splice variant ERbetacx as prognostic predictors in human prostatic cancer. Biochem Biophys Res Commun. 2001;289(3):692–699
  154. Kensler TW, Egner PA, Wang JB, et al. Strategies for chemoprevention of liver cancer. Eur J Cancer Prev. 2002;11(Suppl. 2):S58–S64
  155. Nelson WG, De Marzo AM, DeWeese TL. The molecular pathogenesis of prostate cancer. Implications for prostate cancer prevention. Urology. 2001;57(4 Suppl. 1):39–45
  156. Cai H, Hudson EA, Mann P, et al. Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo. Br J Cancer. 2004;91(7):1364–1371
  157. Ip C, Dong Y, Ganther HE. New concepts in selenium chemoprevention. Cancer Metastasis Rev. 2002;21(3–4):281–289
  158. Posner GH, Woodard BT, Crawford KR, et al. 2,2-Disubstituted analogues of the natural hormone 1 alpha,25-dihydroxyvitamin D(3), chemistry and biology. Bioorg Med Chem. 2002;10(7):2353–2365
  159. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44(1):235–249
  160. Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26
  161. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70
  162. Cheng J, Imanishi H, Liu W, et al. Involvement of cell cycle regulatory proteins and MAP kinase signaling pathway in growth inhibition and cell cycle arrest by a selective cyclooxygenase 2 inhibitor, etodolac, in human hepatocellular carcinoma cell lines. Cancer Sci. 2004;95(8):666–673
  163. Wu T, Leng J, Han C, et al. The cyclooxygenase-2 inhibitor celecoxib blocks phosphorylation of Akt and induces apoptosis in human cholangiocarcinoma cells. Mol Cancer Ther. 2004;3(3):299–307
  164. Dannenberg AJ, Lippman SM, Mann JR, et al. Cyclooxygenase-2 and epidermal growth factor receptor, pharmacologic targets for chemoprevention. J Clin Oncol. 2005;23(2):254–266
  165. Kyle E, Neckers L, Takimoto C, et al. Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol Pharmacol. 1997;51(2):193–200
  166. Henderson BE, Ross RK, Shibata A, et al. Environmental carcinogens and anticarcinogens. In:  Wattenberg L,  Lipkin M,  Boone CW, et al. editor. Cancer chemoprevention. Boca Raton (FL): CRC Press; 1992;p. 3–17
  167. Sharma S, Stutzman JD, Kelloff GJ, et al. Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer Res. 1994;54(22):5848–5855
  168. Prochaska HJ, Santamaria AB. Direct measurement of NAD (P)H,quinone reductase from cells cultured in microtiter wells, a screening assay for anticarcinogenic enzyme inducers. Anal Biochem. 1988;169(2):328–336
  169. Wattenberg LW. Inhibitors of chemical carcinogenesis. Adv Cancer Res. 1978;26:197–226
  170. Bertram B, Frei E, Wiessler M. Influence of disulfiram on glutathione, glutathione-S-transferase, and on nitrosamine-dealkylases of liver, kidney and esophagus. Biochem Pharmacol. 1985;34:387–388
  171. Kelloff GJ, Fay JR, Steele VE, et al. Epidermal growth factor receptor tyrosine kinase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev. 1996;5(8):657–666
  172. Fry DW, Kraker AJ, McMichael A, et al. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science. 1994;265(5175):1093–1095
  173. Weinstein IB, Arcoleo J, Backer J, et al. Molecular mechanisms of tumour promotion and multistage carcinogenesis. Princess Takamatsu Symp. 1983;14:59–74
  174. Kim TE, Murren JR. Lapatinib ditosylate GlaxoSmithKline. IDrugs. 2003;6(9):886–893
  175. Perchellet JP, Owen MD, Posey TD, et al. Inhibitory effects of glutathione level-raising agents and d-alpha-tocopherol on ornithine decarboxylase induction and mouse skin tumour promotion by 12-O-tetradecanoylphorbol-13-acetate. Carcinogenesis. 1985;6(4):567–573
  176. Lichti U, Patterson E, Hennings H, et al. Differential retinoic acid inhibition of ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate and by germicidal ultraviolet light. Cancer Res. 1981;41(1):49–54
  177. Pegg AE, Shantz LM, Coleman CS. Ornithine decarboxylase as a target for chemoprevention. J Cell Biochem Suppl. 1995;22:132–138
  178. Sharma S, Ghoddoussi M, Gao P, et al. A quantitative angiogenesis model for efficacy testing of chemopreventive agents. Anticancer Res. 2001;21(6A):3829–3837
  179. Compton MM. A biochemical hallmark of apoptosis, internucleosomal degradation of the genome. Cancer Metastasis Rev. 1992;11(2):105–119
  180. Schmid I, Uittenbogaart CH, Keld B, et al. A rapid method for measuring apoptosis and dual-color immunofluorescence by single laser flow cytometry. J Immunol Methods. 1994;170(2):145–157
  181. Lotan R. Roles of retinoids and their nuclear receptors in the development and prevention of upper aerodigestive tract cancers. Environ Health Perspect. 1997;105(Suppl. 4):985–988
