EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium

Journal of Steroid Biochemistry and Molecular Biology

Volumn 69, Issue 1-6, 1999, Pages 51-84

  Labrie, Fernand ^a   Labrie, Claude ^a   Bélanger, Alain ^a   Simard, Jacques ^a   Gauthier, Sylvain ^a   Luu The, Van ^a   Mérand, Yves ^a   Giguere, Vincent ^a   Candas, Bernard ^a   Luo, Shouqi ^a   Martel, Céline ^a   Singh, Shankar Mohan ^a   Fournier, Marc ^a   Coquet, Agnès ^a   Richard, Virgile ^a   Charbonneau, Ronald ^a   Charpenet, Gilles ^a   Tremblay, André ^a   Tremblay, Gilles ^a   Cusan, Lionel ^a   Veilleux, Raymonde ^a   more..

^a LAVAL UNIVERSITY   (Canada)

Author keywords

Adjuvant; Breast cancer; Cholesterol; EM 800; EM 652; Neoadjuvant; Osteoporosis; Prevention; Pure antiestrogen; Risk reduction; SCH 57050; SCH 57068; Selective estrogen receptor modulator (SERM); Triglycerides; Uterine cancer

Indexed keywords

4 [4 METHYL 2 [4 [2 (1 PIPERIDINYL)ETHOXY]PHENYL] 7 PIVALOYLOXY 2H 1 BENZOPYRAN 3 YLPHENYL] PIVALATE; ACOLBIFENE; ALKALINE PHOSPHATASE; AMINO ACID; ANASTROZOLE; CHOLESTEROL; DIMETHYLBENZ[A]ANTHRACENE; DROLOXIFENE; ESTRADIOL; ESTROGEN RECEPTOR; FULVESTRANT; GESTAGEN; GROWTH FACTOR; HYDROXYTAMOXIFEN; LIPID; MEDROXYPROGESTERONE; MITOGEN ACTIVATED PROTEIN KINASE; N BUTYL 11 (3,17BETA DIHYDROXYESTRA 1,3,5(10) TRIEN 7ALPHA YL) N METHYLUNDECANAMIDE; PRASTERONE; PRASTERONE SULFATE; PROTEIN KINASE; RALOXIFENE; STEROID RECEPTOR; TAMOXIFEN; TOREMIFENE; TRIACYLGLYCEROL;

AMINO ACID SEQUENCE; BONE ATROPHY; BONE DENSITY; BONE MINERAL; BREAST CANCER; CLINICAL TRIAL; CONFERENCE PAPER; DOSE RESPONSE; DRUG POTENCY; ENDOMETRIUM; ESTROGEN THERAPY; HUMAN; MAMMARY GLAND; NONHUMAN; ORAL DRUG ADMINISTRATION; OSTEOPOROSIS; UTERUS CANCER;

ANIMALS; BREAST NEOPLASMS; ENDOMETRIAL NEOPLASMS; ENDOMETRIUM; ESTROGEN ANTAGONISTS; FEMALE; HUMANS; MAMMARY GLANDS, ANIMAL; PIPERIDINES;

EID: 0033051859     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-0760(99)00065-5     Document Type: Conference Paper

References (224)

1. Landis S.H., Murray T., Bolden S., Wingo P.A. Cancer Statistics, 1999. CA Cancer J. Clin. 49:1999;8-31.
2. Mouridsen H., Palshof T., Patterson J., Battersby L. Tamoxifen in advanced breast cancer. Cancer Treat. Rev. 5:1978;131-141.
3. Dickson R.B., Lippman M.E. Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma. Endocr. Rev. 8:1987;29-43.
4. Horwitz K.B., McGuire W.L. Nuclear mechanism of estrogen action. Effects of estradiol and anti-estrogens on estrogen receptors and nuclear receptor processing. J. Biol. Chem. 253:1978;8185-8191.
5. Wakeling A.E. The future of new pure antiestrogens in clinical breast cancer. Breast Cancer Res. Treat. 25:1993;1-9.
6. Asselin J., Labrie F. Effects of estradiol and prolactin on steroid receptor levels in 7,12-dimethylbenz(a)anthracene-induced mammary tumors and uterus in the rat. J. Steroid Biochem. 9:1978;1079-1082.
7. McGuire W.L., Carbone P.P., Seard M.E., Esche G.C. Estrogen receptors in human breast cancer: an overview. McGuire W.L., Carbone P.P., Vollmer E.P. Estrogen receptors in human breast cancer. 1975;1-7 Raven Press, New York.
8. Davidson N.E., Lippman M.E. The role of estrogens in growth regulation of breast cancer. Crit. Rev. Oncog. 1:1989;89-111.
9. Dowsett M., Macaulay V., Gledhill J., Ryde C., Nicholls J., Ashworth A., McKinna J.A., Smith I.E. Control of aromatase in breast cancer cells and its importance for tumor growth. J. Steroid Biochem. Molec. Biol. 44:1993;605-609.
10. Miller W.R. Fundamental research leading to improved endocrine therapy for breast cancer. J. Steroid Biochem. 27:1987;477-485.
11. Labrie F. Intracrinology. Molec. Cell. Endocr. 78:1991;C113-C118.
12. Labrie F., Bélanger A., Simard J., Luu-The V., Labrie C. DHEA and peripheral androgen and estrogen formation: Intracrinology. Ann. N.Y. Acad. Sci. 774:1995;16-28.
13. Labrie F., Simard J., Luu-The V., Bélanger A., Pelletier G., Morel Y., Mebarki F., Sanchez R., Durocher F., Turgeon C., Labrie Y., Rhéaume E., Labrie C., Lachance Y. The 3β-hydroxysteroid dehydrogenase/isomerase gene family: lessons from type II 3β-HSD congenital deficiency. Hansson V., Levy F.O., Taskén K. Signal Transduction in Testicular Cells. Ernst Schering Research Foundation Workshop. 1996;185-218 Springer-Verlag, Berlin.
