Abstract:
: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.
journal_name
Steroidsjournal_title
Steroidsauthors
Jordan VC,Brodie AMdoi
10.1016/j.steroids.2006.10.009subject
Has Abstractpub_date
2007-01-01 00:00:00pages
7-25issue
1eissn
0039-128Xissn
1878-5867pii
S0039-128X(06)00220-0journal_volume
72pub_type
杂志文章,评审相关文献
STEROIDS文献大全abstract::Glucocorticoids (GCs) are widely prescribed as adjuvant therapy for breast cancer patients. Unlike other steroid hormone receptors, the GC receptor is not considered an oncogene. Research in the past few years has revealed the complexity of GC-mediated signaling, but it remains puzzling whether GCs promote or inhibit ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2020.108738
更新日期:2020-12-01 00:00:00
abstract::3 beta-Hydroxy-5-androsten-17-one is converted to 5-androstene-3, 17-dione by rat liver alcohol dehydrogenase (ADH). We have reported on the purity of the enzyme which is eluted with pyrazole as a single homogeneous protein using an AMP-agarose affinity column. Rat liver ADH can oxidize hydroxyl groups not only at 3 b...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(82)90079-4
更新日期:1982-11-01 00:00:00
abstract::This study was designed to describe the time-course changes of catabolic proteins following muscle atrophy induced by 10 days of dexamethasone (DEX). Rats underwent DEX treatment for 1, 3, 5, 7 and 10 days. Body weight (BW) and lean mass were obtained using a dual energy X-ray absorptiometry (DEXA) scan. Muscle ringer...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2015.12.016
更新日期:2016-03-01 00:00:00
abstract::The present study was undertaken to examine the mechanism whereby beta-lipotropin stimulates adrenal steroidogenesis. In guinea pig adrenal cells, beta-lipotropin (10(-8) M) increased basal steroid production 6-, 4-, and 5-fold for cortisol, androstenedione, and dehydroepiandrosterone (DHEA), respectively, whereas the...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(96)00002-5
更新日期:1996-05-01 00:00:00
abstract::During our studies of the hepatic androgen receptor in cynomolgus monkeys, tritiated mibolerone +/- a 200-fold excess of unlabeled mibolerone has been used to determine specific binding in cytosol. During time-course studies, high-capacity, unsaturable binding of [3H]mibolerone was noted after short-term incubations (...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(95)00116-8
更新日期:1995-11-01 00:00:00
abstract::Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(79)80017-3
更新日期:1979-11-01 00:00:00
abstract::20-Hydroxyecdysterone - (2β,3β,5β,22R)-2,3,14,20,22,25-hexahydroxycholest-7-en-6-one was isolated in satisfactory yield using ethanol extraction from the aerial part of Silene wolgensis (Hornem.) Otth; sometimes Silene wolgensis (Willd.) Bess. ex Spreng. The complexation of the phytoecdysteroid with β-cyclodextrin was...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2018.11.007
更新日期:2019-07-01 00:00:00
abstract::Contraceptive methods for breastfeeding women should be safe for the mother and infant and should not interfere with lactation. Progestin-only methods meet these conditions and can be used from the sixth week postpartum. Because all progestins are excreted in milk, those that are insufficiently active by the oral rout...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00125-2
更新日期:2000-10-01 00:00:00
abstract::The 21-hydroxy analogues of 11,19-oxidoprogesterone and 6,19-oxidoprogesterone have been synthesized from readily available materials. Hydroxylation at C-21 was effected with iodosobenzene (from phenyliodosodiacetate and methanolic potassium hydroxide) on a 20-ketopregnane. For the 11,19-oxido derivative, the hydroxyl...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(94)00052-e
更新日期:1995-03-01 00:00:00
abstract::Osteoblasts are a main target for the steroid 1alpha,25(OH)2-Vitamin D3 (1,25D3), where a major outcome is the modulation of the bone remodeling process. 1,25D3 deficiency leads to clinical disorders such as osteomalacia and osteoporosis, characterized by a state of insufficiently calcified tissue and bone loss, respe...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2004.05.003
更新日期:2004-08-01 00:00:00
abstract::The leaky heme mutants G204, G216, and G214 are shown to accumulate exogenous sterols. Unlike hem mutants which have complete blocks in the heme pathway, these strains do not require ergosterol, methionine, or unsaturated fatty acids for growth. The addition of aminolevulinic acid to the growth medium inhibited sterol...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(89)90035-4
更新日期:1989-03-01 00:00:00
abstract::The structure of dehydro-oogoniol (3 beta,11 alpha,15 beta,29-tetrahydroxystigmasta-5,24(28)(E)-dien-7-one), a female-activating hormone of the water mold Achlya, has been confirmed by synthesis. The starting material was progesterone, which was converted to the 11 alpha, 15 beta-dihydroxy derivative by microbiologica...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(89)90019-6
更新日期:1989-03-01 00:00:00
abstract::11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the enzyme that catalyzes the conversion of biologically active glucocorticoids to their inactive metabolites, was shown to be located exclusively in Leydig cells of the rat testis, and its appearance was associated with the developmental rise in testosterone. Thus, ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(96)00225-5
更新日期:1997-03-01 00:00:00
abstract::Contrary to the long-held postulate of steroid-hormone binding globulin action, these protein carriers of steroids are major players in steroid actions in the body. This manuscript will focus on our work with sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) and demonstrate how they are act...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2013.11.010
更新日期:2014-03-01 00:00:00
abstract::The biotransformation of a series of delta 4-3-ketosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the 5 alpha-dihydrosteroid was observed for several substrates of the androstene and pregnene series: the reaction is tolerant of non-polar substituents (Cl and CH3) at C-4 of...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(94)90020-5