  182. Muccio DD, Brouillette WJ, Alam M, et al. Conformationally defined 6-s-trans-retinoic acid analogs. 3. Structure–activity relationships for nuclear receptor binding, transcriptional activity, and cancer chemopreventive activity. J Med Chem. 1996;39(19):3625–3635
  183. Steele VE, Boone CW, Lubet RA, et al. Preclinical drug development paradigms for chemopreventives. Hematol Oncol Clin North Am. 1998;12(5):943–961v–vi
  184. Shay JW, Werbin H, Wright WE. Telomerase assays in the diagnosis and prognosis of cancer. Ciba Found Symp. 1997;211:148–155discussion 155–159
  185. Boone CW, Lieberman R, Mairinger T, et al. Computer-assisted image analysis-derived intermediate endpoints. Urology. 2001;57(4 Suppl. 1):1129–1131
  186. Bogdanov AA, Lin CP, Simonova M, et al. Cellular activation of the self-quenched fluorescent reporter probe in tumour microenvironment. Neoplasia. 2002;4(3):228–236
  187. Rafferty TS, Green MH, Lowe JE, et al. Effects of selenium compounds on induction of DNA damage by broadband ultraviolet radiation in human keratinocytes. Br J Dermatol. 2003;148(5):1001–1009
  188. Stoyanova R, Clapper ML, Bellacosa A, et al. Altered gene expression in phenotypically normal renal cells from carriers of tumour suppressor gene mutations. Cancer Biol Ther. 2004;3(12):1313–1321
  189. Arnold JT, Wilkinson BP, Sharma S, et al. Evaluation of chemopreventive agents in different mechanistic classes using a rat tracheal epithelial cell culture transformation assay. Cancer Res. 1995;55(3):537–543
  190. Korytynski EA, Kelloff GJ, Suk WA, et al. The development of an anchorage-independence assay using human lung tumour cells to screen potential chemopreventive agents. Anticancer Res. 1996;16(3A):1091–1094
  191. Mehta RG, Steele V, Kelloff GJ, et al. Influence of thiols and inhibitors of prostaglandin biosynthesis on the carcinogen-induced development of mammary lesions in vitro. Anticancer Res. 1991;11(2):587–591
  192. Steele VE, Sharma S, Mehta R, et al. Use of in vitro assays to predict the efficacy of chemopreventive agents in whole animals. J Cell Biochem Suppl. 1996;26:29–53
  193. Bern HA, Nandi S. Recent studies of the hormonal influence in mouse mammary tumourigenesis. Prog Exp Tumour Res. 1961;2:90–144
  194. Normann TC. Neurosecretion by exocytosis. Int Rev Cytol. 1976;46:1–77
  195. Wood BG, Washburn LL, Mukherjee AS, et al. Hormonal regulation of lobulo-alveolar growth, functional differentiation and regression of whole mouse mammary gland in organ culture. J Endocrinol. 1975;65(1):1–6
  196. Thompson HJ, McGinley JN, Rothhammer K, et al. Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis. 1995;16(10):2407–2411
  197. Bird RP. Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen, preliminary findings. Cancer Lett. 1987;37(2):147–151
  198. Pereira MA, Barnes LH, Rassman VL, et al. Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis. 1994;15(5):1049–1054
  199. Steele VE, Moon RC, Lubet RA, et al. Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models, methods and results from the NCI Chemoprevention Drug Development Program. J Cell Biochem Suppl. 1994;20:32–54
  200. Stoner GD. Lung tumours in strain A mice as a bioassay for carcinogenicity of environmental chemicals. Exp Lung Res. 1991;17(2):405–423
  201. Lubet R, Wang Y, Zhang Z, et al. Mouse models incorporating alterations in the major tumour suppressor genes P53 and P16, their use in screening for potential carcinogens, developing further relevant mouse models, and screening for potential chemopreventive and chemotherapetutic agents. Exp Lung Res. 2005;31(1):117–133
  202. Estensen RD, Jordan MM, Wiedmann TS, et al. Effect of chemopreventive agents on separate stages of progression of benzo[a]pyrene induced lung tumours in A/J mice. Carcinogenesis. 2004;25(2):197–201
  203. Moon RC, Rao KV, Detrisac CJ, et al. Hamster lung cancer model of carcinogenesis and chemoprevention. Adv Exp Med Biol. 1992;320:55–61
  204. Solt DB, Chang K, Helenowski I, et al. Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention. Cancer Lett. 2003;202(2):147–152
  205. Gerson SJ. Oral cancer. Crit Rev Oral Biol Med. 1990;1(3):153–166
  206. Tanaka T, Makita H, Ohnishi M, et al. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary curcumin and hesperidin, comparison with the protective effect of beta-carotene. Cancer Res. 1994;54(17):4653–4659
  207. Boone CW, Kelloff GJ, Malone WE. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials, a review. Cancer Res. 1990;50(1):2–9
  208. Su LK, Kinzler KW, Vogelstein B, et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992;256(5057):668–670
  209. Edelmann W, Yang K, Kuraguchi M, et al. Tumourigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res. 1999;59(6):1301–1307
