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::These studies investigated whether treatment with carbenoxolone (CBX), an inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), resulted in an enhanced mineralocorticoid response to endogenous or infused cortisol. In conscious sodium replete sheep with a parotid fistula, infusion of CBX (40 mg/h for 10 days...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(97)00141-4
更新日期:1998-02-01 00:00:00
abstract::The crystal and molecular structure of 3-methoxy-9(10 leads to 19)abeo-1,3,5(10)-estratrien-17-one has been determined by X-ray analysis in order to ascertain the configuration at C(9). The seven-membered B-ring has a chair conformation and this causes the molecule to bow towards the alpha-face rather than towards the...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(76)90102-1
更新日期:1976-02-01 00:00:00
abstract::Several derivatives of the arthropod moulting hormone have been synthesized which were coupled to AH Sepharose 4B yielding about 2 mumole ligand per g wet gel. As an indication of the suitability of the ligands for biological work the puff inducing capacity of their methyl esters was tested. The methyl ester of inokos...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(76)90088-x
更新日期:1976-04-01 00:00:00
abstract::In this paper, we examine corticosteroid 11 beta-oxidation and 11-reduction as properties of the microsomal 11 beta-hydroxysteroid dehydrogenase complex in vertebrate livers. No hepatic activity in the oxidative direction (11 beta -dehydrogenase) was found in the frog, toad, mud puppy, shark, and bird livers. In contr...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(88)90118-3
更新日期:1988-11-01 00:00:00
abstract::Aldosterone induces fibrotic changes in cardiovascular tissues but its effects have usually been demonstrated in models of pre-existing renal injury and/or hypertension. This study tests the hypothesis that aldosterone can directly induce vascular fibrotic changes in the absence of prior renal injury or hypertension. ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.12.007
更新日期:2013-03-01 00:00:00
abstract::A novel steroid, 1alpha,3beta,5beta-trihydroxy-24-methylenecholestan-6-one (gibberoketosterol) (1), along with four known steroids, was isolated from the lipophilic extracts of a Taiwanese soft coral Sinularia gibberosa. The structure of the new metabolite was determined on the basis of extensive spectral analyses and...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(03)00036-9
更新日期:2003-04-01 00:00:00
abstract::Morphologic changes at the interface of rat endometrial luminal epithelial cells and the stromal cells immediately adjacent were examined and correlated with hypertrophy of the epithelial cells during estradiol (E2) infusion (1 microgram E2/24 h). While the lamina densa in castrate endometrium was thread-like, it beca...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(91)90061-y
更新日期:1991-03-01 00:00:00
abstract::The incorporation of the heterocycles into the steroid nucleus has been recognized as a useful strategy to develop new steroidal agents for disease treatment. Representative examples are abiraterone and galeterone, which are presently used in clinic for the treatment of advanced prostate cancers. Herein we have develo...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2019.108465
更新日期:2019-11-01 00:00:00
abstract::Based on histological criteria, Kingsley and Bogdanove (3) reported that the benzoate ester of 17beta-hydroxy-5alpha-androstan-3-one (5alpha-DHT), unlike testosterone propionate, is unable to induce vaginal mucification when given subcutaneously to rats. In contrats, Kennedy (4) found in estrogen-pretreated rats that ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(76)90061-1
更新日期:1976-03-01 00:00:00
abstract::11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), by converting cortisol and corticosterone to hormonally inactive cortisone and 11-dehydrocorticosterone, respectively, is an important pre-receptor signaling pathway for the renal mineralocorticoid receptor (MR). This receptor has an equal affinity for the glucocorti...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(94)00024-7
更新日期:1995-01-01 00:00:00
abstract::The catalytic cycloalumination of 2'-methylidene-2',3'-ethano-(5α)-cholestane with Et3Al catalyzed by Cp2ZrCl2 was performed for the first time to give spiro[2',3'-ethano-(5α)-cholestane-2',3″-aluminacyclopentane] in a ~75% yield and with high stereoselectivity (>98%). The obtained cyclic organoaluminum compound was t...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2013.09.007
更新日期:2013-12-11 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::Rat uterine luminal epithelial cells (LEC) responded differently when exposed to an injection of 1.0 microgram estradiol-17 beta (E2) compared to a continuous infusion of E2 at the rate of 1.0 microgram/24 hours. After injection or beginning infusion, LEC mean nuclear area significantly decreased by 4 h, then increase...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(85)90017-0
更新日期:1985-06-01 00:00:00
abstract::The preparation of 9alpha, 11xi-tritiated 17alpha-ethinyl estradiol, mestranol, estradiol-17beta, and norethindrone are described. Estrone-3-methyl ether was employed as starting material, and ethinylation with lithium acetylide-ethylene diamine resulted in 95% mestranol. Demethylation of mestranol with boron tribro...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(71)90028-6
更新日期:1971-08-01 00:00:00
abstract::Radioactive mestranol (ME) and/or ethynylestradiol (EE) were administered to women in Nigeria, Sri Lanka, and the USA, and the types and patterns of radioactive urinary conjugates examined by Sephadex LH-20 chromatography. There are no differences in the total excretion of urinary radioactivity over 3 days. Consistent...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(80)90001-x
