Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer.


:This article describes the origins and evolution of "antiestrogenic" medicines for the treatment and prevention of breast cancer. Developing drugs that target the estrogen receptor (ER) either directly (tamoxifen) or indirectly (aromatase inhibitors) has improved the prognosis of breast cancer and significantly advanced healthcare. The development of the principles for treatment and the success of the concept, in practice, has become a model for molecular medicine and presaged the current testing of numerous targeted therapies for all forms of cancer. The translational research with tamoxifen to target the ER with the appropriate duration (5 years) of adjuvant therapy has contributed to the falling national death rates from breast cancer. Additionally, exploration of the endocrine pharmacology of tamoxifen and related nonsteroidal antiestrogen (e.g. keoxifene now known as raloxifene) resulted in the laboratory recognition of selective ER modulation and the translation of the concept to use raloxifene for the prevention of osteoporosis and breast cancer. However, the extensive evaluation of tamoxifen treatment revealed small but significant side effects such as endometrial cancer, blood clots and the development of acquired resistance. The solution was to develop drugs that targeted the aromatase enzyme specifically to prevent the conversion of androstenedione to estrone and subsequently estradiol. The successful translational research with the suicide inhibitor 4-hydroxyandrostenedione (known as formestane) pioneered the development of a range of oral aromatase inhibitors that are either suicide inhibitors (exemestane) or competitive inhibitors (letrozole and anastrozole) of the aromatase enzyme. Treatment with aromatase inhibitors is proving effective and is associated with reduction in the incidence of endometrial cancer and blood clots when compared with tamoxifen and there is also limited cross resistance so treatment can be sequential. Current clinical trials are addressing the value of aromatase inhibitors as chemopreventive agents for postmenopausal women.






Jordan VC,Brodie AM




Has Abstract


2007-01-01 00:00:00
















  • Endogenous oestrogens and breast cancer risk in premenopausal and postmenopausal women.

    abstract::Breast cancer risk is strongly related to several reproductive and hormonal factors, but the nature of the effects of endogenous oestrogens has been difficult to establish. Data are now available from several large prospective studies with biobanks of stored serum, enabling better characterization of the associations ...


    pub_type: 杂志文章


    authors: Key TJ

    更新日期:2011-07-01 00:00:00

  • Regulation of steroid production and its function within the corpus luteum.

    abstract::During the second half of the luteal phase, the human corpus luteum becomes responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate progesterone secretion tonically, and during this tonic stimulation, additional LH-independent progesterone pulses occur, which are particularly pronounced in wom...


    pub_type: 杂志文章,评审


    authors: Wuttke W,Theiling K,Hinney B,Pitzel L

    更新日期:1998-05-01 00:00:00

  • Marine sterols. VIII. Isolation and structure of sarcosterol, a new sterol with a delta17(20)-double bond from the soft coral Sarcophyton glaucum.

    abstract::The sterol mixture of the southern Japan's soft coral, Sarcophyton glaucum, was found to contain 11 sterols including a novel sterol, 23,24 xi-dimethylcholesta-5,22-dien-3 beta-ol and a new diunsaturated C29 sterol. 22,23-Dihydrobrassicasterol and gorgosterol were the major components in free- and esterified sterols r...


    pub_type: 杂志文章


    authors: Kobayashi M,Tomioka A,Mitsuhashi H

    更新日期:1979-09-01 00:00:00

  • Why do humans have two glucocorticoids: A question of intestinal fortitude.

    abstract::The main purpose of this review article is threefold (a) to try to address the question "why are two adrenal glucocorticoids, cortisol and corticosterone, secreted by humans and other mammalian species?", (b) to outline a hypothesis that under certain physiological conditions, corticosterone has additional biochemical...


    pub_type: 杂志文章,评审


    authors: Morris DJ

    更新日期:2015-10-01 00:00:00

  • Nine new steroidal glycosides from the roots of Cynanchum stauntonii.

    abstract::Nine new steroidal glycosides, named as stauntosides C-K (2, 5, 7-10, 13, 14, and 16), along with seven known compounds (1, 3, 4, 6, 11, 12, and 15) were isolated from the 95% ethanol extract of the roots of Cynanchum stauntonii. The structures of these new compounds were elucidated on the basis of extensive spectrosc...


    pub_type: 杂志文章


    authors: Yu JQ,Deng AJ,Qin HL

    更新日期:2013-01-01 00:00:00

  • Chemoselective reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by various hydride reagents.

    abstract::The chemoselectivity of rigid cyclic alpha,beta-unsaturated carbonyl group on the reducing agents was influenced by the ring size and steric factor. Cholesterol (cholest-5-en-3beta-ol) and dehydroepiandrosterone (DHEA) were oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form 1,4,6-cholestatrien-3-one and 1...


