Androgen Antagonists: Compounds which inhibit or antagonize the biosynthesis or actions of androgens.Androgens: Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species.Receptors, Androgen: Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.Tosyl CompoundsCyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.Dihydrotestosterone: A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.AnilidesProstatic Neoplasms: Tumors or cancer of the PROSTATE.Androgen Receptor Antagonists: Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Testosterone Congeners: Steroidal compounds related to TESTOSTERONE, the major mammalian male sex hormone. Testosterone congeners include important testosterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with androgenic activities.Metribolone: A synthetic non-aromatizable androgen and anabolic steroid. It binds strongly to the androgen receptor and has therefore also been used as an affinity label for this receptor in the prostate and in prostatic tumors.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Androgen-Insensitivity Syndrome: A disorder of sexual development transmitted as an X-linked recessive trait. These patients have a karyotype of 46,XY with end-organ resistance to androgen due to mutations in the androgen receptor (RECEPTORS, ANDROGEN) gene. Severity of the defect in receptor quantity or quality correlates with their phenotypes. In these genetic males, the phenotypic spectrum ranges from those with normal female external genitalia, through those with genital ambiguity as in Reifenstein Syndrome, to that of a normal male with INFERTILITY.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Piperidines: A family of hexahydropyridines.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Androstenedione: A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Neoplasms, Hormone-Dependent: Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Nandrolone: C18 steroid with androgenic and anabolic properties. It is generally prepared from alkyl ethers of ESTRADIOL to resemble TESTOSTERONE but less one carbon at the 19 position.Androstane-3,17-diol: The unspecified form of the steroid, normally a major metabolite of TESTOSTERONE with androgenic activity. It has been implicated as a regulator of gonadotropin secretion.Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.3-Oxo-5-alpha-Steroid 4-Dehydrogenase: An enzyme that catalyzes the reduction of TESTOSTERONE to 5-ALPHA DIHYDROTESTOSTERONE.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Cell Line, Tumor: A cell line derived from cultured tumor cells.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Dehydroepiandrosterone Sulfate: The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE.Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Estrogens: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Cholestenone 5 alpha-Reductase: An oxidoreductase that catalyzes the conversion of 3-oxo-delta4 steroids into their corresponding 5alpha form. It plays an important role in the conversion of TESTOSTERONE into DIHYDROTESTOSTERONE and PROGESTERONE into DIHYDROPROGESTERONE.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.
The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture. (1/1203)
We have examined five human breast cancer cell lines in continuous tissue culture for androgen responsiveness. One of these cell lines shows a 2- to 4-fold stimulation of thymidine incorporation into DNA, apparent as early as 10 hr following androgen addition to cells incubated in serum-free medium. This stimulation is accompanied by an acceleration in cell replication. Antiandrogens [cyproterone acetate (6-chloro-17alpha-acetate-1,2alpha-methylene-4,6-pregnadiene-3,20-dione) and R2956 (17beta-hydroxy-2,2,17alpha-trimethoxyestra-4,9,11-triene-1-one)] inhibit both protein and DNA synthesis below control levels and block androgen-mediated stimulation. Prolonged incubation (greater than 72 hr) in antiandrogen is lethal. The MCF- cell line contains high-affinity receptors for androgenic steroids demonstrable by sucrose density gradients and competitive protein binding analysis. By cross-competition studies, androgen receptors are distinguishable from estrogen receptors also found in this cell line. Concentrations of steroid that saturate androgen receptor sites in vitro are about 1000 times lower than concentrations that maximally stimulate the cells. Changes in quantity and affinity of androgen binding to intact cells at 37 degrees as compared with usual binding techniques using cytosol preparation at 0 degrees do not explain this difference between dissociation of binding and effect. However, this difference can be explained by conversion of [3H]-5alpha-dihydrotestosterone to 5alpha-androstanediol and more polar metabolites at 37 degrees. An examination of incubation media, cytoplasmic extracts and crude nuclear pellets reveals probable conversion of [3H]testosterone to [3H]-5alpha-dihydrotestosterone. Our data provide compelling evidence that some human breast cancer, at least in vitro, may be androgen dependent. (+info)Pharmacokinetics of flutamide in patients with renal insufficiency. (2/1203)
AIMS: The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD) clearance of flutamide and hydroxyflutamide was also determined. METHODS: Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26 male subjects with normal renal function (creatinine clearance by 24 h urine collection, CLcr, greater than 80 ml min(-1) 1.73 m(-2); n=6) or reduced renal function; CLcr=50-80 (n=7), 30-49 (n=3), 5-29 (n=4), and <5 ml min(-1) 1.73 m(-2)-HD (n=6), following a single, oral 250 mg flutamide dose. Subjects undergoing HD received a second 250 mg dose of flutamide 4 h prior to HD; blood and dialysate were collected during HD to determine dialysability of flutamide and hydroxyflutamide. RESULTS: Cmax, tmax, AUC, t1/2, and renal clearance of flutamide and hydroxyflutamide did not differ between groups. Less than 1% of the dose appeared in dialysate as hydroxyflutamide. No serious adverse events were observed. CONCLUSIONS: Renal function did not affect flutamide nor hydroxyflutamide disposition. HD did not alter hydroxyflutamide pharmacokinetics. Dosing adjustments for renal impairment or HD are not indicated for flutamide. (+info)Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. (3/1203)
Transcription of the prostate-specific antigen (PSA) gene escapes regulation by androgens in advanced prostate cancer. To determine the molecular mechanism(s) of androgen-independent regulation of the PSA gene, the possibility that the androgen receptor (AR) is activated in the absence of androgen by stimulation of protein kinase A (PKA) was investigated. Activation of PKA by forskolin resulted in elevated expression of the PSA gene in androgen-depleted LNCaP cells, an effect that was blocked by the antiandrogen, bicalutamide. Further evidence that induction of PSA gene expression was dependent on AR was obtained from experiments using PC3 cells devoid of AR. Neither PSA, PB, nor ARR3 androgen-responsive reporters could be induced by activation of PKA in the absence of transfected AR. In addition, when nuclear AR from forskolin-treated LNCaP cells was incubated with oligonucleotides encoding an androgen response element of the PSA promoter and examined by electromobility shift assay, an increase in AR-androgen response element complex formation was observed. Lastly, cotransfection of an expression vector for a chimeric protein encoding the amino-terminal domain of the human AR linked to Gal4 and a 5xGal4UAS reporter gene construct resulted in activation of the amino-terminal domain of the AR by stimulation of PKA activity. These results demonstrate androgen-independent induction of PSA gene expression in prostate cancer cells by an AR-dependent pathway. (+info)Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency? (4/1203)
