Compounds which inhibit or antagonize the biosynthesis or actions of 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.
An antiandrogen with about the same potency as cyproterone in rodent and canine species.
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.
An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.
A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.
Tumors or cancer of the PROSTATE.
Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.
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.
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.
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.
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.
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.
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.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
Agents inhibiting the effect of narcotics on the central nervous system.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
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.
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.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
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.
A family of hexahydropyridines.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
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.
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.
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.
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.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
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.
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.
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.
Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
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.
An enzyme that catalyzes the reduction of TESTOSTERONE to 5-ALPHA DIHYDROTESTOSTERONE.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A cell line derived from cultured tumor cells.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.
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.
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 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.
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.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.
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.
Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.
Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
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.
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 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.
Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.
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)
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.
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.
Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.
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)

TY - JOUR. T1 - Risk assessment among prostate cancer patients receiving primary androgen deprivation therapy. AU - Cooperberg, Matthew R.. AU - Hinotsu, Shiro. AU - Namiki, Mikio. AU - Ito, Kazuto. AU - Broering, Jeanette. AU - Carroll, Peter R.. AU - Akaza, Hideyuki. PY - 2009/9/10. Y1 - 2009/9/10. N2 - Purpose: Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients. Methods: Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research ...
The trial follow-up period was stopped early (median follow-up, 6.9 years) because a planned interim analysis, reviewed by an independent data and safety monitoring committee, unequivocally demonstrated no difference in survival outcome between the two treatment groups. Median overall survival was 8.8 years on intermittent androgen suppression vs 9.1 years on continuous androgen deprivation (HR = 1.02; 95% CI = 0.86-1.21; P = .009 for noninferiority [HR ≥ 1.25 for intermittent androgen suppression vs continuous androgen deprivation]). Patients on the intermittent androgen suppression arm had more disease-related deaths (122 vs 97) and fewer disease-unrelated deaths (134 vs 146).. Patients receiving intermittent androgen suppression therapy had a reduced incidence of hot flashes, but rates of other adverse events, including myocardial events and osteoporotic fractures, were similar between the two groups. Full testosterone recovery was noted in 35% of men on the intermittent androgen ...
RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer.. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer. ...
RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer.. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer. ...
Men with advanced prostate cancer had similar survival with intermittent or continuous androgen deprivation therapy, pooled data from two randomized trials showed.
Cancer of the prostate (CaP) is the most frequently diagnosed non-cutaneous malignancy worldwide, and it is the second leading cause of death from cancer in men. In the developing world, majority of patients with CaP present in advanced stage and often times, androgen deprivation therapy (ADT) is the only treatment option available. ADT has been reported to increase the risk of osteopenia and osteoporosis in patients with CaP in studies done predominantly among the Caucasians. There is a dearth of report of the effect of ADT on CaP in the black population most especially Nigerian population despite our high incidence of CaP. The aim of this study was to determine the effect of advanced CaP and its treatment using ADT on bone mineral density (BMD) in our patients. The age of the patients ranged from 54 to 88 years (mean 70.15 ± 6.7) and 50 to 85 years (mean 68.92 ± 8.5) for the case and control groups, respectively. The mean BMD of the control group (0.26 ± 1.5) was significantly higher than the case
Purpose - Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort.. Methods - Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility ...
TY - JOUR. T1 - Combined androgen blockade achieved better oncological outcome in androgen deprivation therapy for prostate cancer. T2 - Analysis of community-based multi-institutional database across Japan using propensity score matching. AU - Onozawa, Mizuki. AU - Akaza, Hideyuki. AU - Hinotsu, Shiro. AU - Oya, Mototsugu. AU - Ogawa, Osamu. AU - Kitamura, Tadaichi. AU - Suzuki, Kazuhiro. AU - Naito, Seiji. AU - Namiki, Mikio. AU - Nishimura, Kazuo. AU - Hirao, Yoshihiko. AU - Tsukamoto, Taiji. N1 - Publisher Copyright: © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.. PY - 2018/10. Y1 - 2018/10. N2 - Background: This study investigated how differences in the method of the first-line androgen deprivation therapy (ADT) affected the time to castration-resistant prostate cancer. Methods: The Japan Study Group of Prostate Cancer compiled a nationwide community-based database on prostate cancer patients who underwent ADT. That database included 13 774 patients who were ...
TY - JOUR. T1 - Androgen-deprivation therapy in prostate cancer: A European expert panel review. AU - Schulman, Claude C.. AU - Irani, Jacques. AU - Morote, Juan. AU - Schalken, Jack A.. AU - Montorsi, Francesco. AU - Chlosta, Piotr L.. AU - Heidenreich, Axel. PY - 2010/1/1. Y1 - 2010/1/1. N2 - Context: Androgen-deprivation therapy (ADT) is the mainstay of treatment for metastatic prostate cancer and is also recommended in association with external-beam radiation therapy (EBRT) for patients with high-risk disease. Objective: Our aim was to make recommendations regarding optimal timing of ADT, target serum testosterone levels, intermittent ADT delivery, and quality of life (QoL) during ADT. Evidence acquisition: This review contains recommendations from a European expert panel held in May 2009. Evidence synthesis: There is ongoing debate over whether ADT should be initiated at diagnosis or delayed until biochemical or symptomatic progression. Immediate ADT is recommended for metastatic disease to ...
TY - JOUR. T1 - Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy. AU - Matsumoto, Kazuhiro. AU - Niwa, Naoya. AU - Hagiwara, Masayuki. AU - Kosaka, Takeo. AU - Takeda, Toshikazu. AU - Yasumizu, Yota. AU - Tanaka, Nobuyuki. AU - Morita, Shinya. AU - Mizuno, Ryuichi. AU - Shinojima, Toshiaki. AU - Hara, Satoshi. AU - Asanuma, Hiroshi. AU - Oya, Mototsugu. N1 - Publisher Copyright: © 2021, Japan Society of Clinical Oncology.. PY - 2021/4. Y1 - 2021/4. N2 - Background: The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). Methods: We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not ...
Phase IIIb Randomized Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer. A Joint Study of t
We know bone-protecting agents can be used to prevent bone loss in men taking androgen-deprivation therapy. Bone-protecting agents can also delay the time to first skeletal-related events in men with metastatic castration-resistant prostate cancer and bone metastasis. There are two different indications with different doses used for men receiving androgen-deprivation therapy and men with metastatic castration-resistant prostate cancer and bone loss, explained Dr. Gillessen.. Background. Osteoporotic fractures are reported in up to 11% of patients treated with androgen-deprivation therapy and an androgen receptor (AR) pathway inhibitor. Skeletal-related events due to osseous metastases are reported in up to 40% of men treated with androgen-deprivation therapy and an AR pathway inhibitor. These skeletal-related events include pathologic bone fracture, spinal cord compression, orthopedic surgery, and palliative radiation.. Osteoporotic fractures in men on androgen-deprivation therapy are probably ...
Health, ...WASHINGTON A study of more than 15000 men with early stage prostate ...The research team led by scientists at Georgetown Lombardi Comprehens...The findings reported Monday in the Journal of Clinical Oncology/...Androgen deprivation therapy suppresses the production of testosterone...,Primary,androgen,deprivation,therapy,ineffective,for,most,men,with,early,prostate,cancer,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
TY - JOUR. T1 - Positive and negative mood in men with advanced prostate cancer undergoing androgen deprivation therapy. T2 - Considering the role of social support and stress. AU - Benedict, Catherine. AU - Dahn, Jason R.. AU - Antoni, Michael H. AU - Traeger, Lara. AU - Kava, Bruce. AU - Bustillo, Natalie. AU - Zhou, Eric S.. AU - Penedo, Frank J.. PY - 2015/8/1. Y1 - 2015/8/1. N2 - Advanced prostate cancer patients often undergo androgen deprivation therapy (ADT). Advanced disease and adverse ADT side effects are often debilitating and negatively impact mood. Social support has been shown to mitigate detrimental effects of stress on mood. Objective This study sought to characterize positive and negative mood in this select patient population and determine whether social support moderated relations between stress and mood. Methods Participants (N=80) completed the Interpersonal Support Evaluation List, Perceived Stress Scale, and Derogatis Affect Balance Scale at a single time point. ...
Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of ,80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. ...
Primary androgen deprivation therapy (PADT) was linked with increased all-cause mortality and prostate cancer-specific mortality.
Purpose Principal androgen-deprivation therapy (PADT) is usually often used to take care of clinically localized prostate cancer, but its effects about cause-specific and general mortality never have been established. prostate-cancerCspecific mortality (HR, 1.03; 95% CI, 0.89 to at least one 1.19) after adjusting for all those sociodemographic and clinical characteristics. PADT was connected with decreased threat of all-cause mortality however, not prostate-cancerCspecific mortality. PADT was connected with decreased threat of all-cause mortality just among 141750-63-2 IC50 the subgroup of males with a higher risk of malignancy development (HR, 0.88; 95% CI, 0.78 to 0.97). Summary We discovered no mortality reap the benefits of PADT weighed against no PADT for some males with medically localized prostate malignancy who didnt receive curative intention therapy. Males with higher-risk disease may derive a little clinical reap the benefits of PADT. Our research provides the greatest available ...
Thromboembolic events are potentially fatal adverse events associated with malignancy as well as androgen deprivation therapy (ADT). In the analysis of the PCBaSe Sweden, the Swedish database that captures 98% of all new prostate cancer diagnoses, the authors compared men with prostate cancer on ADT (anti-androgen = 11,242; GnRH agonist = 26,959; combined blockade = 1091; surgical castration = 3789) with a matched cohort of men without prostate cancer.