  210. Cooper HS, Everley L, Chang WC, et al. The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis. Gastroenterology. 2001;121(6):1407–1416
  211. Cooper HS, Murthy S, Kido K, et al. Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human, a study of histopathology, B-catenin and p53 expression and the role of inflammation. Carcinogenesis. 2000;21(4):757–768
  212. Goldstein SR, Yang GY, Curtis SK, et al. Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen. Carcinogenesis. 1997;18(11):2265–2270
  213. Clark GW, Smyrk TC, Mirvish SS, et al. Effect of gastroduodenal juice and dietary fat on the development of Barrett’s esophagus and esophageal neoplasia, an experimental rat model. Ann Surg Oncol. 1994;1(3):252–261
  214. Moon RC, Mehta RG. Chemoprevention of experimental carcinogenesis in animals. Prev Med. 1989;18(5):576–591
  215. McCormick DL, Adamowski CB, Fiks A, et al. Lifetime dose-response relationships for mammary tumour induction by a single administration of N-methyl-N-nitrosourea. Cancer Res. 1981;41(5):1690–1694
  216. Moon RC, Kelloff GJ, Detrisac CJ, et al. Chemoprevention of MNU-induced mammary tumours in the mature rat by 4-HPR and tamoxifen. Anticancer Res. 1992;12(4):1147–1153
  217. Maroulakou IG, Anver M, Garrett L, et al. Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumour antigen fusion gene. Proc Natl Acad Sci USA. 1994;91(23):11236–11240
  218. Gould MN. The introduction of activated oncogenes to mammary cells in vivo using retroviral vectors, a new model for the chemoprevention of premalignant and malignant lesions of the breast. J Cell Biochem Suppl. 1993;17G:66–72
  219. Bosland MC. Use of animal models in defining efficacy of chemoprevention agents against prostate cancer. Eur Urol. 1999;35(5–6):459–463
  220. Greenberg NM, DeMayo F, Finegold MJ, et al. Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA. 1995;92(8):3439–3443
  221. Becci PJ, Thompson HJ, Strum JM, et al. N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder cancer in C57BL/6 X DBA/2 F1 mice as a useful model for study of chemoprevention of cancer with retinoids. Cancer Res. 1981;41(3):927–932
  222. McCormick DL, Moon RC. Antipromotional activity of dietary N-(4-hydroxyphenyl)retinamide in two-stage skin tumourigenesis in CD-1 and SENCAR mice. Cancer Lett. 1986;31(2):133–138
  223. Warren BS, Slaga TJ. Mechanisms of inhibition of tumour progression. Basic Life Sci. 1993;61:279–289
  224. DiGiovanni J. Multistage carcinogenesis in mouse skin. Pharmacol Ther. 1992;54(1):63–128
  225. Forbes PD, Beer JZ, Black HS, et al. Standardized protocols for photocarcinogenesis safety testing. Front Biosci. 2003;8:d848–d854
  226. Arbeit JM. Mouse models of cervical cancer. Comp Med. 2003;53(3):256–258
  227. Nishida T, Sugiyama T, Kataoka A, et al. Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7,12-dimethylbenz[a]anthracene-coated suture, common epithelial tumours of the ovary in rats. Cancer. 1998;83(5):965–970
  228. Fredrickson TN. Ovarian tumours of the hen. Environ Health Perspect. 1987;73:35–51
  229. Sivaraman L, Gay J, Hilsenbeck SG, et al. Effect of selective ablation of proliferating mammary epithelial cells on MNU induced rat mammary tumourigenesis. Breast Cancer Res Treat. 2002;73(1):75–83
  230. Li Y, Welm B, Podsypanina K, et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA. 2003;100(26):15853–15858
  231. Smalley M, Ashworth A. Stem cells and breast cancer, a field in transit. Nat Rev Cancer. 2003;3(11):832–844
  232. Dick JE. Breast cancer stem cells revealed. Proc Natl Acad Sci USA. 2003;100(7):3547–3549
  233. Welm BE, Tepera SB, Venezia T, et al. Sca-1 (pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol. 2002;245(1):42–56
  234. Wax A, Yang C, Muller MG, et al. In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry. Cancer Res. 2003;63(13):3556–3559
  235. Kelloff GJ, Johnson JR, Crowell JA, et al. Approaches to the development and marketing approval of drugs that prevent cancer. Cancer Epidemiol Biomarkers Prev. 1995;4(1):1–10
  236. Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumours. N Engl J Med. 1989;320(8):479–484
  237. Fisher B, Powles TJ, Pritchard KJ. Tamoxifen for the prevention of breast cancer. Eur J Cancer. 2000;36(2):142–150
  238. Drazen JM. COX-2 inhibitors – a lesson in unexpected problems. N Engl J Med. 2005;352(11):1131–1132
  239. Psaty BM, Furberg CD. COX-2 inhibitors – lessons in drug safety. N Engl J Med. 2005;352(11):1133–1135

PII: S0959-8049(05)00339-4

doi: 10.1016/j.ejca.2005.04.016

European Journal of Cancer
Volume 41, Issue 13 , Pages 1889-1910 , September 2005

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