PURPOSE: The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjogren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjogren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis. METHODS: Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects. RESULTS: Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy. CONCLUSIONS: Androgen deficiency may promote the progression of Sjogren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjogren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans. (+info)From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. (5/1203)
Overexpression of the HER2/Neu protooncogene has been linked to the progression of breast cancer. Here we demonstrate that the growth of prostate cancer LNCaP cells can also be increased by the stable transfection of HER2/Neu. Using AG879, a HER2/Neu inhibitor, and PD98059, a MAP kinase inhibitor, as well as MAP kinase phosphatase-1 (MPK-1), in the transfection assay, we found that HER2/Neu could induce prostate-specific antigen (PSA), a marker for the progression of prostate cancer, through the MAP kinase pathway at a low androgen level. Reporter assays and mammalian two-hybrid assays further suggest this HER2/Neu-induced androgen receptor (AR) transactivation may function through the promotion of interaction between AR and AR coactivators, such as ARA70. Furthermore, we found this HER2/Neu --> MAP kinase --> AR-ARAs --> PSA pathway could not be blocked completely by hydroxyflutamide, an antiandrogen used in the treatment of prostate cancer. Together, these data provide a novel pathway from HER2/Neu to AR transactivation, and they may represent one of the reasons for the PSA re-elevation and hormone resistance during androgen ablation therapy in prostate cancer patients. (+info)Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations. (6/1203)
Differential gene expression between the androgen sensitive human prostate cancer cell line LNCaP and an insensitive clonal variant, LNCaP-r, was demonstrated by suppression subtractive hybridization. Twenty-one sequences were identified of which 9 are homologous to known genes, 11 are represented by expressed sequence tags (ESTs), and 1 is novel. We present data for 5 of 7 sequences confirmed to be differentially expressed by Northern blot analysis and semiquantitative RT-PCR. Only one gene, fibronectin (FN), was highly overexpressed (>60-fold) in LNCaP-r cells, consistent with previously reported overexpression of FN in prostate cancer. Four sequences were down-regulated in LNCaP-r cells, including an inactive variant of the E2 ubiquitin conjugating enzyme (UEV-1), a novel metalloproteinase-related collagenase (PM5), and a potential tumor suppressor gene (breast basic conserved gene, BBC1). UEV-1 is multifunctional, regulates the cell cycle via cdk1, has homology to MMS2 and likewise functions as a DNA protection protein, and also has homology to TSG101. Aberrant splice variants of TSG101 occur frequently in both breast and prostate cancer, but its mechanism of action is unknown. FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression. (+info)Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer. (7/1203)
The INK4A gene maps to the 9p21 region and was initially described [M. Serrano et al., Nature (Lond.), 366: 704-707, 1993; A. Kamb et al., Science (Washington DC), 264: 436-440, 1994] as encoding a 148-amino-acid protein termed p16. The p16 protein associates exclusively with Cdk4 and Cdk6, inhibiting their complexation with D-type cyclins and the consequent phosphorylation of pRb. This contributes to cell cycle arrest. The purpose of the present study was to evaluate patterns of p16 expression in a well-characterized cohort of prostatic adenocarcinomas while exploring potential associations between alterations of p16 and clinicopathological variables. Normal and malignant tissues from 88 patients with prostate carcinoma were examined. In situ hybridization and immunohistochemistry assays were used to determine the status of the INK4A exon 1alpha transcripts and levels of p16 protein, respectively. Associations between altered patterns of expression and clinicopathological variables, including pretreatment prostate-specific antigen (PSA) level, Gleason grade, pathological stage, and hormonal status, were evaluated using the Mantel-Haenszel chi2 test. Biochemical (PSA) relapse after surgery was evaluated using the Kaplan-Meier method and the log-rank test. Levels of p16 expression and INK4A exon 1alpha transcripts in normal prostate and benign hyperplastic tissues were undetectable. However, p16 nuclear overexpression was observed in 38 (43%) prostate carcinomas, whereas the remaining 50 (57%) cases showed undetectable p16 levels. Overexpression of p16 protein was found to correlate with increased INK4A exon 1alpha transcripts. Moreover, p16 overexpression was associated with a higher pretreatment PSA level (P = 0.018), the use of neoadjuvant androgen ablation (P = 0.001), and a sooner time to PSA relapse after radical prostatectomy (P = 0.002). These data suggest that p16 overexpression is associated with tumor recurrence and a poor clinical course in patients with prostate cancer. (+info)Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. (8/1203)
The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment. (+info)... s, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like ... N-Terminal domain antagonists[edit]. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all ... Androgen antagonists; Androgen blockers; Testosterone blockers. Use. • Men and boys: Prostate cancer; Benign prostatic ... Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3 ...
Tindall, D.J.; Chang, C.H.; Lobl, T.J.; Cunningham, G.R. (1984). "Androgen antagonists in androgen target tissues". ... Lerner, Leonard J. (1975). "Androgen antagonists". Pharmacology & Therapeutics. Part B: General and Systematic Pharmacology. 1 ... It was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and ...
"Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3): 367-400. PMID 6205409. Singh SM, Gauthier S, Labrie ... It is a selective antagonist of the androgen receptor and consequently has progonadotropic effects by increasing gonadotropin ... "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211-47. PMID 10637363 ... Thomson, D. S. (1989). "Pharmacology of Anti-androgens in the Skin". 87 / 2: 483-493. doi:10.1007/978-3-642-74054-1_36. ISSN ...