14. de Launoit Y., Dauvois S., Dufour M., Simard J., Labrie F. Inhibition of cell cycle kinetics and proliferation by the androgen 5α-dihydrotestosterone and antiestrogen N, n-butyl-N-methyl-11-(16′α-chloro-3′,17β-dihydroxy-estra- 1′,3′,5′-(10′)triene- 7′α-yl)undecanamide in human breast cancer ZR-75-1 cells. Cancer Res. 51:1991;2797-2802.
15. Dauvois S., Geng C.S., Lévesque C., Mérand Y., Labrie F. Additive inhibitory effects of an androgen and the antiestrogen EM-170 on estradiol-stimulated growth of human ZR-75-1 breast tumors in athymic mice. Cancer Res. 51:1991;3131-3135.
16. Lévesque C., Mérand Y., Dufour J.M., Labrie C., Labrie F. Synthesis and biological activity of new halo-steroidal antiestrogens. J. Med. Chem. 34:1991;1624-1630.
17. Labrie F., Li S., Labrie C., Lévesque C., Mérand Y. Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12 dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Breast Cancer Res. Treat. 33:1995;237-244.
18. Wakeling A.E., Bowler J. Biology and mode of action of pure antiestrogens. J. Steroid Biochem. 30:1988;141-147.
19. Labrie C., Martel C., Dufour J.M., Lévesque C., Mérand Y., Labrie F. Novel compounds inhibit estrogen formation and action. Cancer Res. 52:1992;610-615.
20. Gronemeyer H., Benhamou B., Berry M., Bocquel M.T., Gofflo D., Garcia T., Lerouge T., Metzger D., Meyer M.E., Tora L., Vergezac A., Chambon P. Mechanisms of antihormone action. J. Steroid Biochem. Molec. Biol. 41:1992;217-221.
21. Green S., Walter P., Kumar V., Krust V., Bornert J.M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 320:1986;134-139.
22. Kumar V., Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell. 55:1988;145-156.
23. Furr B.J., Jordan V.C. The pharmacology and clinical uses of tamoxifen. Pharmacol. Ther. 25:1984;127-205.
24. Cole M.P., Jones C.T., Todd I.D. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br. J. Cancer. 25:1971;270-275.
25. Ingle J.N., Ahmann D.L., Green S.J., Edmonson J.H., Bisel H.F., Kvols L.K., et al. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N. Engl. J. Med. 304:1981;16-21.
26. Buchanan R.B., Blamey R.W., Durrant K.R., Howell A., Paterson A.G., Smith D.C., Williams C.J., Wilson R.G. A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J. Clin. Oncol. 4:1986;1326-1330.
27. Howell A., Dodwell D.J., Laidlaw I., Anderson H., Anderson E. Tamoxifen as an agonist for metastatic breast cancer. Goldhirsch A. Endocrine therapy of breast cancer IV. 1990;Springer-Verlag, Berlin.
28. Poulin R., Mérand Y., Poirier D., Lévesque C., Dufour J.M., Labrie F. Antiestrogenic properties of keoxifene, trans-4-hydroxytamoxifen and ICI164384, a new steroidal antiestrogen, in ZR-75-1 human breast cancer cells. Breast Cancer Res. Treat. 14:1989;65-76.
29. Gottardis M.M., Robinson S.P., Satyaswaroop P.G., Jordan V.C. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Res. 48:1988;812-815.
30. Chalbos D., Philips A., Galtier F., Rochefort H. Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3′,5′-monophosphate in MCF7 cells. Endocrinology. 133:1993;571-576.
31. Canney P.A., Griffiths T., Latief T.N., Priestman T.J. Clinical significance of Tamoxifen withdrawal response. Lancet. 1:1987;36.
32. Howell A., Dodwell D.J., Anderson H., Redford J. Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. Ann. Oncol. 3:1992;611-617.
33. Thompson E.W., Katz D., Shima T.B., Wakeling A.E., Lippman M.E., Dickson R. ICI 164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness. Cancer Res. 49:1989;6929-6934.
34. Roos W., Huber P., Oeze L., Eppenberger U. Hormone dependency and the action of tamoxifen in human mammary carcinoma cells. Anticancer Res. 2:1982;157-162.
35. Reddel R.R., Sutherland R.L. Tamoxifen stimulation of human breast cancer cell proliferation in vitro: A possible model for tamoxifen tumour flare. Eur. J. Cancer Clin. Oncol. 20:1984;1419-1424.
36. Darbre P.D., Curtis S., King R.J. Effects of estradiol and tamoxifen on human breast cancer cells in serum-free culture. Cancer Res. 44:1984;2790-2793.
37. Katzenellenbogen B.S., Kendra K.L., Norman M.J., Berthois Y. Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res. 47:1987;4355-4360.
38. Poulin R., Baker D., Poirier D., Labrie F. Androgen and glucocorticoid receptor-mediated inhibition of cell proliferation by medroxyprogesterone acetate in ZR-75-1 human breast cancer cells. Breast Cancer Res. Treat. 13:1989;161-172.
39. Wakeling A.E., Newboult E., Peters S.W. Effects of antioestrogens on the proliferation of MCF-7 human breast cancer cells. J. Molec. Endocr. 2:1989;225-234.
40. DeFriend D.J., Howell A., Nicholson R.I., Anderson E., Dowsett M., Mansel R.E., Blamey R.W., Bundred N.J., Robertson J.F., Saunders C., Baum M., Walton P., Sutcliffe F., Wakeling A.E. Investigation of a pure antiestrogen ICI182780 in women with primary breast cancer. Cancer Res. 54:1994;408-414.
41. Killackey M.A., Hakes T.B., Pierce V.K. Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treatment Reports. 69:1985;237-238.
42. Hardell L. Tamoxifen as risk factor for carcinoma of corpus uteri. Lancet. 3:1988;563.
43. Jordan V.C. Tamoxifen and endometrial cancer. Lancet. 2:1988;1019.
44. Neven P., DeMuylder X., VanBelle Y. Tamoxifen and the uterus and endometrium. Lancet. 1:1989;375-376.
45. Fornander T., Rutquist L.E., Cedermark B., Glas U., Mattsson A., Silfverswärd C., Skoog L., Somell A., Theve T., Wilking N., et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet. 1:1989;117-120.