PURPOSE To assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular disease mortality (CVDM), or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age. PATIENTS AND METHODS This retrospective population-based cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich. Multiple imputation methods were applied to handle missing PCa information. Fine and Gray competing risk regression analysis was used to estimate subdistribution hazard ratios for the outcomes PCSM, CVDM, or OCM RESULTS: Ten years after diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%, respectively. We observed an increased adjusted risk of PCSM in men treated with androgen deprivation therapy (ADT) compared to surgery, but could not observe an association between ADT and CVDM. The probability of PCSM was ...
1 Introduction Treatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is effective, but can be associated with debilitating side effects. Oligometastasis describes a state of limited metastatic capacity (Weichselbaum 2011). This may represent an intermediate disease state that is amenable to aggressive local therapy, allowing deferral of ADT. In practice oligometastasis usually refers to five or fewer metastases. These early metastatic lesions may seed further metastases. Therefore, eradication of oligometastases may alter the progression of disease and potentially offer cure in select cases. Surgery or radiation therapy are the two treatment options in this setting. Stereotactic body radiotherapy (SBRT) is relatively non-invasive. It delivers an ablative dose of radiotherapy to target tissues, minimising scatter to adjacent structures. Early evidence in other cancers suggests SBRT is a safe and effective treatment for oligometastatic disease (Tree 2013). Conclusions ...
Androgen deprivation therapy remains to be a critical element of treatment for guys with advanced prostate tumor, and data works with its make use of in metastatic disease and together with medical procedures or rays in specific configurations. such as for example abiraterone acetate, are eagerly anticipated. 1: 34C45 ? Macmillan Web publishers Ltd. All privileges reserved. Abbreviations: AR, androgen receptor; ARA70, androgen receptor linked proteins 70; DHT, dihydrotestosterone; GTA, general transcription activation; HSP, heat-shock proteins; SHBG, sex-hormone-binding globulin. Historically, circulating testosterone amounts have been utilized to assess the efficiency of androgen depletion, using a focus on total testosterone level below 50,ng/dl ( 1.74,nmol/l). This focus on is defined based on the degree of suppression attained with operative castration, and continues to be the standard for analyzing the effectiveness of agents such as for example GnRH agonists.11 In men with prostate ...
Evidence-based recommendations on enzalutamide (Xtandi) for treating high-risk hormone-relapsed non-metastatic prostate cancer in adults
CTLA-4 blockade has demonstrated antitumor efficacy in human clinical trials. The antitumor mechanism is presumably mediated in part by the expansion of tumor-specific T cells. Androgen deprivation, t
Some men receiving Androgen Deprivation Therapy (ADT; also called hormone therapy) report a decline in their thinking skills (eg.memory). But some men may experience more of a change than others. This suggests that there may be factors that make some men more, or less, at risk of a drop in thinking skills after ADT than others. These researchers aim to identify these factors so that men can be given evidence based information before making treatment decisions around hormone therapy. Population based studies like this will give us knew information that might help in developing interventions to manage the side-effects of treatment. ...
This is a multi-center phase III study to compare the clinical benefit of androgen deprivation therapy (+ docetaxel) with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer.
Researchers have found an association between androgen deprivation therapy (ADT) for prostate cancer and increased risk for Alzheimers disease…
Background: Prostate cancer (PC) is the most frequent neoplasia in the male population and androgen deprivation therapy (ADT) is frequently used in the management of the disease.Aim: To evaluate the effect of ADT exposure on cognitive status, grey matter volume (GMV) and white matter lesion (WML) load.Methods: Fifty ADT patients and fifteen PC-non-ADT (control) patients were included in the study. A neuropsychological evaluation was performed and a magnetic resonance imaging (MRI), with anatomical T1 and FLAIR sequences, was performed to evaluate the GMV and the WML burden.Results: Most of the patients included in the study presented a significant cognitive impairment (CI). No significant differences were identified in the cognitive assessment between the studied groups, but when considering the educational background intragroup differences were found.No significant difference of GMV and WML volume were identified between groups, but a negative relationship between the ADT period and the GMV was
Immune Responses Enhanced and Sustained When PROVENGE® (sipuleucel-T) is Given After Androgen Deprivation Therapy in Biochemically-Recurrent Prostate Cancer
The paper, titled Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization, shows for the first time that GCP keeps filamin A in the nucleus. As long as this protein remains attached to the androgen receptor, the cancerous cells need androgens to survive and grow. They die off when starved of androgens, thus prolonging the effects of androgen deprivation, which ultimately prolongs the patients life.. The teams hypothesis is that metastatic prostate cancer patients with the weakest response to androgen-deprivation therapy could be given GCP concurrently with androgen deprivation therapy to retain Filamin A in the nucleus, thereby allowing cancer cells to die off. De Vere White is now pursuing funding to begin GCP human clinical trials. Because GCP is a natural product rather than a drug, and requires fewer government approvals, its expected that these trials will proceed rapidly once funded.. We should know within the first eight ...
Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT ...
Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT ...
August 12, 2009 - There are higher rates of both osteoporosis and nonpathologic fractures for men with nonmetastatic prostate cancer using androgen-deprivation therapy (ADT). The role of ADT in men with metastatic prostate cancer - especially patients who receive external beam radiotherapy or who have node-positive disease - has been prospectively established. However, the most common use of ADT in the U.S. is for nonmetastatic prostate-specific antigen failure, for which prospective evidence of benefit is lacking.. Bisphosphonates have been widely used to lower incidence of skeletal events (e.g., pathologic fractures in patients with metastatic disease) and to attenuate development of osteoporosis. However, use of this class of drugs carries a small but real risk for development of renal insufficiency and osteonecrosis. A novel compound that might be used in this setting is denosumab, a human monoclonal antibody that binds to the receptor activator of nuclear factor-B ligand (a key mediator of ...
One of the major treatments for prostate cancer is androgen-deprivation therapy (ADT), and about 50% of prostate cancer patients are treated with ADT at some point in their disease. ADT is used most frequently for patients with local but advanced prostate cancer or metastatic prostate cancer.
At a median follow-up of 29 months, median OS was 44 months in the ADT group versus 57.6 months in the ADT-docetaxel group, or a 39% higher likelihood of survival in the combination arm at any time point during the study (haz-ard ratio 0.61, P = .0003).. Among 520 patients with high-volume disease (visceral metastases and/or 4 or more bone metastases), adding docetaxel to ADT improved median OS by 17 months (32.2 months in the ADT-only group vs 49.2 months in the combi-nation group). The median OS in patients with low-volume disease has not yet been reached.. Combination therapy favored all subgroups. Patients were stratified according to age, volume of disease, bone and vis-ceral metastases, race, Gleason score, prior local therapy, use of anti-androgen therapy beyond 30 days, and skeletal-related events.. Docetaxel also delayed disease progression. At 1 year, the percentage of patients with prostate-specific antigen (PSA) levels less than 0.2 ng/mL was 11.7% in the ADT group versus 22.7% in ...
Purpose: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. Methods and Materials: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15 patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. Results: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES ,3 but choosing the condensed treatment. One man was not treated owing ...
RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. It is not yet known whet
This trial will investigate the efficacy and tolerability of vandetanib [Zactima] in prostate cancer patients undergoing intermittent androgen deprivation
When LAPC patients are treated with RT+ADT, LT-ADT is generally defined as the administration of ADT over 2 years, usually prescribed as an adjuvant. A total of five phase III trials have reported long-term follow-up results from approximately 2,500 patients [4-7,10,12-16] (Table 4). As described previously, the purposes of those five studies were to compare the clinical outcomes of LT-ADT+RT with RT alone (RTOG 8531 and EORTC 22863) [4-7,10], or with ADT alone (NCIC CTG/MRC and SPCG-7/SFUO-3) [12-14] or with ST-ADT (RTOG 9202) [15,16] in LAPC patients. In most studies, the median age was around 70 years but, in SPCG-7/SFUO-3, it was 66 years [14]. RTOG 8531 enrolled a larger proportion of node-positive disease (29%) cases than the others (3%-4%) [4,6,7]. Patients with locally advanced stage (cT3-4) accounted for over 70% of the cohort, except for RTOG 9202 (cT2c 45%, cT3-4 55%). A total dose of 65-70 Gy was delivered to the prostate target (approximately 45-50 Gy of pelvic RT followed by 20-25 ...
Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database.
Primary androgen deprivation therapy (PADT) has played an important role in the treatment of prostate cancer. We sought to identify factors of PSA progression in our series of patients with localized and locally advanced prostate cancer treated with PADT. Six-hundred forty-nine patients with localized and locally advanced prostate cancer who received PADT from 1998 to 2005 by Nara Uro-Oncology Research Group were enrolled. Age, T classification, stage, PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and seminal vesicle involvement (SVI) were adopted as parameters of PSA progression. Coxs proportional hazards model was used to determine the predictive factors for PSA progression. The median follow-up period and the median PSA level at diagnosis were 49 months and 15 ng/mL. The 5-year disease specific survival rate, overall survival rate and PSA progression-free survival (PFS) rate were 97.9 %, 91.9 % and 71.2 %, respectively. The univariate analysis showed that the PSA
Davis M.K., Rajala J.L., Tyldesley S., Pickles T., Virani S.A.. Journal of Oncology 2015 2015 Article Number 820403. Background. While androgen deprivation therapy (ADT) reduces the risk of prostate cancer-specific mortality in high-risk localized prostate cancer, it adversely affects cardiovascular (CV) risk factor profiles in treated men. Methods. We retrospectively reviewed the charts of 100 consecutive men with intermediate- or high-risk localized prostate cancer referred to the British Columbia Cancer Agency for ADT. Data on CV risk factors and disease were collected and Framingham risk scores were calculated. Results. The median age of the study cohort was 73 years. Established cardiovascular disease was present in 25% of patients. Among patients without established CV disease, calculated Framingham risk was high in 65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58% of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in 24%. ...