Ran F, Xing H, Liu Y, Zhang D, Li P, Zhao G (2015). "Recent Developments in Androgen Receptor Antagonists". Arch. Pharm. ( ... RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) which was first described in 1994 and was ... RU-59063 has high affinity for the human androgen receptor (AR) (Ki = 2.2 nM; Ka = 5.4 nM) and 1,000-fold selectivity for the ... Liu B, Su L, Geng J, Liu J, Zhao G (2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ...
They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211-47. doi:10.2174/ ... An over-the-counter histamine H2 receptor antagonist that also shows very weak activity as an AR antagonist. Also inhibits ...
Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP (July 2002). "Bicalutamide functions as an androgen receptor antagonist by ... Bicalutamide acts as a highly selective competitive silent antagonist of the androgen receptor (AR) (IC50 = 159-243 nM), the ... Antigonadotropic agents like high-dose CPA, high-dose androgens (e.g., testosterone esters), and GnRH antagonists (though ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ...
They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like ... Specifically acts as an AR antagonist, weak antigonadotropin, and weak steroidogenesis inhibitor. Used for androgen-dependent ... 99-. ISBN 978-1-60327-829-4. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ... Due to their antigonadotropic effects, SAAs lower androgen levels in addition to directly blocking the actions of androgens at ...
... acts as a selective antagonist of the androgen receptor (AR), competing with androgens like testosterone and ... Helsen C, Van den Broeck T, Voet A, Prekovic S, Van Poppel H, Joniau S, Claessens F (Aug 2014). "Androgen receptor antagonists ... Sundblad C, Landén M, Eriksson T, Bergman L, Eriksson E (2005). "Effects of the androgen antagonist flutamide and the serotonin ... In contrast to GnRH agonists, GnRH antagonists don't cause an initial androgen surge, and are gradually replacing GnRH agonists ...
321-. ISBN 978-1-901865-55-4. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ...
Similarly to flutamide, AA560 is a selective antagonist of the androgen receptor (AR) and consequently shows progonadotropic ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ...
Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... ISBN 978-1-4831-4566-2. R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 [44], is a powerful ... Brueggemeier, Robert W. (2006). "Sex Hormones (Male): Analogs and Antagonists". doi:10.1002/3527600906.mcb.200500066. ... derivative which was never marketed for medical use but has been widely used in scientific research as a hot ligand in androgen ...
In fact, it is actually an antagonist of the androgen receptor (AR) and hence has antiandrogenic activity, said to be about 30 ... 63-. ISBN 978-3-319-20185-6. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ... It shows antagonist activity by binding to the AR, and hence produces an antiandrogenic action equivalent to ca. 40% of the ... Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen ...
... acts as a selective antagonist of the androgen receptor (AR), preventing the effects of androgens like testosterone ... Nilutamide acts as a selective competitive silent antagonist of the AR (IC50 = 412 nM), which prevents androgens like ... 11-. ISBN 978-981-256-920-2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... De Voogt, H. J.; Rao, B. R.; Geldof, A. A.; Gooren, L. J. G.; Bouman, F. G. (1987). "Androgen action blockade does not result ...
Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... ISBN 978-1-60327-829-4. Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): ... "Androgen receptor antagonists for prostate cancer therapy". Endocrine-Related Cancer. 21 (4): T105-18. doi:10.1530/ERC-13-0545 ... "Drug safety is a barrier to the discovery and development of new androgen receptor antagonists". The Prostate. 71 (5): 480-8. ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Differential effects on high-androgen responder and low-androgen responder muscle groups". Endocrinology. 154 (12): 4594-606. ... It is reported to possess an IC50 of 700 nM for the androgen receptor (AR), about 4-fold less than that of bicalutamide. ...
CPA is a potent androgen receptor (AR) competitive antagonist. It directly blocks endogenous androgens such as testosterone and ... CPA is known to possess the following pharmacological activity: Androgen receptor (AR) antagonist/very weak partial agonist ( ... ISBN 978-1-84076-013-2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... In addition, although CPA reduces androgen production in the gonads, it can increase the production of adrenal androgens, in ...
ISBN 978-3-527-30247-5. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ...
Gauthier S, Martel C, Labrie F (October 2012). "Steroid derivatives as pure antagonists of the androgen receptor". The Journal ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... In the cortex and pituitary, androgens do not undergo significant aromatization, and it appears that the effects of androgens ... Balk SP (September 2002). "Androgen receptor as a target in androgen-independent prostate cancer". Urology. 60 (3 Suppl 1): 132 ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Seborrhea is recognized as an androgen-sensitive condition - that is, it is caused or aggravated by androgen sex hormones such ... "Androgen Physiology, Pharmacology and Abuse". PMID 25905231. Kenneth L. Becker (2001). Principles and Practice of Endocrinology ... Zouboulis, Christos C.; Degitz, Klaus (2004). "Androgen action on human skin - from basic research to clinical significance". ...
Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... List of androgens/anabolic steroids R.A. Hill; H.L.J. Makin; D.N. Kirk; G.M. Murphy (23 May 1991). Dictionary of Steroids. CRC ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Rosterolone is a derivative of mesterolone, which, in contrast, is an androgen and anabolic steroid. Steroidal antiandrogen ...
... acts as a selective silent antagonist of the androgen receptor (AR), the biological target of androgens like ... Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... "Drug safety is a barrier to the discovery and development of new androgen receptor antagonists". The Prostate. 71 (5): 480-8. ... "Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC ...
... is a selective competitive antagonist of the androgen receptor (AR), although it is described as an "only relatively weak ... ISBN 978-1-4831-6510-3. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... is not an androgen antagonist within the central nervous system". Steroids. 34 (2): 139-149. doi:10.1016/0039-128X(79)90043-6. ... On the basis of animal research, BOMT does not appear to act as an AR antagonist in central nervous system tissues, and in ...
Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... Kawahara, Takashi; Miyamoto, Hiroshi (2014). "Androgen Receptor Antagonists in the Treatment of Prostate Cancer". Clinical ... acting as a selective competitive antagonist of the androgen receptor (AR), but shows some advantages, including greater ... a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Seborrhoea is recognized as an androgen-sensitive condition - that is, it is caused or aggravated by androgen sex hormones such ... In accordance with the involvement of androgens in seborrhoea, antiandrogens, such as cyproterone acetate,[30] spironolactone,[ ... Zouboulis, Christos C.; Degitz, Klaus (2004). "Androgen action on human skin - from basic research to clinical significance". ...
Androgen receptor modulators. Progesterone receptor modulators. List of estrogens. This article about a steroid is a stub. You ... Antagonists. *(R,R)-THC. *7β-Hydroxy-DHEA. *Chloroindazole. *Cytestrol acetate. *EM-800 (SCH-57050) ...
Pharmacological Actions : Androgen Antagonists, Antiproliferative , Wnt/β-catenin signaling pathway modulation. Additional ... 6 Abstracts with Androgen Antagonists Research. Filter by Study Type. Animal Study. ... A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic mice. Oct 15, 2008. ... A compound within Pygeum bark antagonizes human androgen receptor in the prostate gland. Sep 23, 2009. ...
Androgen antagonist synonyms, Androgen antagonist pronunciation, Androgen antagonist translation, English dictionary definition ... of Androgen antagonist. n. A substance that inhibits the biological effects of androgenic hormones ... 18) Low androgen levels, such as in those who are androgen deficient or using androgen antagonists, can result in reduced ... Androgen antagonist - definition of Androgen antagonist by The Free Dictionary https://www.thefreedictionary.com/Androgen+ ...
Androgen Antagonists Overview. Androgen Antagonists Disease Associated. Androgen Antagonists Pipeline Therapeutics. Androgen ... Androgen Antagonists Assessment by Molecule Type. Androgen Antagonists Assessment by Stage and Molecule Type. Androgen ... Androgen Antagonists Assessment by Combination Products. Androgen Antagonists Assessment by Route of Administration. Androgen ... Androgen Antagonists Assessment by Combination Products. Androgen Antagonists Assessment by Route of Administration. Androgen ...
An androgen receptor N-terminal domain antagonist for treating prostate cancer. Jae-Kyung Myung,1 Carmen A. Banuelos,1 Javier ... Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J Biol Chem. ... The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced ... Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009;138(2):245-256 ...
"Androgen Antagonists" by people in Harvard Catalyst Profiles by year, and whether "Androgen Antagonists" was a major or minor ... "Androgen Antagonists" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Androgen Antagonists" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Androgen Antagonists". ...
Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as nonsteroidal androgen receptor antagonists.. [ ...
Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists ... Analogues inhibit AR-mediated reporter gene expression and bind to AR as potently as or better than any known AR antagonists. ... Androgen receptor / NR3C4 - data and references - Guide to Pharmacology. Miscellaneous. *TESTOSTERONE - Hazardous Substances ... A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human androgen ...
A series of nonsteroidal human androgen receptor (hAR) antagonists based on 8-substituted 1,2-dihydro- and 1,2,3,4-tetrahydro-2 ... Effects of isosteric pyridone replacements in androgen receptor antagonists based on 1,2-dihydro- and 1,2,3,4-tetrahydro-2,2- ... Androgen Antagonists/chemical synthesis*. *Androgen Antagonists/pharmacology. *Androgen Receptor Antagonists*. *Androgens/ ...
Galeterone is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, ... Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. ... Bicalutamide is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. ... Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. ...
... is androgen-receptor inhibitor. Highly recommended inhibitor in AR research. Find all the information about MDV3100 ( ... Galeterone is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, ... Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. ... Bicalutamide is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. ...
... antagonists for the androgen receptor are disclosed. Also disclosed are methods for employing the disclosed compounds for ... modulating processes mediated by the androgen receptor and for treating patients requiring androgen receptor antagonist therapy ... androgen receptor antagonist therapy.. Claim:. We claim:. 1. A method of antagonizing androgen activity comprising the in vivo ... steroid androgen receptor antagonist compounds disclosed can be readily utilized in pharmacological applications where androgen ...
1998) Assays to Measure Estrogen and Androgen Agonists and Antagonists. In: del Mazo J. (eds) Reproductive Toxicology. Advances ... Olea, N., Sakabe, K., Soto, A.M. and Sonnenschein, C., 1990, The proliferative effect of "anti-androgens" on the androgen- ... DDE is a potent androgen receptor antagonist, Nature. 375: 581.PubMedCrossRefGoogle Scholar ... Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor, ...
... but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in ... Persistent DDT metabolite p,p-DDE is a potent androgen receptor antagonist Nature. 1995 Jun 15;375(6532):581-5. doi: 10.1038/ ... they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT ... DDE and related environmental chemicals may be mediated at the level of the androgen receptor. ...
Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer.. Youzhi Tong, Chunyun ... Androgen Receptor (AR) antagonists have been used in clinic to treat prostate cancer. One example is bicalutamide (Casodex®), ... Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. [abstract]. In: Proceedings of the ... Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. ...
Bradykinin Receptor Antagonists. Class Summary. Bradykinin receptor antagonists such as icatibant inhibit bradykinin from ... Androgens. Class Summary. Oral androgens have provided the most successful preventive therapy. Synthetic attenuated androgens ( ... Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline]. ... Hepatotoxicity (more commonly observed in the group receiving 17 alpha alkylated androgen) has not been observed. Oxandrolone ...
GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ...
Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res 1999; 59: 2511-5. ... The mechanisms by which androgen receptor (AR) antagonists inhibit AR activity, and how their antagonist activity may be ... antagonist. Introduction. The androgen receptor (AR) plays a central role in prostate cancer development and progression, and ... Activity of Androgen Receptor Antagonist Bicalutamide in Prostate Cancer Cells Is Independent of NCoR and SMRT Corepressors. ...
... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ...
We report here the design and synthesis of novel androgen antagonists bearing carborane. The most potent compounds, the ... Further development of the potent carborane-containing androgen antagonists described here, having a new skeletal structure and ... as well as in cell growth inhibition assay using androgen-dependent SC-3 cells. ... unique characteristics, may yield novel therapeutic agents, especially selective androgen receptor modulators. ...