46. Fornander T., Hellström A.C., Moberger B. Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer. J. Natl Cancer Inst. 85:1993;1850-1855.
47. Mathew A., Chabon A.B., Kabakow B., Drucker M., Hirschman R.J. Endometrial carcinoma in five patients with breast cancer on Tamoxifen therapy. N.Y. State J. Med. 90:1990;207-208.
48. Malfetano J.H. Tamoxifen-associated endometrial carcinoma in post-menopausal breast cancer patients. Gynecol. Oncol. 39:1990;82-84.
49. Magriples U., Naftolin F., Schwartz P.E., Carcangiu M.L. High-grade endometrial carcinoma in Tamoxifen-treated breast cancer patients. J. Clin. Oncol. 11:1993;485-490.
50. Andersson M., Storm H.H., Mouridsen H.T. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer. J. Natl Cancer Inst. 83:1991;1013-1017.
51. Atlante G., Pozzi M., Vincenzoni C., Vocaturo G. Four case reports presenting new acquisitions on the association between breast and endometrial carcinoma. Gynecol. Oncol. 37:1990;378-380.
52. Boudouris O., Ferrand S., Guillet J.L., Madelenat P. Effets paradoxaux du tamoxifène sur l'utérus de la femme. J. Gynecol. Obstet. Biol. Reprod. Paris. 18:1989;372-378.
53. Gusberg S.B. Tamoxifen for breast cancer: associated endometrial cancer. Cancer. 65:1990;1463-1464.
54. Nayfield S.G., Karp J.E., Ford L.G., Dorr F.A., Kramer B.S. Potential role of tamoxifen in prevention of breast cancer. J. Natl Cancer Inst. 83:1991;1450-1459.
55. Cohen I., Rosen D.J., Shapira J., Cordoba M., Gilboa S., Altaras M.M., Yigael D., Beyth Y. Endometrial changes in postmenopausal women treated with tamoxifen for breast cancer. Br. J. Obstet. Gynaecol. 100:1993;567-570.
56. Gauthier S., Caron B., Cloutier J., Dory Y.L., Favre A., Larouche D., Mailhot J., Ouellet C., Schwerdtfeger A., Leblanc G., Martel C., Simard J., Mérand Y., Bélanger A., Labrie C., Labrie F. (S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2- (1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl] 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active non steroidal antiestrogen. J. Med. Chem. 40:1997;2117-2122.
57. Simard J., Sanchez R., Poirier D., Gauthier S., Singh S.M., Mérand Y., Bélanger A., Labrie C., Labrie F. Blockade of the stimulatory effect of estrogens, OH-Tamoxifen, OH-Toremifene, Droloxifene and Raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells. Cancer Res. 57:1997;3494-3497.
58. Tormey D.C., Jordan V.C. Long-term tamoxifen adjuvant therapy in node-positive breast cancer: a metabolic and pilot clinical study. Breast Cancer Res. Treat. 4:1984;297-302.
59. Scottish Study. The Scottish trial. Lancet. ii:1987;171-175.
60. Powles T.J., Tillyer C.R., Jones A.L., Ashley S.E., Treleaven J., Davey J.B., McKinna J.A. Prevention of breast cancer with tamoxifen - an update on the Royal Marsden Hospital pilot programme. Eur. J. Cancer. 26:1990;680-684.
61. Fisher B., Costantino J.P., Lawrence Wickerham D., Redmond C.K., Kavanah M., Cronin W.M., Vogel V., Robidoux A., Dimitrov N., Atkins J., Daly M., Wieand S., Tan-Chiu E., Ford L., Wolmark N. Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J. Natl Cancer Inst. 90:1998;1371-1388.
62. Wakeling A.E., Dukes M., Bowler J. A potent specific pure antiestrogen with clinical potential. Cancer Res. 51:1991;3867-3873.
63. Wakeling A.E., Bowler J. ICI 182,780, a new antioestrogen with clinical potential. J. Steroid Biochem. Molec. Biol. 43:1992;173-177.
64. Simard J., Dauvois S., Haagensen D.E., Lévesque C., Mérand Y., Labrie F. Regulation of progesterone-binding breast cyst protein GCDFP-24 secretion by estrogens and androgens in human breast cancer cells: a new marker of steroid action in breast cancer. Endocrinology. 126:1990;3223-3231.
65. Tremblay G.B., Tremblay A., Copeland N.G., Gilbert D.J., Jenkins N.A., Labrie F., Giguere V. Cloning, chromosomal localization and functional analysis of the murine estrogen receptor? Molec. Endocr. 11:1997;353-365.
66. Giambiagi N., Pasqualini J.R. Studies on the activation of the oestrogen receptor bound to the anti-oestrogens 4-hydroxytamoxifen and ICI 164,384 by using three monoclonal antibodies. J. Molec. Endocr. 7:1991;9-19.
67. Chetrite G., Pasqualini J.G. Biological responses of ICI 164,384 and other antiestrogens in vaginal and uterine cells of fetal guinea pig in culture. Acta Endocr. Copenh. 125:1991;401-408.
68. Weaver C.A., Springer P.A., Katzenellenbogen B.S. Regulation of pS2 gene expression by affinity labeling and reversibly binding estrogens and antiestrogens: Comparison of effects on the native gene and on pS2-chloramphenicol acetyltransferase fusion genes transfected into MCF-7 human breast cancer cells. Molec. Endocr. 2:1988;936-945.
69. Luo S., Martel C., Gauthier S., Mérand Y., Bélanger A., Labrie C., Labrie F. Long term inhibitory effects of a novel antiestrogen on the growth of ZR-75-1 and MCF-7 human breast cancer tumors in nude mice. Int. J. Cancer. 73:1997;735-739.
70. Simard J., Labrie C., Bélanger A., Gauthier S., Singh S.M., Mérand Y., Labrie F. Characterization of the effects of the novel non-steroidal antiestrogen EM-800 on basal and estrogen-induced proliferation of T-47D, ZR-75-1 and MCF-7 human breast cancer cells in vitro. Int. J. Cancer. 73:1997;104-112.
71. Couillard S., Gutman M., Labrie C., Bélanger A., Candas B., Labrie F. Comparison of the effects of the antiestrogens EM-800 and Tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice. Cancer Res. 58:1998;60-64.