更新日期:1994-11-01 00:00:00
abstract::Estradiol (E2), progesterone (P4), and oxytocin (OT) are important for the initiation of luteolysis in ruminants but the mechanisms involved are still poorly understood. The objective of this study was to determine if duration of exposure of bovine endometrial epithelial cells to P4 affected the response of the cells ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(03)00094-1
更新日期:2003-09-01 00:00:00
abstract::2-Phenyl-6-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran (II) is converted into racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol (VIII). ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(79)90023-0
更新日期:1979-02-01 00:00:00
abstract::Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of cholesterol biosynthesis, which is catalyzed by 7-dehydrocholesterol reductase (DHCR7). The disorder exhibits several phenotypic traits including dysmorphia and mental retardation with a broad range of severity. Pathogenesis of SLOS is c...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.07.002
更新日期:2007-10-01 00:00:00
abstract::Three new pregnane steroids, 2beta,3beta,5beta-trihydroxy-pregn-20-en-6-one (1), 3beta-hydroxy-5alpha-pregn-7,20-dien-6-one (2), and 3beta-acetoxy-5alpha-pregn-7,20-dien-6-one (3) were isolated from the twigs and leaves of Turraea pubescens, and were structurally elucidated on the basis of spectroscopic data and chemi...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2006.04.010
更新日期:2006-08-01 00:00:00
abstract::The apolar ecdysteroid present in the developing embryo of the blue crab, Callinectes sapidus Rathbun, is tentatively identified as ponasterone A (2 beta, 14 alpha, 20,22-pentahydroxy-5, beta-cholest-7-en-6-one) on the basis of chromatographic, immunological, and mass spectral evidence. The apolar ecdysteroid present ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(79)90092-8
更新日期:1979-12-01 00:00:00
abstract::Two isomeric dimeric steroids, 3,3'-bis(methyl 3-hydroxyandrost-4-en-17-on-19-oate-3-yl), with symmetrical (alpha, alpha') and unsymmetrical structures (alpha,beta'), have been obtained by reduction of methyl androst-4-ene-3,17-dion-19-oate with zinc in aqueous acetic acid together with the major products, the isomeri...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(99)00108-7
更新日期:2000-04-01 00:00:00
abstract::Oleoyl-estrone (OE) induces a marked loss of body fat in rats by maintaining energy expenditure, body protein and blood glucose despite decreasing food intake. OE increases glucocorticoids, but they arrest OE lipid-mobilization. We studied here whether OE induces a direct effect on adrenal glands function as part of t...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2009.09.009
更新日期:2010-01-01 00:00:00
abstract::The role played by progestogens in modulating Schwann cell pathophysiology is well established. Progestogens exert their effects in these cells through both classical genomic and non-genomic mechanisms, the latter mediated by the GABA-A receptor. However, there is evidence that other receptors may be involved. Membran...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2017.09.009
更新日期:2019-02-01 00:00:00
abstract::Extranuclear estrogen receptors may mediate rapid effects of estradiol that communicate with nuclear receptors and contribute to proliferation of human cancers bearing these signaling proteins. To assess these growth-promoting pathways, we undertook controlled homogenization and fractionation of NIH-H23 non-small cell...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2005.02.017
更新日期:2005-05-01 00:00:00
abstract::Previous studies have demonstrated a persistent rise in serum cortisol concentrations after cardiac surgery. To further investigate this finding and to evaluate the effect of hemodilution that occurs with the onset of cardiopulmonary bypass (CPB), concentrations of cortisol-binding globulin (CBG), total and unbound co...
journal_title:Steroids
pub_type: 临床试验,杂志文章
doi:10.1016/s0039-128x(00)00133-1
更新日期:2000-09-01 00:00:00
abstract::Brassinosteroids (BRs) are an important class of plant hormones with a multitude of functions. They have been intensively investigated for their biosynthesis, distribution and physiological functions. The aim of this study was to examine possible effects of BRs on the plant plasma membrane cation conductances and Ca(2...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2014.10.008
更新日期:2015-05-01 00:00:00
abstract::A simplified, non-chromatographic method for aldosterone-gamma-lactone (2) radio-immunoassay is described, using a high titer aldosterone-gamma-lactone antibody. This method takes six working hours for completion; the blanks are below the sensitivity of the assay (0-10 pg), and the intra and interassay coefficient of ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(76)90004-0
更新日期:1976-11-01 00:00:00
abstract::The uterine milk (UTM) proteins are the major progesterone-regulated proteins secreted by the sheep uterus during pregnancy. Recently, proteins related to the UTM proteins have been identified in uterine secretions of the pregnant cow and sow. The present objective was to determine the time course for induction of the...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(91)90022-n
更新日期:1991-12-01 00:00:00
abstract::Fingernail clipping is expected to be a specimen for steroid testing, because it has several advantages over blood; i.e., noninvasive collection, ease of storage, portability and handling, and possibility for an assessment of the steroid status over a relatively long and retrospective time window. In this study, we ex...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2016.02.013
更新日期:2016-05-01 00:00:00
abstract::When day 6 rabbit blastocysts were cultured (3 embryos/mL) in medium 199 containing 3.68 microM estradiol-17 beta (E2), 40% of E2 was metabolized in 24 h, at a rate of 18 pmol/embryo(b)/h, yielding 4 major metabolite fractions. Two of them were identified to be estrogen glucosides: 17 beta-hydroxyestra-1,3,5(10)-trien...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(89)90053-6
更新日期:1989-10-01 00:00:00