    pub_type: 杂志文章


    authors: Kim E,Ma E

    更新日期:2007-04-01 00:00:00

  • Sex shapes experimental ischemic brain injury.

    abstract::Biologic sex and sex steroids are important factors in clinical and experimental stroke. This review evaluates key evidence that biological sex strongly alters mechanisms and outcomes from cerebral ischemia. The role of androgens in male stroke is understudied and important to pursue given that male sex is a well know...


    pub_type: 杂志文章,评审


    authors: Cheng J,Hurn PD

    更新日期:2010-11-01 00:00:00

  • Measurement of bile acid synthesis by 14CO2: the metabolism of propionyl CoA.

    abstract::The relationship between 14CO2 evolution from the catabolism of [26 or 2714C] cholesterol to bile acids was studied in rats with biliary fistulae. When equal quantities of [26 or 2714C] cholesterol and [414C] cholesterol were administered, there was a significant linear relationship between 14CO2 expiration in the bre...


    pub_type: 杂志文章


    authors: Davis RA,Showalter P,Kern F Jr

    更新日期:1975-10-01 00:00:00

  • The role and mechanism of progesterone receptor activation of extra-nuclear signaling pathways in regulating gene transcription and cell cycle progression.

    abstract::Human progesterone receptor (PR) contains a polyproline motif in the amino-terminal domain that interacts with the SH3 domain of Src and mediates rapid activation of c-Src and downstream MAPK (Erk-1/-2) independent of the transcriptional activity of PR. Forcedly target PR to different locations in the cell by use of m...


    pub_type: 杂志文章,评审


    authors: Boonyaratanakornkit V,Bi Y,Rudd M,Edwards DP

    更新日期:2008-10-01 00:00:00

  • Progesterone and 17 alpha-OH-progesterone in concentrations similar to that of preovulatory follicular fluid is without effect on resumption of meiosis in mouse cumulus enclosed oocytes cultured in the presence of hypoxanthine.

    abstract::Some intermediates in the cholesterol biosynthesis between lanosterol and cholesterol are capable of inducing resumption of meiosis in cultured mouse oocytes without the presence of gonadotropins. The mechanism by which these so-called Meiosis Activating Sterols (MAS) activate the meiotic process is unknown, and it is...


    pub_type: 杂志文章


    authors: Yding Andersen C,Byskov AG

    更新日期:2002-11-01 00:00:00

  • Inhibition of progesterone synthesis in normal and transformed human placental cells by tight binding inhibitors of 3 beta-hydroxysteroid dehydrogenase.

    abstract::The biosynthesis of progesterone from [3H]pregnenolone was curvilinear over a 6 h time course in human placenta cytotrophoblasts and in human placenta choriocarcinoma cells (JEG-3 cells). Mass measurements determined independently by radioimmunoassay indicate that the progesterone synthesized by cytotrophoblasts (21.0...


    pub_type: 杂志文章


    authors: Sharp RB,Penning TM

    更新日期:1988-05-01 00:00:00

  • Synthesis of pentacyclic steroids.

    abstract::Due to their high profile biological activity, the steroids are among the most important secondary metabolites. A review of literature on the synthesis of pentacyclic steroids is presented. ...


    pub_type: 杂志文章,评审


    authors: Ibrahim-Ouali M

    更新日期:2008-09-01 00:00:00

  • Cortisol metabolism and excretion in the isolated perfused rat kidney.

    abstract::The isolated perfused rat kidney allows a simultaneous kinetic study of both the renal metabolism and the urinary excretion of cortisol and its metabolites in the rat. In this system, cortisol was completely metabolized within 120 minutes. The main renal metabolites of cortisol (cortisone, 20 reduced cortisol and 20 r...


    pub_type: 杂志文章


    authors: Reach G,Nakane H,Nakane Y,Auzan C,Corvol P

    更新日期:1977-11-01 00:00:00

  • A comparative study of enol aldehyde formation from betamethasone, dexamethasone, beclomethasone and related compounds under acidic and alkaline conditions.

    abstract::Enol aldehydes are one type of key degradation and metabolic intermediates from a group of corticosteroids containing the 1,3-dihydroxyacetone side chain on their D-rings, such as betamethasone, dexamethasone, beclomethasone, and related compounds. The formation of enol aldehydes from these corticosteroids is via acid...


    pub_type: 杂志文章


    authors: Chen B,Li M,Lin M,Tumambac G,Rustum A

    更新日期:2009-01-01 00:00:00

  • Novel action of estrone on vascular tissue: regulation of NOS and COX activity.