72. Couillard S., Labrie C., Bélanger A., Candas B., Pouliot F., Labrie F. Effect of dehydroepiandrosterone and the antiestrogen EM-800 on the growth of human ZR-75-1 breast cancer xenografts. J. Natl Cancer Inst. 90:1998;772-778.
73. Asselin J., Mélançon R., Moachon G., Bélanger A. Characteristics of binding to estrogen, androgen, progestin and glucocorticoid receptors in 7,12-dimethylbenz(a)anthracene-induced mammary tumors and their hormonal control. Cancer Res. 40:1980;1612-1622.
74. White R., Lees J.A., Needham M., Ham J., Parker M. Structural organization and expression of the mouse estrogen receptor. Molec. Endocr. 1:1987;735-744.
75. Greene G.L., Gilna P., Waterfield M., Baker A., Hort Y., Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science. 231:1986;1150-1154.
76. Kuiper G.G.J.M., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J.A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl Acad. Sci., USA. 93:1996;5925-5930.
77. Mosselman S., Polman J., Dijkema R. ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392:1996;49-53.
78. Krust A., Green S., Argos P., Kumar V., Walter P., Bornert J-M., Chambon P. The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. EMBO J. 5:1986;891-897.
79. Kumar V., Green S., Stack G., Berry M., Jin J.R., Chambon P. Functional domains of the human estrogen receptor. Cell. 51:1987;941-951.
80. Berry M., Metzger D., Chambon P. Role of the two activating domains of the oestrogen receptor in cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J. 9:1990;2811-2818.
81. Metzger D., Ali S., Bornert J.M., Chambon P. Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells. J. Biol. Chem. 270:1995;9535-9542.
82. Cavaillès V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P.J., Parker M.G. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 14:1995;3741-3751.
83. Halachmi S., Marden E., Martin G., MacKay H., Abbondanza C., Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science. 264:1994;1455-1458.
84. Horwitz K.B., Jackson T.A., Rain D.L., Richer J.K., Takimoto G.S., Tung L. Nuclear receptor coactivators and corepressors. Molec. Endocr. 10:1996;1167-1177.
85. Onate S.A., Tsai S.Y., Tsai M-J., O'Malley B.W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 270:1995;1354-1357.
86. Tora L., Mullick A., Metzger D., Ponglikitmongkol M., Park I., Chambon P. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 8:1989;1981-1986.
87. Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S.C., Heyman R.A., Rose D.W., Glass C.K., Rosenfeld M.G. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 85:1996;403-411.
88. Voegel J.J., Heine M.J.S., Zechel C., Chambon P., Gronemeyer H. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J. 15:1996;3667-3675.
89. Hong H., Kohli K., Trivedi A., Johnson D.L., Stallcup M.R. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc. Natl Acad. Sci., USA. 93:1996;4948-4952.
90. Anzick S.L., Kononen J., Walker R.L., Azorsa D.O., Tanner M.M., Guan X.Y., Sauter G., Kallioniemi O.P., Trent J.M., Meltzer P.S. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science. 277:1997;965-968.
91. Torchia J., Rose D.W., inostroza J., Kamei Y., Westin S., Glass C.K., Rosenfeld M.G. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 387:1997;677-684.
92. Chen H., Lin R.J., Schlitz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and form a multimeric activation complex with P/CAF and CBP/p300. Cell. 90:1997;569-580.
93. Li H., Gomes P.J., Chen J.D. RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc. Natl Acad. Sci., USA. 94:1997;8479-8484.
94. Ignar-Trowbridge D.M., Teng C.T., Ross K.A., Parker M.G., Korach K.S., McLachlan J.A. Peptide growth factors elicit estrogen receptor-dependent transcriptional activation of an estrogen-responsive element. Molec. Endocr. 7:1993;992-998.
95. Aronica S.M., Katzenellenbogen B.S. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Molec. Endocr. 7:1993;743-752.
96. Bunone G., Briand P.A., Miksicek R.J., Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphoryltion. EMBO J. 15:1996;2174-2183.
97. Power R.F., Mani S.K., Codina J., Conneley O.M., O'Malley B.W. Dopaminergic and ligand-independent activation of steroid hormone receptors. Science. 254:1991;1636-1639.
98. Smith C.L., Conneely O.M., O'Malley B.W. Modulation of the ligand-independent activation of the human estrogen receptor by hormone and antihormone. Proc. Natl Acad. Sci., USA. 90:1993;6120-6124.
99. Ali S., Metzger D., Bornert J.M., Chambon P. Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J. 12:1993;1153-1160.
100. Kato S., Endoh H., Masuhiro Y., Kitamoto T., Uchiyama S., Sasaki H., Masushige S., Gotoh Y., Nishida E., Kawashima H., Metzger D., Chambon P. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 270:1995;1491-1494.
101. Berry M., Nunez A.M., Chambon P. Estrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence. Proc. Natl Acad. Sci., USA. 86:1989;1218-1222.
102. McInerney E.M., Tsai M.J., O'Malley B.W., Katzenellenbogen B.S. Analysis of estrogen receptor transcriptional enhancement by a nuclear hormone receptor coactivator. Proc. Natl Acad. Sci., USA. 93:1996;10069-10073.
103. McInerney E.M., Katzenellenbogen B.S. Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcription activation. J. Biol. Chem. 271:1996;24172-24178.
104. Weigel N.L. Steroid hormone receptors and their regulation by phosphorylation. Biochem. J. 319:1996;657-667.
105. Tremblay A., Tremblay G.B., Labrie C., Labrie F., Giguère V. EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors α and β Endocrinology. 139:1998;111-118.
106. Takeshita A., Yen P.M., Misiti S., Cardona G.R., Liu Y., Chin W.W. Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. Endocrinology. 137:1996;3594-3597.
107. Henttu P.M., Kalkhoven E., Parker M.G. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Molec. Cell. Biol. 17:1997;1832-1839.
108. Jeyakumar M., Tanen M.R., Bagchi M.K. Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor. Molec. Endocr. 11:1997;755-767.