The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate ... The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate ... Inhibition of human AR by androgen ablation therapy and by applying synthetic anti-androgens is therefore the primary goal in ... Importantly, AA is able to efficiently repress the growth of both the androgen-dependent LNCaP and also the androgen- ...
The effects of natural ligands of hormone receptors and their antagonists on telomerase activity in the androgen sensitive ... The effects of natural ligands of hormone receptors and their antagonists on telomerase activity in the androgen sensitive ... antagonists tamoxifen and bicalutamide on telomerase activity and expression of cell cycle related proteins in the androgen- ... antagonists tamoxifen and bicalutamide on telomerase activity and expression of cell cycle related proteins in the androgen- ...
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like ... N-Terminal domain antagonists[edit]. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all ... Androgen antagonists; Androgen blockers; Testosterone blockers. Use. • Men and boys: Prostate cancer; Benign prostatic ... Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3 ...
Androgen Antagonists. Androgen antagonists prevent the growth of prostate cancer cells and induce a G1 cell cycle arrest. The ... We are studying the effect of these antagonists on p27, cyclin E, and cyclin D/cdk complexes. We are also interested in ...
Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or ... Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen ... glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin which ...
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. Androgen ... and then stimulates transcription of androgen responsive genes. The androgen receptor is most closely related to the ... Mutations in this gene are also associated with complete androgen insensitivity (CAIS) ... Androgen receptor (AR) is a type of nuclear receptor that is activated by binding of either of the androgenic hormones ...
DeprivationHuman androgen receptorFlutamideLuteinizing hormoneAgonistsGnRHEstrogenDihydrotestosteroneAntiandrogensBicalutamideMDV3100SteroidSecond-generation androgen receptorLevels of androgensActions of androgensInhibitorTherapyTreatment of androgen-dependent skinAntiandrogenEndogenousAgonistAbstractEnzalutamideInhibit androgen receptorLNCaPCastration-resistantAnti-androgen effectInhibits androgen receptorBiosynthesisInduceInhibitionReceptor expressionSyntheticTranscriptional activityMeSHSurgical castrationOrally
- This new drug is the latest breakthrough for the treatment of advanced cases and is the first-in-class intracrine androgen antagonist for patients whose cancer has stopped responding to androgen deprivation therapy (ADT). (thefreedictionary.com)
- D'Amico AV. Post-operative salvage androgen deprivation and radiotherapy for prostate cancer. (harvard.edu)
- Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database. (harvard.edu)
- The mechanisms by which androgen receptor (AR) antagonists inhibit AR activity, and how their antagonist activity may be abrogated in prostate cancer that progresses after androgen deprivation therapy, are not clear. (aacrjournals.org)
- The androgen receptor (AR) plays a central role in prostate cancer development and progression, and androgen deprivation therapy by suppression of testicular androgen production (surgical castration or administration of luteinizing hormone-releasing hormone superagonists), or by treatment with AR antagonists (flutamide or bicalutamide), is still the standard systemic treatment. (aacrjournals.org)
- Additional mechanisms that may contribute to AR reactivation after androgen deprivation therapy are increased AR expression, including AR gene amplification that occurs in approximately one third of patients, and AR mutations that can enhance responses to nonandrogen steroids and to antagonists ( 6 - 9 ). (aacrjournals.org)
- In accordance, therapeutic modalities that reduce androgen signaling in the prostate gland, referred to collectively as androgen deprivation therapy , are able to significantly slow the course of prostate cancer and extend life in men with the disease. (wikipedia.org)
- Although antiandrogens are effective in slowing the progression of prostate cancer, they are not generally curative, and with time, the disease adapts and androgen deprivation therapy eventually becomes ineffective. (wikipedia.org)
- The most common methods of androgen deprivation therapy currently employed to treat prostate cancer are castration (with a GnRH modulator or orchiectomy ), nonsteroidal antiandrogens, and the androgen synthesis inhibitor abiraterone acetate . (wikipedia.org)
- Compare the survival of patients with metastatic stage IV prostate cancer responsive to combined androgen-deprivation therapy (CAD) treated with intermittent vs continuous CAD. (clinicaltrials.gov)
- Induction therapy: Patients receive combined androgen-deprivation (CAD) therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily for 8 courses (7 months). (clinicaltrials.gov)
- This phase II trial studies how well docetaxel or abiraterone acetate work when combined with androgen deprivation therapy (ADT) in treating patients with hormone sensitive prostate cancer that has spread to other parts of the body. (clinicaltrials.gov)
- Participants receive androgen deprivation therapy (ADT) per standard of care and docetaxel IV over 1 hour on day 1. (clinicaltrials.gov)
- Participants receive androgen deprivation therapy (ADT) per standard of care, abiraterone acetate PO daily, and prednisone PO twice daily. (clinicaltrials.gov)
- Therefore, androgen deprivation therapy and inhibition of the AR-signaling by AR antagonists are the major forms of PCa hormone therapy. (biomedcentral.com)
- BACKGROUND: There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. (biomedsearch.com)
- However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. (biomedsearch.com)
- The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. (biomedsearch.com)
- METHODS/DESIGN: We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. (biomedsearch.com)
- 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. (biomedsearch.com)
- DISCUSSION: This project is unique as it explores a fundamental question of when exercise implementation will be of most benefit and addresses both physical and psychological consequences of androgen deprivation initiation. (biomedsearch.com)
- The final outcome may be adjunct treatment which will reduce if not prevent the toxicities of androgen deprivation, ultimately resulting in reduced morbidity and mortality for men with prostate cancer. (biomedsearch.com)
- Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. (bcgsc.ca)
- Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists]. (urotoday.com)