    abstract::The hypothesis tested in the present work is that estrone non-genomically regulates aortic nitric oxide synthase (NOS) and cyclooxygenase (COX) activities in female rats, and that such regulation depends on ovarian function. We found that physiological concentrations of estrone (E(1)) (0.1-10nM) significantly increase...


    pub_type: 杂志文章


    authors: Selles J,Polini N,Alvarez C,Massheimer V

    更新日期:2005-04-01 00:00:00

  • Relative mitogenic activities of various estrogens and antiestrogens.

    abstract::The abilities of a variety of estrogens and antiestrogens to stimulate DNA synthesis in the prepuberal rat uterus were compared. One microgram of each compound was administered in vivo via a single intraperitoneal injection. DNA synthesis was assayed in vitro in isolated nuclei 24 h later. The relative mitogenicities ...


    pub_type: 杂志文章


    authors: Stack G,Korach K,Gorski J

    更新日期:1989-08-01 00:00:00

  • Nodulisporisteriods A and B, the first 3,4-seco-4-methyl-progesteroids from Nodulisporium sp.

    abstract::Two new 4-methyl-progesteroids, nodulisporisteriod A (1) and nodulisporisteriod B (2), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1), along with two related metabolites, demethoxyviridin (3) and inoterpene B (4). Their structures were determined by detailed spectrosc...


    pub_type: 杂志文章


    authors: Zheng QC,Chen GD,Kong MZ,Li GQ,Cui JY,Li XX,Wu ZY,Guo LD,Cen YZ,Zheng YZ,Gao H

    更新日期:2013-09-01 00:00:00

  • Progestin metabolism in the rhesus monkey corpus luteum.

    abstract::For the purpose of describing the pathway by which estrones are synthesized in the rhesus monkey (Macaca mulatta) corpus luteum (CL), CL were obtained during the midluteal phase of the menstrual cycle and fragments incubated with equimolar amounts of [7-3H]pregnenolone plus [4-14C]progesterone. Metabolites including 3...


    pub_type: 杂志文章


    authors: Sholl SA,Wolf RC

    更新日期:1980-08-01 00:00:00

  • 1H NMR determination of adulteration of anabolic steroids in seized drugs.

    abstract::Counterfeiting and adulteration of pharmaceuticals is a prevalent problem worldwide and represents a major health risk to the population, with anabolic steroids being one of the main classes of drugs consumed and obtained from dubious sources. In this work, we propose the use of the 1H NMR technique to evaluate formul...


    pub_type: 杂志文章


    authors: Ribeiro MVM,Boralle N,Felippe LG,Pezza HR,Pezza L

    更新日期:2018-10-01 00:00:00

  • Sex steroid changes in porcine cystic ovarian disease.

    abstract::Ten sex steroids were measured in the peripheral serum and ovarian follicular fluid of female pigs with or without cystic ovarian disease. In general, progestin, especially progesterone, accumulated excessively in the fluid contained in cystic compared with normal follicles. Nonluteinized cystic follicles contained up...


    pub_type: 杂志文章


    authors: Babalola GO,Shapiro BH

    更新日期:1990-07-01 00:00:00

  • Hormone mediated changes in monoamine stores and regulation of enzymes of biosynthesis and metabolism in the rat adrenal gland. Influence of progesterone, estradiol, ACTH and testosterone administration.

    abstract::The influence of daily injections, for 7 days, of 17-hydroxyprogesterone caproate (8 mg/100 g body weight pro die), of estradiol-17 beta 17-undecylate (1.2 mg/100 g body weight pro die) of testosterone enanthate (2 mg/100 g body weight pro die) and of ACTH (4 IU/100 g body weight pro die) to male Wistar rats, weighing...


    pub_type: 杂志文章


    authors: Bukhari AR,Guessab A,Nicol ML

    更新日期:1981-07-01 00:00:00

  • 1H and 13C NMR characteristics of synthetic derivatives of steroid sapogenins. Part III. 16Beta,23:23,26-diepoxy side chains.

    abstract::The full assignments of the (1)H and (13)C NMR signals of steroids bearing the 16beta,23:23,26-diepoxy side chain are provided. Differentiation of the diasterotopic H-26 pair was achieved with the aid of NOESY experiments. The main substituent and steric effects associated with this moiety and their influence on the c...


    pub_type: 杂志文章


    authors: Vázquez-Ramírez I,Macías-Alonso M,Arcos-Ramos RO,Ruíz-Pérez KM,Solano-Ramírez DO,Iglesias Arteaga MA