109. Tremblay G.B., Tremblay A., Labrie F., Giguère V. Dominant activity of activation function-1 (AF-1) and differential stoichiometric requirements for AF-1 and -2 in the estrogen receptor α-β heterodimeric complex. Molec. Cell. Biol. 19:1999;1919-1927.
110. Huggins C., Grand L.C., Brillantes F.P. Mammary cancer induced by a single feeding of polynuclear hydrocarbons, and its suppression. Nature. 189:1961;204-207.
111. Welsch C.W. Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins. Cancer Res. 45:1985;3415-3443.
112. Leung B.S., Sasaki G.H., Leung J.S. Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthacene-induced tumors. Cancer Res. 35:1975;621-627.
113. Asselin J., Kelly P.A., Caron M.G., Labrie F. Control of hormone receptor levels and growth of 7,12-dimethylbenz(a)anthracene-induced mammary tumors by estrogens, progesterone and prolactin. Endocrinology. 101:1977;666-671.
114. Li S., Lévesque C., Geng C.S., Yan X., Labrie F. Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen EM-219 on estrone (E1)-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Breast Cancer Res. Treat. 34:1995;147-159.
115. Labrie F., Li S., Bélanger A., Côté J., Mérand Y., Lepage M. Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the development of mammary tumors induced by dimethylbenz(a)anthracene in the rat. Breast Cancer Res. Treat. 26:1993;253-265.
116. Kelly P.A., Asselin J., Labrie F. Endocrine regulation of growth and hormone receptor levels in DMBA-induced mammary tumors. Thompson E.B., Lippman M.E. Steroids receptors and the management of cancer. 1979;3-29 CRC Press, Boca Raton, Fl.
117. Kelly P.A., Asselin J., Caron M.G., Raynaud J.P., Labrie F. High inhibitory activity of a new antiestrogen, RU16117 (11α-methoxy-ethinyl estradiol) on the development of dimethylbenz(a)anthracene-induced mammary tumors. Cancer Res. 37:1977;76-81.
118. Dauvois S., Labrie F. Effect of adrenal estrogens on the growth of dimethylbenz(a)antracene-induced mammary carcinoma in the rat. Bradlow L.C.H., d'Aquino S., Labrie F. Steroid Formation, Degradation and Action in Peripheral Tissues, Normal and Neoplastic Tissues. Ann. New York Acad. Sci. 1990;416-418.
119. Dauvois S., Spinola P.G., Labrie F. Additive inhibitory effects of bromocriptine (CB-154) and medroxyprogesterone acetate (MPA) on dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat. Eur. J. Cancer Clin. Oncol. 25:1989;891-897.
120. Labrie F., Kelly P.A., Asselin J., Raynaud J.P. Potent inhibitory activity of a new antiestrogen, RU16117, on the development and growth of DMBA-induced rat mammary adenocarcinoma. Band G., Israel L. Breast Cancer, A Multidisciplinary Approach. Recent Results in Cancer Research. 1976;109-120 Springer-Verlag, New York.
121. Jordan V.C., Allen K.E. Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA-induced rat mammary carcinoma model. Eur. J. Cancer. 16:1980;239-251.
122. Li S., Yan X., Bélanger A., Labrie F. Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in the rat. Breast Cancer Res. Treat. 29:1993;203-217.
123. Luo S., Martel C., Sourla A., Gauthier S., Mérand Y., Bélanger A., Labrie C., Labrie F. Comparative effects of 28-day treatment with the new antiestrogen EM-800 and tamoxifen on estrogen-sensitive parameters in the intact mouse. Int. J. Cancer. 73:1997;381-391.
124. Luo S., Sourla A., Labrie C., Bélanger A., Labrie F. Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Endocrinology. 138:1997;4435-4444.
125. Luo S., Stojanovic M., Labrie C., Labrie F. Inhibitory effect of the novel antiestrogen EM-800 and medroxyprogesterone acetate (MPA) on estrone-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Int. J. Cancer. 73:1998;580-586.
126. Jordan V.C. Antitumour activity of the antiestrogen ICI 46,474 (tamoxifen) in the dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinoma model (Abstr. 243). J. Steroid Biochem. 5:1974;354.
127. Jordan V.C. Effect of tamoxifen (ICI 46,474) on initiation and growth of DMBA-induced rat mammary carcinoma. Eur. J. Cancer. 12:1976;419-424.
128. Kawamura I., Mizota T., Kondo N., Shimomura K., Kohsaka M. Antitumor effects of droloxifene, a new antiestrogen drug, against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats. Jpn J. Pharmac. 57:1991;215-224.
129. Fendl K.C., Zimniski S.J. Role of tamoxifen in the induction of hormone-independent rat mammary tumors. Cancer Res. 52:1992;235-237.
130. Jordan V.C. Use of the DMBA-induced rat mammary carcinoma system for the evaluation of Tamoxifen as a potential adjuvant therapy. Rev. Endocr. Relat. Cancer. Suppl:1978;49-55.
131. Poulin R., Baker D., Labrie F. Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line. Breast Cancer Res. Treat. 12:1988;213-225.
132. 5-steroids in the ZR-75-1 human breast cancer cell line. Cancer Res. 46:1986;4933-4937.
133. Dauvois S., Li S., Martel C., Labrie F. Inhibitory effect of androgens on DMBA-induced mammary carcinoma in the rat. Breast Cancer Res. Treat. 14:1989;299-306.
134. Li S., Martel C., Dauvois S., Bélanger A., Labrie F. Effect of estrone on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat: a model of post-menopausal breast cancer. Endocrinology. 134:1994;1352-1357.
135. Valavaara R. Phase II trials with Toremifene in advanced breast cancer: a review. Breast Cancer Res. Treat. 16:(Suppl.):1990;S31-S35.
136. Loser R., Seibel K., Roos W., Eppenberger U. In vivo and in vitro antiestrogenic action of 3-hydroxytamoxifen, tamoxifen and 4-hydroxytamoxifen. Eur. J. Cancer Clin. Oncol. 21:1985;985-990.
137. DeFriend D.J., Anderson E., Bell J., Wilks D.P., West C.M., Mansel R.E., Howell A. Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro. Br. J. Cancer. 70:1994;204-211.