- Several studies have indicated that reduction of testosterone levels in patients with prostate cancer undergoing androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists can be associated with an increased risk of cardiovascular events. (urotoday.com)
- Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists-a nationwide population-based cohort study based on 2010-2013 French Health Insurance data. (urotoday.com)
- Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. (urotoday.com)
- Androgen deprivation therapy (ADT) has been the mainstay of treatment for advanced prostate cancer for decades, and has been shown to control disease and improve symptoms. (urotoday.com)
- This therapy is known as Androgen Deprivation Therapy or ADT. (fda.gov)
- Androgen deprivation therapy , also called ADT, uses surgery or medicines to lower the levels of androgens made in the testicles. (cancer.org)
- His lab developed methods to analyze advanced metastatic PCa through the use of bone marrow biopsies and showed that one mechanism for disease progression after androgen deprivation therapy was through mutations in the androgen receptor (AR). (bidmc.org)
- In subsequent studies his lab has further established a critical role for AR in PCa that relapses after androgen deprivation therapy, and identified mechanisms that mediate AR reactivation (including enhanced androgen synthesis by tumor cells). (bidmc.org)
- Ishizaki et al (2013) Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer. (tocris.com)
- A Novel GPCR Target in correlation with Androgen Deprivation Therapy for Prostate Cancer Drug Discovery. (physiciansweekly.com)
- A compound within Pygeum bark antagonizes human androgen receptor in the prostate gland. (greenmedinfo.com)
- A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human androgen receptor (hAR). (nih.gov)
- A series of nonsteroidal human androgen receptor (hAR) antagonists based on 8-substituted 1,2-dihydro- and 1,2,3,4-tetrahydro-2,2-dimethyl-6-trifluoromethylpyrido[3,2-g]quin olines was synthesized. (nih.gov)
- The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate cancer cell growth. (curehunter.com)
- The ligand-activated human androgen receptor (AR) supports the growth of the prostate gland. (curehunter.com)
- Mutant ARs that are strongly stimulated by the AR antagonist flutamide have been found in approximately one third of patients who relapse after combination therapy with flutamide, and a distinct mutant AR that is strongly stimulated by bicalutamide has been found in long-term bicalutamide-treated patients, but such mutations are uncommon in patients treated with surgical or medical castration monotherapy ( 9 , 11 ). (aacrjournals.org)
- Unlike flutamide and nilutamide, the drug is said to be short-acting and inactive by injection, but it has been found to be active topically in animals, and hence could be useful for the treatment of androgen-dependent skin conditions. (wikipedia.org)
- To evaluate whether, by blocking androgen action, flutamide can decrease and normalize vascular resistance in the uterine artery in patients with polycystic ovary syndrome (PCOS). (curehunter.com)
- It is used along with long-acting gonadotropin antagonists such as leuprolide as an effective and less toxic alternative to flutamide, and has now become the most commonly used, with a single daily dose protocol. (news-medical.net)
- These mutations occur specifically in patients treated with an AR antagonist, flutamide, and are the result of strong selective pressure exerted by this drug. (bidmc.org)
- 3. The method according to claim 2, wherein the androgen antagonist is selected from the group consisting of bicalutamide, flutamide, hydroxyflutamide, nilutamide and cyproterone acetate. (freepatentsonline.com)
- Degarelix (Firmagon), a gonadotropin-releasing hormone (GnRH) receptor antagonist differs from luteinizing hormone-releasing hormone (LHRH) agonists by avoiding "testosterone flare" and lower follicle-stimulating hormone (FSH) levels. (aacrjournals.org)
- and d) select standard reference doses of TP and FLU for future studies with weakly potent agonists, antagonists, and nonandrogenic test substances. (thefreedictionary.com)
- Interestingly, cellular senescence in prostate cancer (PCa) cells can be induced by either androgen receptor (AR) agonists at supraphysiological androgen level (SAL) used in bipolar androgen therapy or by AR antagonists. (biomedcentral.com)
- A small screen of AR-binding ligands, including known agonists, antagonists, and endocrine disruptors, demonstrated that nuclear translocation and nuclear "speckling" were linked with transcriptional output, and specific ligands were noted to differentially affect measurements for wild type versus mutant AR, suggesting differing mechanisms of action. (nih.gov)
- As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC 50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC 50 of 1-2 μM). (pubmedcentralcanada.ca)
- What are the two GnRH antagonists to know? (flashcardmachine.com)
- MOA of the GnRH antagonists? (flashcardmachine.com)
- Therefore, androgen replacement must be included in any GnRH antagonist regimen used in human male contraception. (washington.edu)
- We tested the hypothesis that the combination of a GnRH antagonist plus T would suppress spermatogenesis in the male primate to azoospermic levels while maintaining normal serum T levels. (washington.edu)
- We examined the effects of the GnRH antagonist Deterelix [N-Ac-DNal(2)1-DpCl-Phe2-DTrp3-DhArg(Et2)6 -DAla10-GnRH], alone and with simultaneous T replacement, on sperm production and serum T levels in adult male monkeys (n = 22). (washington.edu)
- We conclude that the combination of a GnRH antagonist plus T can induce azoospermia reversibly in this nonhuman primates species, and that a similar combination may be an effective contraceptive regimen in men. (washington.edu)
- The GnRH antagonist alone may be an effective treatment for androgen-dependent neoplasia. (washington.edu)
- Dehydroepiandrosterone is an important endogenous steroid hormone, which is an androgen receptor antagonist and an estrogen receptor agonist. (selleckchem.com)
- However, because estrogens are made from androgens in the body, antiandrogens that suppress androgen production can cause low estrogen levels and associated symptoms like hot flashes, menstrual irregularities , and osteoporosis in premenopausal women. (wikipedia.org)
- It is recommended that MTFs take both an anti-androgen and a source of estrogen before having an orchiectomy, and discontinue using anti-androgens after an orchiectomy (Asscheman & Gooren). (trans-health.com)
- Although EDCs affect a broad range of endocrine functions in different tissues and organs, many studies have focused on the estrogen signaling pathway [ 6 ] and fewer on the androgen or other hormonal signaling pathways. (pubmedcentralcanada.ca)