TY - JOUR. T1 - Exercise medicine to arrest bone loss in men with prostate cancer undergoing androgen deprivation therapy. T2 - 18th Asia-Pacific Prostate Cancer Conference. AU - Newton, Robert U.. AU - Galvao, Daniel A.. AU - Spry, Nigel. AU - Joseph, David. AU - Chambers, Suzanne K.. AU - Gardiner, Robert A.. AU - Hayne, Dickon. AU - Hart, Nicolas H.. AU - Wall, Brad A.. AU - Bolam, Kate A.. AU - Taaffe, Dennis R.. PY - 2017/8. Y1 - 2017/8. M3 - Abstract/Meeting Abstract. VL - 120. SP - 15. EP - 15. JO - British Journal of Urology International. JF - British Journal of Urology International. SN - 1464-410X. Y2 - 30 August 2017 through 2 September 2017. ER - ...
TY - JOUR. T1 - Bone mass behavior after 1 year of different treatment strategies in prostate cancer patients subjected to androgen deprivation therapy. AU - Planas Morin, J.. AU - Celma Domenech, A.. AU - Placer Santos, J.. AU - Trilla Herrera, E.. AU - Salvador Lacambra, C.. AU - Lorente Garcia, D.. AU - Regis, L.. AU - Carles Galceran, J.. AU - Morote Robles, J.. PY - 2014/1/1. Y1 - 2014/1/1. N2 - © 2014, Springer-Verlag Berlin Heidelberg. The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray ...
Purpose: Prostate cancer survivors (PCS) on androgen deprivation therapy (ADT) experience adverse side effects such as skeletal muscle loss and adiposity gain, together called sarcopenic obesity, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance exercise can increase skeletal muscle mass, but no exercise interventions to date in PCS on ADT have concomitantly improved sarcopenic obesity and cardiometabolic risk factors. Utilizing a 12-week intervention of progressive resistance exercise designed to target skeletal muscle mass, this ongoing pilot trial investigates sarcopenic obesity and as a secondary analyses, MetS components, in PCS on ADT.. Methods: Eighteen PCS (65.6±8.8 yr) on current or previous ADT were recruited from the USC Norris Comprehensive Cancer Center and randomized to resistance training (RT; n=9) or a control stretching program (CS; n=9). Body composition, measured through dual-x-ray absorptiometry, and MetS outcomes, including ...
U.S., Jan. 30 -- ClinicalTrials.gov registry received information related to the study (NCT03031821) titled Metformin in Patients Initiating ADT as Prevention and Intervention of Metabolic Syndrome on Jan. 20. Brief Summary: This is a multi-centre, double-blind, randomized phase III trial comparing metformin to placebo in patients with advanced prostate cancer starting intermittent androgen deprivation therapy. Study Start Date: Study Type: Interventional Condition: Prostate Cancer Metabolic Syndrome Intervention: Drug: Metformin Metformin Duration: 18 months 850 mg PO OD x 30 days then 850 mg PO BID for duration Other Name: Glucophage Drug: Placebo Oral Tablet Placebo Oral Tablet Duration 18 months 1 tablet (850 mg) PO OD x 30 days then 1 tablet PO BID for duration Other Name: Placebo Recruitment Status: Not yet recruiting Sponsor: British Columbia Cancer Agency Information provided by (Responsible Party): British Columbia Cancer Agency ...
A combination regimen plus androgen-deprivation therapy prolongs overall survival (OS) and radiographic progression-free survival (PFS) in newly diagnosed patients with metastatic, castration-sensitive prostate cancer, according to a recent study published in the New England Journal of Medicine (July 27, 2017;377:352-360).. -----. Related Content. Metastatic Hormone-Naïve Prostate Cancer Effectively Treated With Combination Therapy. Lower Dosage of Prostate Cancer Drug Equally Effective When Taken With Low-Fat Meal. -----. Abiraterone acetate in combination with prednisone has demonstrated effectiveness in patients with metastatic, castration-resistant prostate cancer who have not received prior chemotherapy or in those who have received previous docetaxel. Including androgen-deprivation therapy in this regimen has been shown to reduce tumor burden in men with high-risk, localized prostate cancer who are receiving neoadjuvant therapy.. Karim Fizazi, MD, PhD, and colleagues conducted a study to ...
Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in U.S. men. While tumors initially respond to androgen-deprivation therapy, the standard care for advanced or metastatic disease, tumors eventually recur as castration-resistant prostate cancer. Upregulation of the insulin-like growth factor signaling axis drives growth and progression of prostate cancer by promoting proliferation, survival, and angiogenesis. Ganitumab (formerly AMG 479) is a fully human antibody that inhibits binding of IGF-1 and IGF-2 to IGF-1R. Ganitumab decreased IGF-1 induced phosphorylation of the downstream effector AKT and reduced proliferation of multiple androgen-dependent and castration-resistant human prostate cancer cell lines in vitro albeit to varying extents. We evaluated the therapeutic value of ganitumab in several pre-clinical settings including androgen-dependent prostate cancer, castration-resistant (recurrent) prostate cancer, and in combination with androgen-deprivation therapy.
Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical Activity after Diagnosis and Risk of Prostate Cancer Progression: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor. Cancer Res. 2011 May 24;71(11):3889-95. • Rosario DJ, Lane JA, Metcalfe C, Donovan JL, Doble A, Goodwin L, et al. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ. 2012;344:d7894 ...
Clinical Scenario. A 77-year-old man presents to his primary care physician for evaluation after a single episode of rectal bleeding, which is found to be related to his known history of hemorrhoids. At the time of examination, he is found to have a firm prostate with prominent bilateral nodularity. Due to suspicion for prostate cancer, a prostate-specific antigen (PSA) test is given, which returns at 16.2 ng/mL. He then undergoes transrectal ultrasound-guided biopsy and is found to have Gleason score 4 + 4 disease in 8 of 12 cores, with 30% to 80% involvement of each core. Staging reveals no evidence for skeletal metastasis, but shows a single enlarged right internal iliac lymph node. The patient has good urinary and sexual function, and is otherwise in excellent health. After obtaining his diagnosis of high-risk prostate cancer (cT2c, Gleason score 4+4, PSA 16.2), he consults a physician who recommends androgen-deprivation therapy (ADT) alone. He presents to you seeking a second opinion, with ...
Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored ...
Longer Duration of Androgen Deprivation Therapy Increases Risk of Depression in Early Prostate Cancer (04-25-2016) Among men with early prostate cancer, the risk of depression is increased with the use of androgen-deprivation therapy (ADT), particularly among men who are treated with ADT for 12 months or longer. It is important for patients receiving ADT to speak... Continue Reading. ...
Kristine Lacuna, Class of 2018. Androgen Deprivation Therapy With or Without Docetaxel for Men With Non-Metastatic, Castration Sensitive Prostate Cancer Who Biochemically Relapse After Prostatectomy (TAX3503): A Randomized, Open-Label, Phase 3 Trial. The optimal treatment of patients with non-metastatic, castration sensitive prostate cancer (CSPC) who biochemically relapse following a radical prostatectomy (RP) is unknown.. Lacunas study examined the effects of adding docetaxel to androgen deprivation therapy (ADT) in non-metastatic CSPC patients.. The study concluded the clinical benefit of adding docetaxel to ADT in non-metastatic CSPC patients with biochemical recurrence following an RP appears to be marginal. However, there is a statistical trend toward improved progression-free survival.. Mentors/collaborators: Ilyse Acosta, Andrew J. Armstrong, MD; Michael Anthony Carducci, MD; Erica Simone Dayan, Julie Filipenko, Martin Edwin Gleave, MD; Glenn Heller, PhD; Patrick Hilden, Michael J. ...
Red and processed meat may increase risk of advanced prostate cancer. Data on postdiagnostic diet and prostate cancer are sparse, but postdiagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g., men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994 to 2008. We also conducted a case-only survival analysis to examine postdiagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with nonmetastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared with men who consumed less than 0.5 eggs per week (HR: ...
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Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P , 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P , 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P , 0.0001). Increased serum calcium (P , 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P , 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P , 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. ...
The purpose of this study is to determine the safety and efficacy of a short course of radiotherapy (40Gy/5 fractions/29 days) for the treatment of high
Androgen deprivation therapy, one of the standard treatments for prostate cancer, induces apoptosis as well as autophagy in androgen-responsive PCa cells. As modulation of autophagy is a new paradigm for enhancing the therapeutic efficacy of various cancer therapies, we sought to determine the functions of autophagy during androgen deprivation. In this study, we confirmed that androgen removal or inhibition induces autophagy in two different hormone sensitive prostate cancer cells. Androgen deprivation also caused depletion of lipid droplets which was abrogated on inhibition of autophagy by pharmacological means (3-methyladenine, bafilomycin A1) or using a genetic approach (Atg5 siRNA). In addition, colocalization of lipid droplets and autophagic vesicles was observed in LNCaP cells, which was further enhanced by blocking the autophagic flux. These findings suggest that autophagy mediates lipid droplet degradation and lipolysis in androgen sensitive prostate cancer cells. Furthermore, inhibition of
Prostate cancer often develops antiandrogen resistance, possibly via androgen receptor (AR) mutations, which change antagonists to agonists. Novel therapies with increased anticancer activity, while overcoming current drug resistance are urgently needed. Enobosarm has anabolic effects on muscle and bone while having no effect on the prostate. Here, we describe the activity of novel chemically modified enobosarm analogues. The rational addition of bis‐trifluoromethyl groups into ring B of enobosarm, profoundly modified their activity, pharmacokinetic and tissue distribution profiles. These chemical structural modifications resulted in an improved AR binding affinity-by increasing the molecular occupational volume near helix 12 of AR. In vitro, the analogues SK33 and SK51 showed very potent antiandrogenic activity, monitored using LNCaP/AR‐Luciferase cells where growth, PSA and luciferase activity were used as AR activity measurements. These compounds were 10-fold more potent than bicalutamide ...