    更新日期:2008-07-01 00:00:00

  • NFκB pathway is down-regulated by 1α,25(OH)(2)-vitamin D(3) in endothelial cells transformed by Kaposi sarcoma-associated herpes virus G protein coupled receptor.

    abstract::We have previously demonstrated that 1α,25 dihydroxy-vitamin D(3) (1α,25(OH)(2)D(3)) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)(2)D(3) exerts its growth i...


    pub_type: 杂志文章


    authors: Gonzalez-Pardo V,D'Elia N,Verstuyf A,Boland R,Russo de Boland A

    更新日期:2012-09-01 00:00:00

  • Aldosterone: the minority hormone of the adrenal cortex.

    abstract::In comparison with the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone is a minority hormone of the mammalian adrenal cortex, and its proper function is dependent upon protective physiological mechanisms. These include a particular site of aldosterone synthesis in zona glomerulosa cells ...


    pub_type: 杂志文章,评审


    authors: Müller J

    更新日期:1995-01-01 00:00:00

  • Differential binding of dexamethasone to ammonium sulfate precipitates of human adipose tissue cytosols.

    abstract::Saturation analysis of the binding of [3H]dexamethasone [( 3H]DEX) to ammonium sulfate precipitates (ASPs) confirmed the presence of a limited-capacity, high-affinity binder in human adipose tissue cytosols. Various non-radioactive steroids competed with [3H]DEX for binding to the ASPs in the following sequence: dexam...


    pub_type: 杂志文章


    authors: Miller LK,Kral JG,Strain GW,Zumoff B

    更新日期:1987-06-01 00:00:00

  • Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone.

    abstract::The potent antiproliferative effect of progestins has been utilized in clinical regimens for treatment of endometrial proliferative disorders. The progestin infiltrated intrauterine device used as therapy for endometrial carcinoma as well as endometrial hyperplasia yields a hundred-fold increase of local progestin con...


    pub_type: 杂志文章


    authors: Paulssen RH,Moe B,Grønaas H,Orbo A

    更新日期:2008-01-01 00:00:00

  • Androstenedione and testosterone biosynthesis by the adrenal cortex of the horse.

    abstract::An homogenate from cortical tissue of mare adrenals was incubated in the presence of tritiated pregnenolone. The (3H) androstenedione and the (3H) testosterone synthesized during the incubation were extracted, purified, and co-crystallized to constant specific activity in the presence of unlabeled carriers. The rate o...


    pub_type: 杂志文章


    authors: Silberzahn P,Rashed F,Zwain I,Leymarie P

    更新日期:1984-02-01 00:00:00

  • The effect of reduced oxygen tension on progesterone accumulation in rat granulosa cell cultures.

    abstract::Studies were carried out on the effect of oxygen tension on progesterone (P) accumulation in rat granulosa cell cultures. At 1-2% oxygen, basal, luteinizing hormone (LH)-stimulated, and follicle stimulating hormone (FSH)-stimulated P accumulations were 20, 18, and 11%, respectively, of P levels at 20% oxygen. Basal P ...


    pub_type: 杂志文章


    authors: Koos RD,Feiertag MA

    更新日期:1989-11-01 00:00:00

  • Serum asymmetric dimethylarginine, apelin, and tumor necrosis factor-α levels in non-obese women with polycystic ovary syndrome.

    abstract::Polycystic ovary syndrome (PCOS) is associated with multiple risk factors for cardiovascular disease (CVD), including insulin resistance, type 2 diabetes mellitus, obesity, hypertension, and dyslipidemia. In addition, hyperandrogenism may contribute to the pathogenesis of CVD, independent of obesity and insulin resist...


    pub_type: 杂志文章


    authors: Choi YS,Yang HI,Cho S,Jung JA,Jeon YE,Kim HY,Seo SK,Lee BS

    更新日期:2012-11-01 00:00:00

  • Preparation and characterization of (24R and 24S)-5beta-cholestane-3alpha,7alpha,24,25-tetrols and (24R and 24S)-5beta-cholestane-3alpha,24,25-triols.

    abstract::(24R and 24S)-5beta-cholestane-3alpha,7alpha,24,25-tetrols were prepared by osmium tetroxide oxidation of 5beta-cholest-24-ene-3alpha,7alpha-diol. The resulting diastereomeric tetrols were separated by thin-layer chromatography, their purity ascertained by melting point, gas-liquid chromatography and mass spectra and ...


    pub_type: 杂志文章


    authors: Batta AK,Dayal B,Tint GS,Shefer S,Toome V,Salen G,Mosbach EH

    更新日期:1978-01-01 00:00:00