138. Gottardis M.M., Jordan V.C. Development of tamoxifen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res. 48:1988;5183-5187.
139. Howell A., DeFriend D., Robertson J., Blamey R., Walton P. Response to a specific antiestrogen (ICI 182780) in tamoxifen-resistant breast cancer. Lancet. 345:1995;29-30.
140. Osborne C.K., Coronado Heinsohn E.B., Hilsenbeck S.G., McCue B.L., Wakeling A.E., McClelland R.A., Manning D.L., Nicholson R.I. Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. J. Natl Cancer Inst. 87:1995;746-750.
141. Lykkesfeldt A.E., Sorensen E.K. Effect of estrogens and antiestrogens on cell proliferation and synthesis of secreted proteins in the human breast cancer cell line MCF-7 and tamoxifen resistant variant subline. AL 1. Acta Oncol. 31:1992;131-138.
142. Pritchard K.I., Thomson D.B., Myers R.E., Sutherland D.J., Mobbs B.G., Meakin J.W. Tamoxifen therapy in premenopausal patients with metastatic breast cancer. Cancer. Treat. Rep. 64:1980;787-796.
143. Hoogstraten B., el Mawla Gad N., Maloney T.R., Fletcher W.S., Vaughn C.B., Tranum B.L., Athens J.W., Costanzi J.J., Foulkes M. Combined modality therapy for first recurrence of breast cancer. A Southwest Oncology Group study. Cancer. 54:1984;2248-2256.
144. Wiebe V.J., Osborne C.K., Fuqua S.A., DeGregorio M.W. Tamoxifen resistance in breast cancer. Crit. Rev. Oncol. Hematol. 14:1993;88-173.
145. Brunner N., Frandsen T.L., Holst-Hansen C., Bei M., Thompson E.W., Wakeling A.E., Lippman M.E., Clarke R. MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780. Cancer Res. 53:1993;3229-3232.
146. Lykkesfeldt A.E., Madsen M.W., Briand P. Altered expression of estrogen-regulated genes in a tamoxifen-resistant and ICI 164,384 and ICI 182,780 sensitive human breast cancer cell line, MCF-7/TAMR-1. Cancer. Res. 54:1994;1587-1595.
147. Coopman P., Garcia M., Brunner N., Derocq D., Clarke R., Rochefort H. Anti-proliferative and anti-estrogenic effects of ICI 164,384 and ICI 182,780 in 4-OH-tamoxifen-resistant human breast-cancer cells. Int. J. Cancer. 56:1994;295-300.
148. Gottardis M.M., Jiang S.Y., Jeng M.H., Jordan V.C. Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Res. 49:1989;4090-4093.
149. Osborne C.K., Coronado E.B., Allred D.C., Wiebe V., DeGregorio M. Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. J. Natl Cancer Inst. 83:1991;1477-1482.
150. Osborne C.K., Jarman M., McCague R., Coronado E.B., Hilsenbeck S.G., Wakeling A.E. The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. Cancer Chemother. Pharmac. 34:1994;89-95.
151. Osborne C.K., Coronado E.B., Robinson J.P. Human breast cancer in the athymic nude mouse: cytostatic effects of long-term antiestrogen therapy. Eur. J. Cancer Clin. Oncol. 23:1987;1189-1196.
152. Osborne C.K., Wiebe V.J., McGuire W.L., Ciocca D.R., DeGregorio M.W. Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients. J. Clin. Oncol. 10:1992;304-310.
153. Osborne C.K., von Hoff D.D., Mullins K. Endocrine therapy testing of human breast cancers in the soft agar clonogenic assay. Breast Cancer Res. Treat. 6:1985;229-235.
154. Nomura Y., Tashiro H., Hisamatsu K. Differential effects of estrogen and antiestrogen on in vitro clonogenic growth of human breast cancers in soft agar. J. Natl Cancer Inst. 82:1990;1146-1149.
155. Wakeling A.E. Comparative studies on the effects of steroidal and nonsteroidal oestrogen antagonists on the proliferation of human breast cancer cells. J. Steroid Biochem. 34:1989;183-188.
156. Berthois Y., Katzenellenbogen J.A., Katzenellenbogen B.S. Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc. Natl Acad. Sci., USA. 83:1986;2496-2500.
157. Cormier E.M., Jordan V.C. Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor. Eur. J. Cancer Clin. Oncol. 25:1989;57-63.
158. Plotkin D., Lechner J.J., Jung W.E., Rosen P.J. Tamoxifen flare in advanced breast cancer. JAMA. 240:1978;2644-2646.
159. McIntosh I.H., Thynne G.S. Tumor stimulation by anti-oestrogens. Br. J. Surg. 64:1977;900-901.
160. Clarysse A. Hormone-induced tumor-flare. Eur. J. Cancer Clin. Oncol. 21:1985;545-547.
161. T.J. Powles, Efficacy of tamoxifen as treatment of breast cancer. Semin. Oncol 24 (Suppl. 1) (1997) S1-48-S1-54.
162. Jones C.D., Jevnikar M.G., Pike A.J., Peters M.K., Black L.J., Thompson A.R., Falcone J.F., Clemens J.A. Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity. J. Med. Chem. 27:1984;1057-1066.
163. Yang N.N., Venugopalan M., Hardikar S., Glasebrook A. Identification of an estrogen response element activated by metabolites of 17β-estradiol and raloxifene. Science. 273:1996;1222-1225.
164. 5 adrenal steroids. Endocrinology. 127:1990;2757-2762.
165. B. MacMahon, Overview of studies on endometrial cancer and other types of cancer in humans: perspectives of an epidemiologist, Semin. Oncol 24 (Suppl. 1) (1997) S1-122-S1-139.
166. R.W. Carlson, Overview from a medical oncologist. Semin. Oncol 24 (Suppl. 1) (1997) S1-151-S1-157.
167. Satyaswaroop P.G., Zaino R.J., Mortel R. Estrogen-like effects of Tamoxifen on human endometrial carcinoma transplanted into nude mice. Cancer Res. 44:1984;4006-4010.
168. Clarke C.L., Satyaswaroop P.G. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma. Cancer Res. 45:1985;5417-5420.