Use of androgen suppression therapy may negatively impact survival in African American patients with favorable-risk prostate cancer.
Darolutamide was approved in the U.S. under the FDA Priority Review designation; approval granted three months ahead of target FDA action date / Approval based on Phase III ARAMIS trial evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT
A new analysis has found that men diagnosed with nonmetastatic prostate cancer who consumed more than 140 μg a day of supplemental selenium had over a two-and-a-half-fold excess risk for death from prostate cancer compared with nonsupplement users. On the other hand, there was a modest 12% inverse association between selenium supplementation and the risk […]. ...
BACKGROUND: Metastatic prostate cancer is a clonally heterogeneous disease state characterized by progressive somatic perturbations. The aim of this study was to identify cell free DNA- (cfDNA-) based alterations and their associations with outcomes in progressive metastatic prostate cancer. METHODS: In this longitudinal prospective cohort study plasma cfDNA/circulating tumor DNA (ctDNA) was analyzed before, during, and after androgen deprivation therapy (ADT) in 4 independent patient groups ranging from untreated metastatic hormone sensitive prostate cancer (mHSPC) to metastatic castrate resistant prostate cancer (mCRPC). Next generation sequencing was performed on ctDNA and germline DNA to characterize alterations and associations with clinical outcomes were determined for each group. FINDINGS: cfDNA yields were different in progressive mHSPC and mCRPC states (P | .001). In mHSPC, a higher than median ctDNA fraction was predictive of shorter time to ADT failure (HR, 2.29 [95% CI, 1.13-4.65]; Log-Rank
Androgen deprivation therapy (ADT) is highly effective therapy for men with advanced or metastatic prostate cancer, providing at least temporary disease control in over 80 percent of cases. However, the vast majority eventually develop progressive di
In men with de novo metastatic castration-sensitive prostate cancer treated in the phase 3 PEACE-1 study, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy and docetaxel improved radiographic progression-free surviva.
Androgen deprivation therapy (ADT) is a common treatment option for patients with advanced stage prostate cancer. But nearly 80 percent of patients who receive ADT report experiencing hot flashes during and after treatment. Moffitt Cancer Center researchers are working to determine what genetic factors and other characteristics might make prostate cancer patients more likely to experience hot flashes during and after therapy.
Results from the second interim analysis of the Phase 3 SPARTAN study featured in an oral presentation at ESMO 2019 and simultaneously published in Annals of Oncology BARCELONA, Spain, Sept. 27, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced today updated, longer-term results from the pivotal Phase 3 SPARTAN study following a second interim analysis. Treatment with ERLEADA® (apalutamide) plus androgen deprivation therapy (ADT) resulted in a 25 percent reduction in the risk of death compared with placebo plus ADT in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were at high risk of developing metastases.1 The updated findings showed overall survival (OS) results supported the first interim analysis, despite a crossover of patients receiving placebo to the ERLEADA® treatment group.1 Results were presented in an oral session at the 2019 European Society for Medical Oncology (ESMO) Annual Congress (abstract #843O), and
This trial is comparing the efficacy and tolerability of neo-adjuvant docetaxel + androgen deprivation comprising leuprorelin + goserelin + radical
Several men with metastatic, hormone-sensitive prostate cancer live longer on constant androgen-deprivation therapy, (hormone therapy), than intermittent therapy, states a study led by SWOG.
Despite current risk stratification systems using traditional clinicopathologic factors, many localized and locally advanced prostate cancers fail radical treatment (ie, radical prostatectomy, radiation therapy with or without androgen deprivation therapy). Therefore, a pressing need exists for enhanced methods of
Background: Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer (PCa); however, it accelerates the loss of bone mineral density (BMD), which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to assess baseline fracture risk properly. The objective of this study was to examine the proportion of BMD testing in men initiating ADT in Quebec and to identify factors associated with receipt of this testing. Methods: The study cohort consisted of men extracted from Quebec public healthcare insurance administrative databases who initiated continuous ADT from 2000 to 2015 for ,12 months. The primary study outcome was receipt of BMD testing in the period from 6 months before through 12 months after ADT initiation. Multivariable generalized linear mixed regression modeling with a logit link was performed to identify variables associated with BMD testing. Results: We identified 22,033 patients, of whom 3,910 (17.8%) underwent BMD testing. ...
Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to patient with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of survival. The GETUG-AFU-15 and CHAARTED studies assessed the effi cacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in patients with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (~75%) and patients with metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUGAFU- 15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT ...
A prescription of short-term exercise for patients with advanced prostate cancer would help to reduce the side effects of hormone therapy, according to new research.. Researchers from the Norfolk and Norwich University Hospital (NNUH) and University of East Anglia (UEA) led a trial which involved patients who were due to start androgen deprivation therapy (ADT).. Fifty patients took part in the research study, with half of the participants taking part in two supervised exercise sessions a week for three months at specialist exercise science facilities at UEA.. The trial aimed to reduce the adverse side effects of hormone therapy such as weight gain and an increased risk of heart problems and assessed participants health three months after their exercise programme.. The findings, which have been published in the British Journal of Urology International (BJUI), showed that the three month programme of aerobic and resistance training intervention prevented adverse changes in cardiopulmonary ...
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Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. Data from ten trials published from
Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., Astellas) and Pfizer Inc. (NYSE: PFE) announced today results of the final overall survival (OS) analysis from the Phase 3 PROSPER trial, which evaluated XTANDI® (enzalutamide) plus androgen deprivation therapy (ADT
Group-based exercise in daily clinical practice to improve physical fitness in men with prostate cancer undergoing androgen deprivation therapy: study protocol ...
(PRWEB) August 22, 2017 -- It is well known that men who receive androgen deprivation therapy (ADT) after diagnosis of prostate cancer can experience
There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease.To examine the efficacy of any form of LT±androgen deprivation therapy (ADT) in treating these individuals.
Prostatic adenocarcinoma (PCa) is the most frequently diagnosed non-cutaneous malignancy and second leading cause of cancer death in men in the US. Although organ-confined disease is manageable, treatment options for disseminated PCa are limited. First-line therapy for metastatic PCa targets the androgen receptor (AR) via androgen deprivation therapy (ADT); however, tumors often recur, displaying reactivation of AR signaling despite continued therapeutic targeting. There is currently no durable treatment for this advanced disease stage, termed castrate-resistant PCa (CRPC). While most localized PCa express wild-type p53, recent high-profile, genome-wide studies identified increased TP53 gene mutation rates in advanced disease (specifically CRPC). Using these data, we noted that the patient-derived, CRPC-specific p53 mutations observed are relatively unique to prostate cancer. These mutations occur in hotspot clusters altered in other tumor types, but represent distinct amino acid changes ...
Newswise - PHILADELPHIA-A common hormone therapy to treat prostate cancer may double a mans risk of dementia, regardless of his age, Penn Medicine researchers reported in a study published online today in JAMA Oncology.. Last year, researchers discovered a dramatic association between Alzheimers disease and androgen deprivation therapy (ADT), a mainstay of treatment for prostate cancer since the 1940s currently used in over a half million men in the United States. This new study suggests a broader neurocognitive risk associated with the testosterone-lowering therapy.. While the findings do not prove that ADT increases the risk of dementia, the analysis comparing the medical records of almost 9,500 prostate cancer patients who received ADT vs. those who did not strongly supports that possibility.. This is not an academic question anymore; this is really a clinical question that needs to be answered, said lead author Kevin T. Nead, MD, MPhil, a resident in the department of Radiation Oncology ...
... 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 ...
... is an antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as ... Clascoterone is a steroidal antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such ... Lerner LJ (1975). "Androgen antagonists". Pharmacol Ther B. 1 (2): 217-31. doi:10.1016/0306-039x(75)90006-9. PMID 772705. "Drug ... is an Androgen Receptor Antagonist in Dermal Papilla Cells In Vitro". J Drugs Dermatol. 18 (2): 197-201. PMID 30811143. Rosette ...
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 B. 1 (2): 217-231. doi:10.1016/0306-039X(75) ... It was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and ...
... is an antiandrogen, or an antagonist of the androgen receptor (AR), the biological target of the androgen sex ... ISBN 978-3-642-80859-3. Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues ... Thus we are left with CPA as the only anti-androgen that is already on the market in several countries. J. Elks (14 November ... ISBN 978-0-87489-225-3. Limited clinical experience also exists with benorterone, the first anti-androgen tried in man, and ...
"Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3): 367-400. doi:10.1016/0163-7258(84)90010-x. PMID ... It is a selective antagonist of the androgen receptor and consequently has progonadotropic effects by increasing gonadotropin ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... Thomson, D. S. (1989). "Pharmacology of Anti-androgens in the Skin". Pharmacology of the Skin II. Handbook of Experimental ...