更新日期:1980-09-01 00:00:00
abstract::A novel synthetic route of producing ursodeoxycholic acid (UDCA) was developed through multiple reactions from cheap and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, bases and reaction temperatures of the route were investigated and optimized. In the straightforward route...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2020.108600
更新日期:2020-05-01 00:00:00
abstract::A mechanistic study on the nucleophilic substitution of a strictly geometric 21-bromo-3alpha-hydroxyl-3beta-methoxymethyl-5alpha-pregnan-20-one was described. Reaction of the alpha-bromoketone with excess lithium imidazole followed by the addition of extra bases including n-butyllithium, methyllithium, lithium piperid...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2006.07.004
更新日期:2006-11-01 00:00:00
abstract::Desoxymethyltestosterone (DMT; 17β-hydroxy-17α-methyl-5α-androst-2-ene) is a designer steroid present in hormonal supplements distributed illegally as such or in combination with other steroids, for self-administration. It figures on the list of substances prohibited in sports and its detection in athlete's urine samp...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.02.008
更新日期:2012-05-01 00:00:00
abstract::[7beta-3H]-(24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and [7beta-3H]-27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid (C27 and C26 bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(78)90076-4
更新日期:1978-12-01 00:00:00
abstract::The ability of human adult adrenal to utilize progesterone (P4) for cortisol (F) synthesis in vitro has been compared with that of fetal adrenal tissue. Explant cultures were studied for 6 days using Ham's F10 medium supplemented with 10% fetal bovine serum (FBS), with or without added P4 as substrate. Short-term (4h)...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(86)90097-8
更新日期:1986-04-01 00:00:00
abstract::The synthesis of (22E,24R)-5 alpha-ergosta-2,22-dien-6-one (2), a key intermediate to the preparation of 24-epibrassinolide (1), was achieved through the 3,6-diketone 8 in a 40% overall yield in five steps starting from ergosterol (3). ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(96)00087-6
更新日期:1996-09-01 00:00:00
abstract::A short and efficient synthesis of steroid synthons, di(tert-butyldimethylsilyl) ethers of 3,21-dihydroxy-24-nor-chol-5-en-23-al (8 and 10) and of ethyl 3,21-dihydroxy-25-homo-chola-5,23-dien-25-oate (9 and 11), having natural (20R) and unnatural (20S) configuration from 3β-(tert-butyldimethylsilyloxy)-14α,20ξ-card-5-...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2011.01.010
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in sept...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.06.001
更新日期:2012-09-01 00:00:00
abstract::The conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT) has been demonstrated in Penicillium crustosum broth obtained from fermented pistachios, lemons and corn tortillas. Furthermore, the presence of 5alpha-reductase enzyme, which is responsible for this conversion, has been established by electrophore...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(02)00180-0
更新日期:2003-03-01 00:00:00
abstract::A heretofore unknown metabolite of vitamin D3 was isolated from the 1 alpha, 24, 25-trihydroxyvitamin D3 fraction of lipid extracts obtained from plasma of rats which were given intravenous or oral doses of 100 pmol/100 g of either 1 alpha-hydroxyvitamin D3 or 1 alpha, 23-dihydroxyvitamin D3. Doses of 25-250 pmoles of...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(80)90065-3
更新日期:1980-07-01 00:00:00
abstract::By analyzing the steroidal content of fresh whole plants of Tacca subflabellata (Taccaceae), we isolated one sapogenin and eight glycosides with four kinds of steroidal skeletons including four new glycosides, named taccasubosides A-D (1-4), together with five known compounds. Among them, compound 1 is the first penta...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2011.04.003
更新日期:2011-09-01 00:00:00
abstract::We describe a convenient and stereoselective route to the synthesis of 27-hydroxycholesterol. Also its radiolabeled analog, 22, 23 di [(3)H]-27-hydroxycholesterol with high specific radioactivity (55 Ci/mmol) was synthesized by this method. Julia condensation of steroidal 22-sulfone with aldehyde, led to the addition ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00099-4
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Estrogen replacement therapy increases risk for ovarian epithelial cancer, a cancer of mainly older women, yet the response of older ovarian surface epithelium (OSE) to repeat estrogen exposure overtime has not been studied. We have previously reported significant reductions in estrogen receptor (ER) protein...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.02.015
更新日期:2012-05-01 00:00:00
abstract::We have previously shown that the photoactive 4-azasteroid, [1,2 3H]N-4(benzylbenzoyl)-3-oxo-4-aza-4-methyl-5alpha-androst an-17beta-carboxamide is an effective probe of rat steroid 5alpha-reductase (isozyme-1) (5alphaR-1). In the current investigation, PEG-fractionated (6.5%) detergent-solubilized preparations contai...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(98)00087-7
更新日期:1999-03-01 00:00:00
abstract::Two new polyhydroxysteroids isihippurols A (1) and B (2) were isolated from the MeOH extract of the gorgonian Isis hippuris in addition to nine known steroids namely gorgosterol, 3alpha-acetoxy-24-methyl 11beta,18; 18,20beta; 22,25-triepoxy-5alpha-furostane, hippurin-1, 22-epi-hippuristanol, 22-epi-hippurin-1, 3-acety...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(01)00098-8
更新日期:2001-09-01 00:00:00