169. Anzai Y., Holinka C.F., Kuramoto H., Gurpide E. Stimulatory effects of 4-hydroxytamoxifen on proliferation of human endometrial adenocarcinoma cells (Ishikawa line). Cancer Res. 49:1989;2362-2365.
170. Croxtall J.D., Elder M.G., White J.O. Hormonal control of proliferation in the Ishikawa endometrial adenocarcinoma cell line. J. Steroid Biochem. 35:1990;665-669.
171. Jamil A., Croxtall J.D., White J.O. The effect of anti-oestrogens on cell growth and progesterone receptor concentration in human endometrial cancer cells (Ishikawa). J. Molec. Endocr. 6:1991;215-221.
172. Smith D.C., Prentice R., Thompson D.J., Herrmann W.L. Association of exogenous estrogen and endometrial carcinoma. N. Engl. J. Med. 293:1975;1164-1167.
173. Ziel H.K., Finkle W.D. Increased risk of endometrial carcinoma among users of conjugated estrogens. N. Engl. J. Med. 293:1975;1167-1170.
174. Hoover R., Fraumeni J.F., Everson R., Myers M.H. Cancer of the uterine corpus after hormonal treatment for breast cancer. Lancet. 1:1976;885-887.
175. Harper M.J., Walpole A.L. Contrasting endocrine activities of cis and trans isomers in a series of substituted triphenylethylenes. Nature. 212:1966;87.
176. Harper M.J., Walpole A.L. A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J. Reprod. Fertil. 13:1967;101-119.
177. Riggs B.L. Overview of osteoporosis. West J. Med. 154:1991;63-77.
178. Stevenson J.C., Lees B., Devenport M., Cust M.P., Ganger K.F. Determinants of bone density in normal women: risk factors for future osteoporosis? Br. Med. J. 298:1989;924-928.
179. Matthews K.A., Meilahn E., Kuller L.H., Kelsey S.F., Caggiula A.W., Wing R.R. Menopause and risk factors for coronary heart disease. N. Engl. J. Med. 321:1989;641-646.
180. Gordon T., Kannel W.B., Hjortland M.C., McNamara P.M. Menopause and coronary heart disease: The Framingham Study. Ann. Int. Med. 89:1978;157-161.
181. Cummings S.R. Evaluating the benefits and risks of postmenopausal hormonal therapy. Am. J. Med. 91:(Suppl. 5B):1991;14S-18S.
182. Cust M.P., Gangar K.F., Whitehead M.I. Oestrogens and cancer. Drife J.O., Studd J.W.W. HRT and Osteoporosis. 1990;177-195 Springer-Verlag, London.
183. Judd H.L., Meldrum D.R., Deftos L.J., Henderson B.E. Estrogen replacement: Indications and complications. Ann. Int. Med. 98:1983;195-205.
184. Hunt K., Vessey M., McPherson K., Coleman M. Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. Br. J. Obstet. Gynecol. 94:1987;620-635.
185. Colditz G.A., Hankinson S.E., Hunter D.J., Willett W.C., Manson J.E., Stampfer M.J., Hennekens C., Rosner B., Speizer F.E. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N. Engl. J. Med. 332:1995;1589-1593.
186. Love R.R., Wiebe D.A., Newcomb P.A., Cameron L., Leventhal H., Jordan V.C., Feyzi J., DeMets D.L. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann. Intern. Med. 115:1991;860-864.
187. Love R.R., Mazees R.B., Barden H.S., Epstein S., Newcomb P.A., Jordan V.C., Carbone P.P., DeMets D.L. Effects of Tamoxifen on bone mineral density in postmenopausal women with breast cancer. N. Engl. J. Med. 326:1992;852-856.
188. Martel C., Sourla A., Pelletier G., Labrie C., Fournier M., Picard S., Li S., Stojanovic M., Labrie F. Predominant androgenic component in the stimulatory effect of dehydroepiandrosterone on bone mineral density in the rat. J. Endocr. 157:1998;433-442.
189. Black L.J., Sato M., Bowley E.R., Magee D.E., Bekele A., Williams D.C., Cullinan G.J., Bendele R., Kaufman R.F., Bensch W.R., Frolik C.A., Termine J.D., Bryant H.U. Raloxifene (LY139481 HCl) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J. Clin. Invest. 93:1994;63-69.
190. Lundeen S.G., Carver J.M., McKeen M.L., Winneker R.C. Characterization of the ovariectomized rat model for the evaluation of estrogen effects on plasma cholesterol levels. Endocrinology. 138:1997;1552-1558.
191. Grese T.A., Sluka J.P., Bryant H.U., Cole H.W., Kim J.R., Magee D.E., Rowley E.R., Sato M. Benzopyran selective estrogen receptor modulators (serms): pharmacological effects and structural correlation with raloxifen. Bioorg. Med. Chem. 6:1996;903-908.
192. Draper M.W., Flowers D.E., Neild J.A., Huster W.J., Zerbe R.L. Antiestrogenic properties of raloxifene. Pharmacology. 50:1995;209-217.
193. Kauffman R.F., Bryant H.U. Effective therapeutic management of the postmenopausal state will be a cornerstone in strategies for preserving or improving women's health in the 21st century. Drug News and Perspectives. 8:1995;531-539.
194. Ettinger B., Genant H.K., Cann C.E. Long-term estrogen replacement therapy prevents bone loss and fractures. Ann. Intern. Med. 102:1985;319-324.
195. Field C.S., Ory S.J., Wahner H.W., Herrmann R.R., Judd H.L., Riggs B.L. Preventive effects of transdermal 17 beta estradiol on osteoporotic changes after surgical menopause: a two year placebo controlled trial. Am. J. Obstet. Gynecol. 168:1993;114-121.
196. Weiss N.S., Ure C.L., Ballard J.H., Williams A.R., Daling J.R. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N. Engl. J. Med. 303:1980;1195-1198.
197. Lufkin E.G., Wahner H.W., WM O.F., Hodgson S.F., Kotowicz M.A., Lane A.W., Judd H.L., Caplan R.H., Riggs B.L. Treatment of postmenopausal osteoporosis with transdermal estrogen [see comments]. Ann. Intern. Med. 117:1992;1-9.