Ran F, Xing H, Liu Y, Zhang D, Li P, Zhao G (2015). "Recent Developments in Androgen Receptor Antagonists". Archiv der ... 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 ... ISBN 978-1-60761-471-5. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... An over-the-counter histamine H2 receptor antagonist that also shows very weak activity as an AR antagonist. Also inhibits ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... In addition, although CPA reduces androgen production in the gonads, it can increase the production of adrenal androgens, in ... The use of CPA in men has been associated with cellulite, which has been attributed to androgen deficiency as well. CPA has ... Similar depressive changes have been observed with castration, and may be a consequence of androgen deprivation in men. In ...
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 ... There are many different androgen blockers used for transition care. Spironolactone, an aldosterone receptor antagonist, is ... ISBN 978-1-60761-471-5. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ...
"Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211-47. doi:10.2174/ ... It shows 163% of the affinity of testosterone for the androgen receptor and negligible affinity for other steroid hormone ... synthesis and biological profile of high-affinity ligands for the androgen receptor". J. Steroid Biochem. Mol. Biol. 48 (1): ...
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 ...
CPA is a potent competitive antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone ... It has been said that in combined androgen blockade regimens with castration and CPA as the AR antagonist for prostate cancer, ... Androgens: Pharmacodynamics and antagonists. Biochemical and biological studies with 4-aza-steroidal 5 alpha-reductase ... ISBN 978-1-4496-8695-6. Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): ...
Antiandrogens that directly block the androgen receptor are known as androgen receptor antagonists or blockers, while ... nonsteroidal antiandrogens are highly selective for the androgen receptor and act as pure androgen receptor antagonists. ... It works as an antiandrogen mainly by acting as an androgen receptor antagonist. The medication is also a weak steroidogenesis ... In addition to its actions as an antigonadotropin, cyproterone acetate is an androgen receptor antagonist. However, this action ...
Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen ... ISBN 978-1-4831-4566-2. R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 [44], is a powerful ... Takeda AN, Pinon GM, Bens M, Fagart J, Rafestin-Oblin ME, Vandewalle A (2007). "The synthetic androgen methyltrienolone (r1881 ...
... 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 ... Kemppainen JA, Wilson EM (July 1996). "Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen ... 11-. ISBN 978-981-256-920-2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ...
The medication is a silent antagonist of the androgen receptor. RU-56187 is 3- to 10-fold more potent as an antiandrogen than ... RU-57073 RU-58642 RU-59063 Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): ... "Distinguishing androgen receptor agonists and antagonists: distinct mechanisms of activation by medroxyprogesterone acetate and ... It shows 92% of the affinity of testosterone for the androgen receptor and negligible affinity for other steroid hormone ...
Kemppainen JA, Wilson EM (July 1996). "Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen ... 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 ...
Kemppainen JA, Wilson EM (July 1996). "Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen ... Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... a steroidal androgen receptor antagonist". J. Steroid Biochem. 33 (6): 1133-8. doi:10.1016/0022-4731(89)90420-2. PMID 2615358. ... Differential effects on high-androgen responder and low-androgen responder muscle groups". Endocrinology. 154 (12): 4594-606. ...
Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP (July 2002). "Bicalutamide functions as an androgen receptor antagonist by ... Kawahara T, Minamoto H (2014). "Androgen Receptor Antagonists in the Treatment of Prostate Cancer". Clinical Immunology, ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... It works by blocking the androgen receptor (AR), the biological target of the androgen sex hormones testosterone and ...
53-. ISBN 978-3-642-88429-0. Jost A (1971). "Use of androgen antagonists and antiandrogens in studies on sex differentiation". ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... These conditions are worsened by the presence of androgens, and by suppressing androgen levels and blocking their actions, CPA ... Chemical Control of Androgen Action. Annual Reports in Medicinal Chemistry. 21. pp. 179-188. doi:10.1016/S0065-7743(08)61128-8 ...
ISBN 978-3-527-30247-5. Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): ...
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 ... Eunuchs, owing to their low androgen levels and small sebaceous glands, do not develop seborrheic dermatitis. In addition to ... 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 SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... Rosterolone is a derivative of mesterolone, which, in contrast, is an androgen and anabolic steroid. Steroidal antiandrogen ...
Non-steroidal selective androgen receptor antagonists, developed as a treatment for androgen-sensitive prostate cancer, are ... Enzalutamide is an antiandrogen, and acts as an antagonist of the androgen receptor, the biological target of androgens like ... Enzalutamide 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): ...
... is an antiandrogen, and acts as an antagonist of the androgen receptor, the biological target of androgens like ... Apalutamide acts as a selective competitive silent antagonist of the androgen receptor (AR), via the ligand-binding domain, and ... Kawahara, Takashi; Miyamoto, Hiroshi (2014). "Androgen Receptor Antagonists in the Treatment of Prostate Cancer". Clinical ... "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): 43-9. doi:10.1097/PPO. ...
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". ...
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 ... "Androgen Physiology, Pharmacology and Abuse". PMID 25905231.. *^ Kenneth L. Becker (2001). Principles and Practice of ... In accordance with the involvement of androgens in seborrhoea, antiandrogens, such as cyproterone acetate,[27] spironolactone,[ ...
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) ...
Flutamide, a pure antagonist of the androgen receptor, is effective in treating acne in women.[112][120] It appears to reduce ... a pure androgen receptor antagonist with the same mechanism as flutamide and with comparable or superior antiandrogenic ... Both androgens and IGF-1 seem to be essential for acne to occur, as acne does not develop in individuals with complete androgen ... Rasmusson GH (1986). Chemical Control of Androgen Action. Annual Reports in Medicinal Chemistry. 21. pp. 179-188. doi:10.1016/ ...
List of androgen esters § Trenbolone esters. References[edit]. *^ a b c d William Llewellyn (2011). Anabolics. Molecular ... GnRH antagonists (e.g., cetrorelix). *Progestogens (incl., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone ... Androgen receptor modulators. Estrogens and antiestrogens. Progestogens and antiprogestogens. List of androgens/anabolic ... Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ...
GnRH antagonists (e.g., cetrorelix). *Progestogens (incl., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone ... Soon after they differentiate, Leydig cells begin to produce androgens.. Androgen effects[edit]. The androgens function as ... This article is about androgens as natural hormones. For androgens as medications, see Anabolic steroid and Androgen ... Exogenous androgen supplements can be used as a male contraceptive. Elevated androgen levels caused by use of androgen ...
Androgen receptor antagonistsEdit. Androgens and anti-. androgens at the AR[82][83]. Compound. RBA (%). ... Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like ... N-Terminal domain antagonistsEdit. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all currently ... androgen synthesis inhibitors, and antigonadotropins.[5] AR antagonists work by directly blocking the effects of androgens, ...
GnRH antagonists (e.g., cetrorelix). *Progestogens (e.g., chlormadinone acetate, cyproterone acetate, gestonorone caproate, ... Certain androgens/anabolic steroids (e.g., testosterone, testosterone esters, methyltestosterone, metandienone, nandrolone ... Androgens/anabolic steroids (e.g., testosterone, testosterone esters, nandrolone esters, oxandrolone, fluoxymesterone) ... D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ...
Sex steroid antagonists (via disinhibition of the HPG axis): Antiandrogens (e.g., flutamide, bicalutamide, enzalutamide) ... Sex steroid agonists (via negative feedback on the HPG axis): Androgens/anabolic steroids (e.g., testosterone, nandrolone ... Usage of GnRH agonist for this purpose necessitates using a GnRH antagonist instead of a GnRH agonist for suppression of ... D2 receptor antagonists (prolactin releasers) (incl., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ...
What is more clear is that DDE is a weak androgen receptor antagonist and can produce male genital tract abnormalities.[16][17] ... Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ...
Leukotriene antagonists For endocrine problemsEdit. androgens, antiandrogens, estrogens, gonadotropin, corticosteroids, human ... dopamine antagonists, antihistamines, cholinergics, anticholinergics, emetics, cannabinoids, and 5-HT (serotonin) antagonists. ...
Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen ... Bishayee K, Khuda-Bukhsh AR (September 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer ... The paradox is that androgens inhibit the proliferation of these androgen-independent prostate cancer cells.[191][192][193] ... These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen ...
Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... Antagonists. *Steroidal: 7α-Thioprogesterone. *7α-Thiospironolactone. *7α-Thiomethylspironolactone. *11α-Hydroxyprogesterone ... "Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy" (PDF). Nature. 533 (7604): 547-51. doi ...
In complete androgen insensitivity syndrome, a condition in which the AR is defective and insensitive to androgens, there is ... knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen ... Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been ... Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group, above-average sized ...
... primarily estrogens for breast cancer and androgens for prostate cancer) is known as hormonal therapy, while the inhibition of ... Receptor antagonists. *ERA (Atrasentan). *Retinoid X receptor (Bexarotene). *Sex steroid (Testolactone). Other/ungrouped. * ...
Antagonists. *Mifepristone. See also. Receptor/signaling modulators. Progestogens and antiprogestogens. Androgen receptor ...
Androgen receptor modulators. Progesterone receptor modulators. List of estrogens. This drug article relating to the genito- ... Antagonists. *(R,R)-THC. *7β-Hydroxy-DHEA. *Chloroindazole. *Cytestrol acetate. *EM-800 ...
Steroids: Sex steroids: Androgens (AR). *Estrogens (ER). *Progestogens (PR); Corticosteroids: Glucocorticoids (GR) ... Antagonists: 20-Carboxy-LTB4. *Amelubant. *CGS-23131 (LY-223982). *CGS-25019C ...