- The effects of the 17beta-estradiol, dihydrotestosterone and hormone antagonists tamoxifen and bicalutamide on telomerase activity and expression of cell cycle related proteins in the androgen-sensitive prostatic cancer cell line LNCaP were studied. (uni-regensburg.de)
- 17beta-estradiol stimulated cell growth more effectively than dihydrotestosterone whereas hormone antagonists tamoxifen and bicalutamide caused a significant decrease in cell viability. (uni-regensburg.de)
- Antiandrogens are one of three types of sex hormone antagonists , the others being antiestrogens and antiprogestogens . (wikipedia.org)
- Antiandrogens are used to treat an assortment of androgen-dependent conditions . (wikipedia.org)
- In women, antiandrogens are used to treat acne , seborrhea , excessive hair growth , scalp hair loss, and high androgen levels , such as those that occur in polycystic ovary syndrome (PCOS). (wikipedia.org)
- In women, antiandrogens are much better tolerated , and antiandrogens that work only by directly blocking androgens are associated with minimal side effects. (wikipedia.org)
- Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both males and females. (wikipedia.org)
- Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both men and women. (wikipedia.org)
- For these reasons, they have improved efficacy and selectivity as antiandrogens and do not lower androgen levels, instead acting solely by directly blocking the actions of androgens at the level of their biological target, the AR. (wikipedia.org)
- Both conditions represent abnormal growth patterns that often exhibit a significant degree of androgen dependence, which could be antagonized by antiandrogens. (springer.com)
- Antiandrogens are molecules that compete with androgens to bind in the ligand binding site of the AR. (news-medical.net)
- All test systems showed that bicalutamide and hydroxyflutamide act as potent androgen antagonists (Ma et al. (thefreedictionary.com)
- Elevated AR expression in tumor cells correlates with a change in the functional activity of bicalutamide from antagonist to agonist, suggesting that prostate tumors may adapt to survive on any residual agonism. (aacrjournals.org)
- MDV3100, a more potent AR antagonist (∼5x vs bicalutamide) without residual agonism, has demonstrated excellent efficacy in CRPC patients and has been approved by FDA for treating CRPC in clinic. (aacrjournals.org)
- We first show that the agonist activities of weak androgens and an AR antagonist (cyproterone acetate) are still dependent on the AR NH 2 /COOH-terminal interaction and are enhanced by steroid receptor coactivator (SRC)-1, whereas the bicalutamide-liganded AR did not undergo a detectable NH 2 /COOH-terminal interaction and was not coactivated by SRC-1. (aacrjournals.org)
- Taken together, these results indicate that bicalutamide lacks agonist activity and functions as an AR antagonist due to ineffective recruitment of coactivator proteins and that enhanced coactivator recruitment, rather than loss of corepressors, may be a mechanism contributing to bicalutamide resistance. (aacrjournals.org)
- However, these responses are usually partial and transient, with AR activity becoming resistant to even high doses of the AR antagonist bicalutamide through unclear mechanisms ( 5 ). (aacrjournals.org)
- Increased AR expression can enhance the growth of prostate cancer xenografts in castrated mice and has been reported to enhance the agonist activity of the AR antagonist bicalutamide ( 10 ). (aacrjournals.org)
- 50 microM of bicalutamide down-regulated the levels of the androgen receptor, the proliferating cell nuclear antigen and telomerase activity, and up-regulated the expression of p27(Kip1). (uni-regensburg.de)
- Bicalutamide , a nonsteroidal antiandrogen and the most widely used androgen receptor antagonist in the treatment of prostate cancer . (wikipedia.org)
- When castration is combined with a nonsteroidal antiandrogen like bicalutamide , this strategy is referred to as combined androgen blockade (also known as complete or maximal androgen blockade). (wikipedia.org)
- MDV3100 also binds to the androgen receptor with a greater relative affinity than the clinically used antiandrogen bicalutamide (Casodex), Dr. Sawyers and colleagues said. (medpagetoday.com)
- Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. (selleckchem.com)
- Amajor metabolite of Enzalutamide (MDV3100) which is an androgen-receptor (AR) antagonist for treatment of prostate cancer. (raystarbio.cn)
- MDV3100 is a novel antagonist of AR that is also in phase III clinical trials. (aacrjournals.org)
- Despite encouraging clinical results with next generation drugs (MDV3100 and abiraterone) that inhibit androgen receptor (AR) signaling in patients with castration-resistant prostate cancer (CRPC), responses are variable and short-lived. (biomedsearch.com)
- Androgens are steroid hormones that possess virilizing actions and, consequently, serve to stimulate differentiation and maintenance of the androgen-dependent tissues of the male reproductive system. (springer.com)
- Glucocorticoids such as prednisone, exert a negative feedback mechanism on central stimulation of steroid production, thus preventing adrenal androgen production. (news-medical.net)
- Aragon's lead product candidate is a second generation androgen receptor signaling inhibitor, ARN-509, in Phase 2 development for castration resistant prostate cancer (CRPC). (bio-medicine.org)
- This belief has persisted despite the fact that there is no scientific evidence to date that shows that increased levels of androgens down regulates the androgen receptor in muscle tissue. (anabolicminds.com)
- This increased activity is independent of androgens and explains the poor correlation between systemic levels of androgens and the severity of acne lesions. (thefreedictionary.com)
- Synthetic attenuated androgens (eg, danazol, oxandrolone) taken prophylactically increase the serum concentration of C1 inhibitor (C1INH), presumably by enhancing the function of the C1INH gene ( SERPING1 ). (medscape.com)
- Other forms of therapy include androgen antagonist drugs such as ketoconazole, finasteride and insulin-sensitizing drugs such as metformin. (thefreedictionary.com)
- Oral androgens have provided the most successful preventive therapy. (medscape.com)
- Inhibition of human AR by androgen ablation therapy and by applying synthetic anti- androgens is therefore the primary goal in treatment of patients. (curehunter.com)
- Antihormone therapy, such as ADT may lessen the amount of androgen made by the body. (clinicaltrials.gov)
- The finding that somatostatin analog RC-160 and bombesin/GRP antagonist RC-3095 inhibit the growth of androgen-independent prostate tumors in mice might be of practical importance for human prostate cancer therapy. (elsevier.com)
- The principal clinical uses of the androgens include replacement therapy in hypogonadism and anabolic stimulation in states of negative nitrogen balance. (springer.com)