198. Dipippo V.A., Lindsay R., Powers C.A. Estradiol and tamoxifen interactions with thyroid hormone in the ovariectomized-thyroidectomized rat. Endocrinology. 136:1995;1020-1033.
199. Ke H.Z., Simmons H.A., Pirie C.M., Crawford T.D., Thompson D.D. Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats. Endocrinology. 136:1995;2435-2441.
200. Russell J.C., Amy R.M., Graham S., Wenzel L.M., Dolphin P.J. Effects of castration on hyperlipidemic, insulin resistant JCR:LA-corpulent rats. Atherosclerosis. 100:1993;113-122.
201. Weinstein I., Wilcox H.G., Heimberg M. Effects of high-dose ethinyl estradiol on serum concentrations and hepatic secretion of the very-low density lipoprotein, triacylglycerol, cholesterol, and apolipoprotein A-I in the rat. Biochim. Biophys. Acta. 876:1986;450-459.
202. Windler E.E., Kovanen P.T., Chao Y.S., Brown M.S., Havel R.J., Goldstein J.L. The estradiol-stimulated lipoprotein receptor of rat liver. J. Biol. Chem. 255:1980;10464-10471.
203. Wilcox H.G., Kenagy R., Weinstein I., Heimberg M. Alterations of plasma HDL lipids and apolipoproteins in female rats treated with ethynyl estradiol. Biochim. Biophys. Acta. 666:1981;348-355.
204. Chao Y.S., Windler E.E., Chen G.C., Havel R.J. Hepatic catabolism of rat and human lipoproteins in rats treated with 17α-ethinyl estradiol. J. Biol. Chem. 254:1979;11360-11366.
205. Davis R.A., Roheim P.S. Pharmacologically induced hypolipidemia. The ethinyl estradiol-treated rat. Atherosclerosis. 30:1978;293-299.
206. Bruning P.F., Bonfrer J.M., Hart A.A., de Jong Bakkar M., Linders D., van Loon J., Nooyen W.J. Tamoxifen, serum lipoproteins and cardiovascular risk. Br. J. Cancer. 58:1988;497-499.
207. Love R.R., Newcomb P.A., Wiebe D.A., Surawicz T.S., Jordan V.C., Carbone P.P., DeMets D.L. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J. Natl Cancer Inst. 82:1990;1327-1332.
208. Walsh B.W., Schiff I., Rosner B., Greenberg L., Ravnikar V., Sacks F. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N. Engl. J. Med. 325:1991;1196-1204.
209. Barrett-Connor E. Estrogen and estrogen-progestogen replacement: therapy and cardiovascular diseases. Am. J. Med. 95:(Suppl. 5A):1993;40S-43S.
210. Staels B., Auwerx L., Chan L., von Tol A., Rosseneu M., Verhoeven G. Influence of development, estrogens, and food intake on apolipoprotein A-I, A-II and E mRNA in rat liver and intestine. J. Lipid Res. 30:1989;1137-1145.
211. Luo S., Sourla A., Gauthier S., Mérand Y., Labrie C., Bélanger A., Labrie F. Effect of 24-week treatment with the antiestrogen EM-800 on estrogen-sensitive parameters in intact and ovariectomized mice. Endocrinology. 139:1998;2645-2656.
212. Wakeling A.E., Bowler J. Novel antioestrogens without partial agonist activity. J. Steroid Biochem. 31:1988;645-653.
213. Nique F., Van de Velde P., Brémaud J., Hardy M., Philibert D., Teutsch G. 11β-amidoalkoxyphenyl estradiols, a new series of pure antiestrogens. J. Steroid Biochem. Molec. Biol. 50:1994;21-29.
214. Favoni R.E., de Cupis A. Steroidal and nonsteroidal oestrogen antagonists in breast cancer: basic and clinical appraisal. Trends Pharmac. Sci. 19:1998;406-415.
215. Nicholson R.I., Gee J.M.W., Francis A.B., Manning D.L., Wakeling A.E., Katzenellenbogen B.S. Observations arising from the use of pure antioestrogens on oestrogen-responsive (MCF-7) and oestrogen growth-independent (K3) human breast cancer cells. Endocrine-Related Cancer. 2:1995;115-121.
216. Pavlik E.J., Nelson K., Srinivasan S., Powell D.E., Kenady D.E., DePriest P.D., Gallion H.H., van Nagell J.R. Jr. Resistance to tamoxifen with persisting sensitivity to estrogen: possible mediation by excessive antiestrogen binding site activity. Cancer. Res. 52:1992;4106-4112.
217. Encarnacion C.A., Ciocca D.R., McGuire W.L., Clark G.M., Fuqua S.A., Osborne C.K. Measurement of steroid hormone receptors in breast cancer patients on tamoxifen. Breast Cancer Res. Treat. 26:1993;237-246.
218. Buzdar A.U., Marcus C., Holmes F., Hug V., Hortobagyi G. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology. 45:1988;344-345.
219. Vancutsem P.M., Lazarus P., Williams G.M. Frequent and specific mutations of the rat p53 gene in hepatocarcinomas induced by Tamoxifen. Cancer Res. 54:1994;3864-3867.
220. Moyer D.L., de Lignières D., Drigues P., Pez J.P. Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. Fertil. Steril. 59:1993;992-997.
221. Sourla A., Luo S., Labrie C., Bélanger A., Labrie F. Morphological changes induced by six-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800. Endocrinology. 138:1997;5605-5617.
222. Luo S., Labrie C., Labrie F. Prevention of development of dimenthylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat by the new nonsteroidal antiestrogen EM-800 (SCH 57050). Breast Cancer Res. Treat. 49:1998;1-11.
223. Cheng Y., Prusoff W.H. Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I50) on an enzymatic reaction. Biochem. Pharmac. 22:1973;3099-3108.
224. Martel C., Provencher L., Li X., St-Pierre A., Leblanc G., Gauthier S., Mérand Y., Labrie F. Binding characteristics of novel nonsteroidal antiestrogens to the rat uterine estrogen receptors. J. Steroid Biochem. Molec. Biol. 64:1998;199-205.