Caplea A, Seachrist D, Dunphy G, Ely D (April 2001). "Sodium-induced rise in blood pressure is suppressed by androgen receptor ... Currently, the RAS is targeted pharmacologically by ACE inhibitors and angiotensin II receptor antagonists, also known as ... angiotensin receptor blockers (ARBs). The aldosterone system is directly targeted by spironolactone, an aldosterone antagonist ...
Androgen receptor modulators. Estrogens and antiestrogens. Progestogens and antiprogestogens. List of androgens/anabolic ... GnRH antagonists (e.g., cetrorelix). *Progestogens (e.g., chlormadinone acetate, cyproterone acetate, gestonorone caproate, ... Morley JE, Perry HM (May 2003). "Androgens and women at the menopause and beyond". J. Gerontol. A Biol. Sci. Med. Sci. 58 (5): ... Certain androgens/anabolic steroids (e.g., testosterone, testosterone esters, methyltestosterone, metandienone, nandrolone ...
Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... Parthasarathy HK, MacDonald TM (2007). "Mineralocorticoid receptor antagonists". Curr. Hypertens. Rep. 9 (1): 45-52. PMID ... 7α-TS and 7α-TMS have been found to possess approximately equivalent affinity for the rat ventral prostate androgen receptor ( ... Cutler GB, Pita JC, Rifka SM, Menard RH, Sauer MA, Loriaux DL (1978). "SC 25152: A potent mineralocorticoid antagonist with ...
GnRH antagonist. *GnRH agonist (inducing an initial stimulation (flare up) followed by permanent blockage of the GnRH pituitary ... LH supports theca cells in the ovaries that provide androgens and hormonal precursors for estradiol production. At the time of ... Gonadal steroids (estrogens and androgens) generally have negative feedback effects on GnRH-1 release at the level of the ... In both males and females, LH works upon endocrine cells in the gonads to produce androgens. ...
It suppresses gonadal androgen production and hence circulating androgen levels due to its antigonadotropic effects; it ... DES has been identified as an antagonist of all three isotypes of the estrogen-related receptors (ERRs), the ERRα, ERRβ, and ... Oral DES at 0.25 to 0.5 mg/day is effective in the treatment of hot flashes in men undergoing androgen deprivation therapy for ... In 1960, DES was found to be more effective than androgens in the treatment of advanced breast cancer in postmenopausal women.[ ...
Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... Antagonists. *Steroidal: 7α-Thioprogesterone. *7α-Thiospironolactone. *7α-Thiomethylspironolactone. *11α-Hydroxyprogesterone ... See also: List of androgens/anabolic steroids and List of androgen esters ... Androgens. (C-19: Androstane). 1. Dehydroepiandrosterone → Androstenedione → 5α-Androstanedione1 → Androsterone1. 2. ...
Maternal use of androgens or high doses of certain weakly androgenic synthetic progestogens (progestins) structurally related ... ISBN 0-07-142280-3. Schardein, James L. (2000). "Hormones and Hormone Antagonists". Chemically Induced Birth Defects (3rd ed ... The first drugs reported to cause fetal masculinization were the androgens methandriol and methyltestosterone in the mid 1950s ... On June 21, 1976, the FDA approved the androgen danazol (Danocrine), a derivative of ethisterone (17α-ethinyl-testosterone), ...
Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, PXR and CAR agonists and antagonists for treatment of liver ...
Androgen receptor modulators. Estrogens and antiestrogens. Progestogens and antiprogestogens. List of androgens/anabolic ... Raynaud JP, Ojasoo T (1986). "The design and use of sex-steroid antagonists". J. Steroid Biochem. 25 (5B): 811-33. doi:10.1016/ ... Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... Norethisterone is a potent progestogen and a weak androgen and estrogen.[4] That is, it is a potent agonist of the progesterone ...
An effect of natural menopause on circulating androgen levels has not been observed.[54] Thus specific tissue effects of ... Raloxifene exhibits oestrogen agonist activity on bone and lipids, and antagonist activity on breast and the endometrium.[79] ... that act selectively as agonists or antagonists on the estrogen receptors throughout the body. The most commonly prescribed ... "Ovarian androgen production in postmenopausal women". The Journal of Clinical Endocrinology and Metabolism. 92 (8): 3040-3. ...
... and mineralocorticoid antagonists. RAAS inhibition has been proven to be the most effective therapy to slow the progression of ... Androgen receptor (Androgen insensitivity syndrome). *general: Hypogonadism (Delayed puberty). *Hypergonadism *Precocious ...
Androgen receptor modulators. Estrogens and antiestrogens. Progestogens and antiprogestogens. List of androgens/anabolic ... GnRH antagonists (e.g., cetrorelix). *Progestogens (incl., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone ... Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ...
CCL18 has been identified as an endogenous antagonist of the GPER.[16] ... "In vivo effects of a GPR30 antagonist". Nat. Chem. Biol. 5 (6): 421-7. doi:10.1038/nchembio.168. PMC 2864230. PMID 19430488 ...
Androgens and antiandrogens. Estrogen receptor modulators. Progesterone receptor modulators. List of androgens/anabolic ... Antagonists. *Steroidal: 7α-Thioprogesterone. *7α-Thiospironolactone. *7α-Thiomethylspironolactone. *11α-Hydroxyprogesterone ...
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 ...
"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". ...
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 ...
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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 (TOK-001) is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, ... Bicalutamide (ICI-176334) is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. Bicalutamide ... Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is shown to ... Darolutamide (ODM-201, BAY-1841788) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki ...
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, ...
... 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 ...
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 ...
... 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. ...
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 ...
Drug safety is a barrier to the discovery and development of new androgen receptor antagonists. Prostate 71, 480-488 (2011).. ... Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse ... Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse ... Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse ...
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- ...
Phase IIIb Randomized Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH ... The minimum duration of androgen deprivation with GnRH agonist or antagonist therapy is 18 months.. For each patient, the ... PEGASUS Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus ... A non-steroidal anti-androgen (e. g. flutamide, bicalutamide) will be given orally one week before the first injection of the ...
... antagonist, with antineoplastic activity. (R)-Bicalutamide is widely used for the research of prostate cancer. - Mechanism of ... R)-Bicalutamide is the (R)-enantiomer of Bicalutamide (HY-14249). (R)-Bicalutamide is an androgen receptor (AR) ... R)-Bicalutamide is the (R)-enantiomer of Bicalutamide (HY-14249). (R)-Bicalutamide is an androgen receptor (AR) antagonist, ... R)-Bicalutamide is the (R)-enantiomer of Bicalutamide (HY-14249). (R)-Bicalutamide is an androgen receptor (AR) antagonist, ...
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 ...
... steroidal androgen receptor antagonists (like the androgens themselves)andnon-steroidal androgen receptor antagon... ... The androgen receptor antagonists are divided between:. *steroidal androgen receptor antagonists (like the androgens themselves ... Non-steroidal androgen receptor antagonists: The non-steroidal androgen receptor antagonists have common structural elements ... The second generation androgen receptor antagonists (enzalutamide and apalutamide) have the highest affinity to the androgen ...
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 ...