- Hormone therapy is also called androgen suppression therapy . (cancer.org)
- Not as effective for MTF hormone therapy, because it can potentially stimulate androgen production. (trans-health.com)
- 2. The method according to claim 1, wherein the prostate carcinoma is therapy-resistant to androgen antagonists. (freepatentsonline.com)
- be useful for the topical treatment of androgen-dependent skin disorders such as acne, androgenetic alopecia and hirsutism. (raystarbio.cn)
- It was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and was found to produce some benefit. (wikipedia.org)
- Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. (nih.gov)
- Prostate cancer becomes resistant to antiandrogen drugs when cancer cells begin to increase production of the androgen receptor, Dr. Sawyers noted in a statement. (medpagetoday.com)
- The normal development and function of the male reproductive system is dependent on the action of endogenous androgens (review and references therein, [ 10 ]) and the biological functions of androgens are primarily mediated by the AR [ 13 , 14 ], which is expressed in many organs including the hypothalamus, pituitary, liver, prostate, and testes. (pubmedcentralcanada.ca)
- Surprisingly, ABT263 lacks senolytic effect in both AR agonist- and antagonist-pretreated cells. (biomedcentral.com)
- These data indicate a difference in the agonist- or antagonist-induced cellular senescence and suggest a novel role of MK2206 as a senolytic agent preferentially for AR antagonist-treated cells. (biomedcentral.com)
- Taken together, our data suggest that both AR agonist and antagonist induce cellular senescence but differentially upregulate a pro-survival signaling which preferentially sensitize androgen-sensitive PCa LNCaP cells to a specific senolytic compound. (biomedcentral.com)
- Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. (aacrjournals.org)
- abstract = "Nude mice bearing xenografts of the androgen-independent human prostate cancer DU-145 were treated for 4-5 weeks with somatostatin analog RC-160 or the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095. (elsevier.com)
- Purpose: Enzalutamide, a second-generation androgen antagonist, was approved by the U.S. Food and Drug Administration (FDA) for castration-resistant prostate cancer (CRPC) treatment. (elsevier.com)
- Relative to enzalutamide and apalutamide, shows greater efficacy as an AR antagonist, improved activity against mutated AR variants in prostate cancer, little or no inhibition or induction of cytochrome P450 enzymes, and little or no central nervous system distribution. (wikipedia.org)
- Similar to enzalutamide and apalutamide, but with increased efficacy as an AR antagonist, little or no central nervous system distribution, and no induction of seizures in animals. (wikipedia.org)
- Here, we first induced cellular senescence by treating androgen-sensitive PCa LNCaP cells with either SAL or the AR antagonist Enzalutamide (ENZ). (biomedcentral.com)
- Oral curcumin intake could inhibit androgen receptor expression and probably PSA activity. (greenmedinfo.com)
- Importantly, AA is able to efficiently repress the growth of both the androgen-dependent LNCaP and also the androgen-independent C4-2 Pca cells but not that of PC3 or CV1 cells lacking AR. (curehunter.com)
- Treatment of human prostate carcinoma‐derived LNCaP cells with androgen or oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor β with Src, activates the Src/Raf‐1/Erk‐2 pathway and stimulates cell proliferation. (embopress.org)
- The majority of patients have clinical and biochemical [decrease in serum prostate-specific antigen (PSA)] evidence of improvement but eventually relapse with a more aggressive form of prostate cancer that has been termed hormone-refractory, castration-resistant, or androgen-independent prostate cancer. (aacrjournals.org)
- Castration, therefore, does not suppress adrenal androgens and achieves a "hormone-reduced" rather than a "hormone-free" state, hence, the recent renaming of this stage of the disease as castration-resistant in preference to hormone-refractory. (aacrjournals.org)
- Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic. (bcgsc.ca)
- Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). (bcgsc.ca)
- Limited clinical data indicate that daily supplementation with DIM may benefit patients with castration-resistant prostate cancer by inhibiting androgen receptor (20) . (mskcc.org)
- Peppermint tea has an anti-androgen effect in rats. (greenmedinfo.com)
- A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic mice. (greenmedinfo.com)
- The compound, being developed by Medivation, of San Francisco, blocks the androgen receptor and also inhibits androgen receptor function by preventing nuclear translocation of the receptor and DNA binding. (medpagetoday.com)
- in androgen biosynthesis and the.Na+,K+-ATPase in Skeletal Muscle: Significance of Exercise and Thyroid Hormones for. (tylerweitzman.tk)
- Androgen antagonists prevent the growth of prostate cancer cells and induce a G1 cell cycle arrest. (mskcc.org)
- Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. (nih.gov)
- Anti-androgenic activity of various phthalimide analogs was evaluated based on inhibition of androgen-induced activation of nuclear androgen receptor (CAT assay) and on growth inhibition of the androgen-dependent clonal cell line SC-3. (elsevier.com)
- This work stated that anti-androgen activity of curcumin analogs was through S5αR inhibition mechanism and the information might lead to further design of new curcumin analogs with improved potency and safety. (springer.com)
- Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. (pubmedcentralcanada.ca)
- Androgen Receptor Expression. (tylerweitzman.tk)
- It is a synthetic attenuated androgen with relatively few adverse effects. (medscape.com)
- Adverse effects of synthetic androgen treatment? (flashcardmachine.com)
- Adverse effects of synthetic androgen treatment in women and children? (flashcardmachine.com)
- Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. (nih.gov)
- Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. (bcgsc.ca)
- Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. (bcgsc.ca)
- Androgen Antagonists" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
- The mainstay of first-line treatment for patients with metastatic prostate cancer is suppression of gonadal androgens by medical or surgical castration, a strategy that was described 7 decades ago by Charles Huggins and colleagues ( 1 ). (aacrjournals.org)
- These are used along with chemical or surgical castration to remove all chances of exposure of prostate cancer cells to androgens from the adrenal gland, rather than removing the adrenal gland which could result in fatal or debilitating outcomes, such as hypoadrenalism. (news-medical.net)
- Orally active non-steroidal androgen receptor antagonist (IC 50 = 190 nM). (tocris.com)