  • Recent studies show that AR antagonists (including the clinically used drug bicalutamide) can enhance AR recruitment of corepressor proteins [nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid receptors (SMRT)] and that loss of corepressors may enhance agonist activity and be a mechanism of antagonist failure. (aacrjournals.org)
  • This androgen antagonistic activity is receptor specific and does not inhibit the closely related glucocorticoid or progesterone receptors . (curehunter.com)
  • Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). (pharmacycode.com)
  • Especialidad en Medicina Interna por el Hospital Universitario Dr.. catecholamines are powerful stimulators of vascular smooth muscle hypertrophy, acting via a1 receptors. (tylerweitzman.tk)
  • Antiandrogens bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone. (medscape.com)
  • Androgen Receptors Downregulate? (anabolicminds.com)
  • I started out with this article planning on giving some textbook style explanation as to why using steroids doesn t down regulate androgen receptors (AR). (anabolicminds.com)
  • Androgen receptors down-regulate .Don t they? (anabolicminds.com)
  • One misunderstood principle of steroid physiology is the concept of androgen receptors (AR), sometimes called 'steroid receptors', and the effects of steroid use on their regulation. (anabolicminds.com)
  • Androgen receptors and adrenergic receptors are quite different. (anabolicminds.com)
  • I feel that once you consider all of the effects of testosterone on muscle cells you come to realize that when you eventually stop growing (or grow more slowly) it is not because there is a reduction in the number of androgen receptors. (anabolicminds.com)
  • They act as competitive antagonists at the GnRH receptors in the anterior pituitary. (flashcardmachine.com)
  • Antiandrogens are a group of medications which bind to intracellular androgen receptors (AR) to prevent androgen effects on organs such as the testes, the hair follicles, the hypothalamus, pituitary, ovaries and the prostate gland, which are targets of endogenous androgens. (news-medical.net)
  • In fact, when too many androgen receptors are present, he said, current antiandrogen drugs begin to stimulate cancer growth. (medpagetoday.com)
  • Bisphenol A (BPA) or its analogs can bind both estrogen receptors (ESR1 and ESR2) and estrogen-related receptors (ERR1-3), which blocks LC gene expression, binds to androgen receptor (NR3C4) as an antagonist to block the activation of LC genes. (frontiersin.org)
  • The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. (pubmedcentralcanada.ca)
  • 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)
  • Promising results for cancer immunotherapy in the clinic have led to attempts to combine immunotherapy with standard-of-care therapies, such as androgen deprivation therapy (ADT) for prostate cancer. (sciencemag.org)
  • Surgical and medical androgen deprivation therapy (ADT) is a cornerstone for prostate cancer treatment, but relapse usually occurs. (sciencemag.org)
  • [13] 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)
  • [13] 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)
  • It is not yet known which regimen of radiation therapy with or without androgen-deprivation therapy is more effective for prostate cancer. (clinicaltrials.gov)
  • PURPOSE: This randomized phase III trial is studying prostate radiation therapy to see how well it works compared with short-term androgen deprivation therapy given together with pelvic lymph node radiation therapy with or without prostate radiation therapy in treating patients with a rising PSA after surgery for prostate cancer. (clinicaltrials.gov)
  • PBRT and short-term androgen deprivation [STAD]): Beginning 2 months before the start of PBRT, patients undergo STAD, using a combination of antiandrogen (AA) and LHRH agonist therapy, for a total of 4-6 months. (clinicaltrials.gov)
  • This phase II trial studies how well androgen deprivation therapy and vorinostat followed by radical prostatectomy works in treating patients with prostate cancer that has not spread to other parts of the body. (clinicaltrials.gov)
  • Giving androgen deprivation therapy and vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. (clinicaltrials.gov)
  • 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)
  • 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)
  • Cardiovascular risk patients under androgen deprivation therapy : Lower risk with GnRH antagonists compared to LHRH agonists? (urotoday.com)
  • Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists is the mainstay of treatment for metastatic prostate cancer (mCaP). (urotoday.com)
  • Long-term Castration-related Outcomes in Patients With High-risk Localized Prostate Cancer Treated With Androgen Deprivation Therapy With or Without Docetaxel and Estramustine in the UNICANCER GETUG-12 Trial. (urotoday.com)
  • Neoadjuvant chemotherapy with docetaxel and estramustine (DE) significantly improved relapse-free survival in patients with high-risk localized prostate cancer treated with androgen deprivation therapy (ADT) for 3 years and a local treatment in the GETUG-12 phase III trial. (urotoday.com)
  • Is Gleason Grade 5 Prostate Cancer Resistant to Conventional Androgen Deprivation Therapy? (harvard.edu)
  • ORLANDO -- Intermittent androgen deprivation therapy guided by cancer-related biomarkers appears to be just as effective for treatment following prostate cancer therapy as continuous hormonal treatment, researchers said here. (medpagetoday.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)
  • This therapy is known as Androgen Deprivation Therapy or ADT. (fda.gov)
  • 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. (patentgenius.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)
  • Several analogues also showed excellent in vivo activity in classic rodent models of AR antagonism, inhibiting growth of rat ventral prostate and seminal vesicles, without accompanying increases in serum gonadotropin and testosterone levels, as is seen with other AR antagonists. (nih.gov)
  • 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)
  • Antiandrogens , also known as androgen antagonists or testosterone blockers , are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. (wikipedia.org)
  • [1] [2] They can be thought of as the functional opposites of AR agonists , for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm . (wikipedia.org)
  • Androgens like testosterone and particularly DHT are importantly involved in the development and progression of prostate cancer. (wikipedia.org)
  • Androgen receptor (AR) is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. (raystarbio.cn)
  • Antagonists work by blocking the effect of testosterone, which can have a negative effect on libido and function. (globalrph.com)
  • When the testosterone and androgen levels are too. (tylerweitzman.tk)
  • Clascoterone is an antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone. (wikipedia.org)
  • LH acts on the Leydig cells to stimulate de novo sythesis of androgens (mainly testosterone). (flashcardmachine.com)
  • Limited efficacy when androgen receptor antagonists are used alone because of a compensatory increase in LH secretion stimulates higher serum concentrations of testosterone. (flashcardmachine.com)
  • The CYP17A enzyme family is involved in the biosynthesis of androgens in the testes and adrenals, culminating in the weak androgens dehydroepiandrosterone (DHEA) and androstenedione, that further undergo metabolism in peripheral tissues (and in prostate cancer cells) to form potent androgens, such as testosterone and its active metabolite dihydotestosterone (DHT). (news-medical.net)
  • One promising drug in this family is abiraterone acetate, which shows good activity against androgens and especially lowers testosterone levels, however, disease progression has not been affected. (news-medical.net)
  • Since the most potent androgen, DHT, is synthesized from testosterone in peripheral tissues by 5α reductase, any therapy that inhibits this enzyme would be potentially useful as an antiandrogen. (news-medical.net)
  • They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). (wikipedia.org)
  • An androgen that is produced from testosterone in the body and is important in the formation of the male reproductive organs and in the development of male secondary sex characteristics. (thefreedictionary.com)
  • The hemizygous mutations in the AR (Xq11.2-q12) encoding AR are associated with X-linked androgen insensitivity, and bi-allelic mutations in SRD5A2 cause enzyme deficiency, converting testosterone (T) to dihydrotestosterone (DHT). (thefreedictionary.com)
  • Natural hormone testosterone (T) and dihydrotestosterone (DHT), known as androgens, are the endogenous ligands of AR. (thefreedictionary.com)
  • Taking only an anti-androgen incurs risk of serious bone density loss, and taking only estrogen does not significantly lower testosterone levels. (trans-health.com)
  • Low-level exposure to endocrine-disrupting compounds can induce functional, developmental, behavioral, and transgenerational disturbances, as shown after low-level exposure to the fungicide vin-clozolin, which acts as an androgen antagonist in rats and mice (Anway et al. (thefreedictionary.com)
  • Interaction of organophosphate pesticides and related compounds with the androgen receptor. (thefreedictionary.com)
  • Compounds which inhibit or antagonize the biosynthesis or actions of androgens. (harvard.edu)
  • Molecules based on this series of compounds have the potential to provide unique and effective clinical opportunities for treatment of prostate cancer and other androgen-dependent diseases. (nih.gov)
  • Non-steroidal compounds which are high affinity, high specificity ligand antagonists for the androgen receptor are disclosed. (patentgenius.com)
  • Thus, this study provides a molecular insight for AA as a natural anti-androgenic compound and may serve as a basis for AA derivatives as a new chemical lead structure for novel therapeutic compounds as AR antagonists, that can be used for prophylaxis or treatment of prostatic diseases . (curehunter.com)
  • Some compounds showed very potent androgen-antagonistic activity. (elsevier.com)
  • While other compounds also suppress androgen synthesis, such as glucocorticoids, aminoglutethimide and ketoconazole, these are not considered antiandrogens as their mechanism of action does not involve the AR, but rather various routes of synthesis. (news-medical.net)
  • The second generation androgen receptor antagonists (enzalutamide and apalutamide) have the highest affinity to the androgen receptor. (altmeyers.org)
  • Modeling Acquired Resistance to the Second-Generation Androgen Receptor Antagonist Enzalutamide in the TRAMP Model of Prostate Cancer. (bvsalud.org)
  • Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration -resistant prostate cancer (CRPC) in chemotherapy -naïve as well as in patients previously exposed to chemotherapy . (bvsalud.org)
  • 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)
  • Dehydroepiandrosterone (DHEA, Prasterone, Dehydroisoandrosterone) 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)
  • Recent data report that abiraterone acetate, a specific inhibitor of CYP17 that is key to androgen and estrogen synthesis, improves survival in metastatic castration-resistant prostate cancer (CRPC), confirming the continued dependency of CRPC on the androgen receptor (AR) signaling pathway. (aacrjournals.org)
  • EDCs can exert endocrine disrupting activity on more than just estrogen, androgen, and thyroid hormone action. (wellnessresources.com)
  • Metabolite of the chemotherapeutic drug tamoxifen, exhibiting more potent estrogen agonist/antagonist activity than the parent drug. (sigmaaldrich.com)
  • BPA has estrogen and anti-androgen effects, thereby destroying the development and function of Leydig cells and causing related reproductive diseases such as testicular dysgenesis syndrome, delayed puberty, and subfertility/infertility. (frontiersin.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)
  • 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)
  • 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)
  • One mechanism that may contribute to AR reactivation is increased accumulation or synthesis of androgens by prostate cancer cells, and a subset of patients who relapse after castration or luteinizing hormone-releasing hormone agonist treatment will respond to secondary hormonal therapies with AR antagonists such as bicalutamide or to treatments that suppress residual adrenal androgen production such as ketoconozole. (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)
  • Molecular mechanism of R-bicalutamide switching from androgen receptor antagonist to agonist induced by amino acid mutations using molecular dynamics simulations and free energy calculation. (medchemexpress.com)
  • Antihormone therapy, such as flutamide, bicalutamide, and luteinizing hormone-releasing hormone agonist, may lessen the amount of androgens made by the body. (clinicaltrials.gov)
  • 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)
  • [5] These include AR antagonists , androgen synthesis inhibitors , and antigonadotropins . (wikipedia.org)
  • [5] AR antagonists work by directly blocking the effects of androgens, while androgen synthesis inhibitors and antigonadotropins work by lowering androgen levels. (wikipedia.org)
  • Nonsteroidal androgen synthesis inhibitors like ketoconazole can also be described as "NSAAs", although the term is usually reserved to describe AR antagonists. (wikipedia.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)
  • Cardiovascular Risk Profile in Prostate Cancer Patients Treated with GnRH Agonists versus Antagonists: An Italian Real-World Analysis. (urotoday.com)
  • To evaluate and compare the incidence of cardiovascular (CV) events in a large contemporary cohort of patients diagnosed with prostate cancer (PCa) and in treatment with GnRH agonists or GnRH antagonists. (urotoday.com)
  • 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)
  • 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)
  • [4] 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)
  • The representatives of the family of non-steroidal antiandrogens are potent antagonists at the androgen receptor. (altmeyers.org)
  • Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both men and women. (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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Hormone therapy is best used in combination with other treatments such as radiotherapy, chemotherapy, and androgen receptor-targeted agents. (globalrph.com)
  • By selectively occupying the strongest binding sites, AR signaling remains active even when androgen levels are low, as is characteristic of first-line androgen ablation therapy. (biomedcentral.com)
  • While androgen ablation therapy is a standard first-line treatment, the vast majority of prostate tumors eventually become hormone refractory and continue to proliferate even with very low levels of androgen. (biomedcentral.com)
  • 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)
  • GH-RH antagonists could be considered for further development for the therapy of prostate cancer, especially after the relapse. (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)
  • Not as effective for MTF hormone therapy, because it can potentially stimulate androgen production. (trans-health.com)
  • However, the AR and AR-regulated genes are still expressed at high levels in androgen-independent prostate cancer, indicating that AR transcriptional activity is reactivated in these tumors and that AR remains as a potential therapeutic target ( 1 - 4 ). (aacrjournals.org)
  • UT-34 is a selective androgen receptor degrader (SARD) ligand.Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. (raystarbio.cn)
  • The postchemotherapy study of abiraterone acetate was recently reported and confirmed that targeting of the androgen receptor (AR) is a valid therapeutic strategy in CRPC, imparting overall survival (OS) benefit in advanced prostate cancer. (aacrjournals.org)
  • What are some therapeutic uses of androgens? (flashcardmachine.com)
  • Therapeutic used of anti-androgens? (flashcardmachine.com)
  • Therapeutic uses for androgen receptor antagonists? (flashcardmachine.com)
  • The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. (bcgsc.ca)
  • This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer. (bcgsc.ca)
  • The non-steroidal androgen receptor antagonists have common structural elements with the exception of darolutamide. (altmeyers.org)
  • All test systems showed that bicalutamide and hydroxyflutamide act as potent androgen antagonists (Ma et al. (thefreedictionary.com)
  • 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)
  • 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)
  • R)-Bicalutamide is an androgen receptor (AR) antagonist, with antineoplastic activity. (medchemexpress.com)
  • 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)
  • 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)
  • Currently approved drugs aimed at androgen signaling axis include the AR antagonist bicalutamide and the CYP17 inhibitor abiraterone[ 7 ]. (biomedcentral.com)
  • [13] [15] 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)
  • Androgen receptor antagonists lead to an increase in the release of gonadotropin and must therefore be used together with GnrH analogues. (altmeyers.org)
  • What are the two GnRH antagonists to know? (flashcardmachine.com)
  • MOA of the GnRH antagonists? (flashcardmachine.com)
  • Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as nonsteroidal androgen receptor antagonists. (sigmaaldrich.com)
  • Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists derived from 1,2-dihydrop. (nih.gov)
  • 1993). The endocrine and reproductive effects of xenobiotics are believed to be due to their 1) mimicking the effects of endogenous hormones such as estrogens and androgens, 2) antagonizing the effects of normal, endogenous hormones, 3) altering the pattern of synthesis and metabolism of natural hormones, and 4) modifying the hormone receptor levels. (springer.com)
  • We report here the design and synthesis of novel androgen antagonists bearing carborane. (semanticscholar.org)
  • Design and synthesis of nonsteroidal progesterone receptor antagonists based on C,C'-diphenylcarborane scaffold as a hydrophobic pharmacophore. (semanticscholar.org)
  • Design and synthesis of androgen receptor full antagonists bearing a p-carborane cage: promising ligands for anti-androgen withdrawal syndrome. (semanticscholar.org)
  • These hormones also play an important role in facilitating protein synthesis in androgen-sensitive tissues such as skeletal muscle, bone, and the kidneys. (springer.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)
  • Flutamide (molecular formula: C11H11F3N2O3) is an oral, non-steroidal anti-androgen agent (androgen recepto. (altmeyers.org)
  • This is a prospective, single-center, two-phase study to assess the efficacy of single pulsed-dose flutamide in creating double strand breaks (DSBs) in prostate cancer within patients receiving central androgen suppression and brachytherapy. (clinicaltrials.gov)
  • To confirm DNA double strand breaks occur in prostate cancer tissue following pulse-dose flutamide administration in patients who are androgen suppressed, as compared to control patients receiving placebo. (clinicaltrials.gov)
  • 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)
  • 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 inhibited 5α-dihydrotestosterone stimulated AR reporter gene activity with an IC(50)=4.7 μM and produced a concentration dependent reduction in androgen receptor levels in prostate cancer cells. (rcsb.org)
  • Collectively, our results suggested a selective mechanism of action of degarelix against androgen steroidogenesis and AR-variants. (aacrjournals.org)
  • Cortexolone 17 alpha-propionate (CB-03-01, Clascoterone) is a topical and peripherally selective androgen antagonist, displays a strong local antiandrogenic activity in hamster's flank organ test, does not exhibit antiandrogenic activity after subcutaneous injection in vivo. (raystarbio.cn)
  • The selective androgen receptor. (tylerweitzman.tk)
  • Compound 2 retained nanomolar potency and selective inhibition of AKR1C3 but also acted as an AR antagonist. (rcsb.org)
  • It acts as a selective antagonist of the androgen receptor. (news-medical.net)
  • Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. (aacrjournals.org)
  • Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. (aacrjournals.org)
  • 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)
  • Likewise, it is significantly more efficacious as an antiandrogen than other AR antagonists such as enzalutamide and spironolactone in scalp dermal papilla cells and sebocytes in vitro. (wikipedia.org)
  • 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)
  • Coupled cistrome and transcriptome profiling upon small molecule antagonism led to the identification of a core set of AR direct effector genes that are most likely to mediate the activities of targeted agents: unbiased pathway mapping revealed that AR is a key modulator of steroid metabolism by forming a tightly controlled feedback loop with other nuclear receptor family members and this oncogenic effect can be relieved by antagonist treatment. (biomedcentral.com)
  • A compound which inhibits or antagonises the biosynthesis or actions of androgens. (ebi.ac.uk)
  • be useful for the topical treatment of androgen-dependent skin disorders such as acne, androgenetic alopecia and hirsutism. (raystarbio.cn)
  • Clascoterone, also known as cortexolone 17α-propionate or 11-deoxycortisol 17α-propionate, as well as 17α,21-dihydroxyprogesterone 17α-propionate or 17α,21-dihydroxypregn-4-en-3,20-dione 17α-propionate, is a synthetic pregnane steroid and a derivative of progesterone and 11-deoxycortisol (cortexolone). (wikipedia.org)
  • 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)
  • Kintor Pharmaceuticals is developing and commercializing a robust pipeline of small molecule and biological drugs for androgen-receptor-related disease areas with unmet medical needs, including COVID-19, prostate, breast and liver cancer, alopecia and acne. (biospace.com)
  • Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. (bcgsc.ca)
  • 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)
  • 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)
  • 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)
  • Our results indicate that GH-RH antagonist MZ-4-71 suppresses growth of PC-3, DU-145 and Dunning AT-I androgen-independent prostate cancers, through diminution of GH release and the resulting decrease in the secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-II production. (elsevier.com)
  • Inhibition of androgen biosynthesis and/or AR antagonism should be efficacious in the treatment of CRPC. (rcsb.org)
  • 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)
  • Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. (pubmedcentralcanada.ca)
  • Oral curcumin intake could inhibit androgen receptor expression and probably PSA activity. (greenmedinfo.com)
  • We herein show that orchiectomy synergizes with immunotherapy, whereas the more widely used treatment of medical ADT involving androgen receptor (AR) antagonists suppresses immunotherapy. (sciencemag.org)
  • to androgen suppresses sexual.Guyton and Hall Textbook of Medical Physiology, 12th edition pdf and chm free download.Transcriptional profiling identifies gene expression changes induced in HCV-subgenomic. (tylerweitzman.tk)
  • Various relevant study results support the importance of the androgen receptor signaling pathway in the treatment of prostate cancer. (altmeyers.org)
  • This stage, often referred to as castration-resistant prostate cancer (CRPC), is associated with an active androgen receptor (AR)-signaling pathway. (biomedcentral.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 influence of androgen and its receptor signaling pathway on sebaceous glands and sebum secretion is one of the important factors causing acne vulgaris. (biospace.com)
  • It competitively inhibits the binding of androgen in the skin tissue to the androgen receptor and can locally control the activation of the receptor signaling pathway caused by androgen hyperactivity without changing the activity of the androgen receptor signaling pathway in the human body. (biospace.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)
  • Here, we first induced cellular senescence by treating androgen-sensitive PCa LNCaP cells with either SAL or the AR antagonist Enzalutamide (ENZ). (biomedcentral.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)
  • 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)
  • 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)
  • Here, we examined the biological effects of Frzb/sFRP3 on an androgen-independent prostate cancer cell model. (elsevier.com)
  • Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with Dunning R-3327 AT-1 prostatic adenocarcinoma. (elsevier.com)
  • Androgen Antagonists" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • Androgen antagonists prevent the growth of prostate cancer cells and induce a G1 cell cycle arrest. (mskcc.org)
  • Androgens can cause the growth of prostate cancer cells. (clinicaltrials.gov)
  • All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. (bcgsc.ca)
  • Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. (bcgsc.ca)
  • 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)
  • Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue. (pharmacycode.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Recently, AR antagonists demonstrated anti-tumor activities in preclinical AR+ breast cancer models. (aacrjournals.org)
  • Androgen Optimization Simple.A receptor antagonist is a. in skeletal muscle encoded by a. rats and which increases muscle mass. (tylerweitzman.tk)
  • 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)
  • What is used with androgen receptor antagonists to treat metastatic prostate cancers? (flashcardmachine.com)