Androgen Antagonists: Compounds which inhibit or antagonize the biosynthesis or actions of androgens.Androgens: Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species.Receptors, Androgen: Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.Tosyl CompoundsCyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.Dihydrotestosterone: A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.AnilidesProstatic Neoplasms: Tumors or cancer of the PROSTATE.Androgen Receptor Antagonists: Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Testosterone Congeners: Steroidal compounds related to TESTOSTERONE, the major mammalian male sex hormone. Testosterone congeners include important testosterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with androgenic activities.Metribolone: A synthetic non-aromatizable androgen and anabolic steroid. It binds strongly to the androgen receptor and has therefore also been used as an affinity label for this receptor in the prostate and in prostatic tumors.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Androgen-Insensitivity Syndrome: A disorder of sexual development transmitted as an X-linked recessive trait. These patients have a karyotype of 46,XY with end-organ resistance to androgen due to mutations in the androgen receptor (RECEPTORS, ANDROGEN) gene. Severity of the defect in receptor quantity or quality correlates with their phenotypes. In these genetic males, the phenotypic spectrum ranges from those with normal female external genitalia, through those with genital ambiguity as in Reifenstein Syndrome, to that of a normal male with INFERTILITY.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Piperidines: A family of hexahydropyridines.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Androstenedione: A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Neoplasms, Hormone-Dependent: Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Nandrolone: C18 steroid with androgenic and anabolic properties. It is generally prepared from alkyl ethers of ESTRADIOL to resemble TESTOSTERONE but less one carbon at the 19 position.Androstane-3,17-diol: The unspecified form of the steroid, normally a major metabolite of TESTOSTERONE with androgenic activity. It has been implicated as a regulator of gonadotropin secretion.Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.3-Oxo-5-alpha-Steroid 4-Dehydrogenase: An enzyme that catalyzes the reduction of TESTOSTERONE to 5-ALPHA DIHYDROTESTOSTERONE.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Cell Line, Tumor: A cell line derived from cultured tumor cells.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Dehydroepiandrosterone Sulfate: The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE.Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Estrogens: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Cholestenone 5 alpha-Reductase: An oxidoreductase that catalyzes the conversion of 3-oxo-delta4 steroids into their corresponding 5alpha form. It plays an important role in the conversion of TESTOSTERONE into DIHYDROTESTOSTERONE and PROGESTERONE into DIHYDROPROGESTERONE.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.

The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture. (1/1203)

We have examined five human breast cancer cell lines in continuous tissue culture for androgen responsiveness. One of these cell lines shows a 2- to 4-fold stimulation of thymidine incorporation into DNA, apparent as early as 10 hr following androgen addition to cells incubated in serum-free medium. This stimulation is accompanied by an acceleration in cell replication. Antiandrogens [cyproterone acetate (6-chloro-17alpha-acetate-1,2alpha-methylene-4,6-pregnadiene-3,20-dione) and R2956 (17beta-hydroxy-2,2,17alpha-trimethoxyestra-4,9,11-triene-1-one)] inhibit both protein and DNA synthesis below control levels and block androgen-mediated stimulation. Prolonged incubation (greater than 72 hr) in antiandrogen is lethal. The MCF- cell line contains high-affinity receptors for androgenic steroids demonstrable by sucrose density gradients and competitive protein binding analysis. By cross-competition studies, androgen receptors are distinguishable from estrogen receptors also found in this cell line. Concentrations of steroid that saturate androgen receptor sites in vitro are about 1000 times lower than concentrations that maximally stimulate the cells. Changes in quantity and affinity of androgen binding to intact cells at 37 degrees as compared with usual binding techniques using cytosol preparation at 0 degrees do not explain this difference between dissociation of binding and effect. However, this difference can be explained by conversion of [3H]-5alpha-dihydrotestosterone to 5alpha-androstanediol and more polar metabolites at 37 degrees. An examination of incubation media, cytoplasmic extracts and crude nuclear pellets reveals probable conversion of [3H]testosterone to [3H]-5alpha-dihydrotestosterone. Our data provide compelling evidence that some human breast cancer, at least in vitro, may be androgen dependent.  (+info)

Pharmacokinetics of flutamide in patients with renal insufficiency. (2/1203)

AIMS: The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD) clearance of flutamide and hydroxyflutamide was also determined. METHODS: Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26 male subjects with normal renal function (creatinine clearance by 24 h urine collection, CLcr, greater than 80 ml min(-1) 1.73 m(-2); n=6) or reduced renal function; CLcr=50-80 (n=7), 30-49 (n=3), 5-29 (n=4), and <5 ml min(-1) 1.73 m(-2)-HD (n=6), following a single, oral 250 mg flutamide dose. Subjects undergoing HD received a second 250 mg dose of flutamide 4 h prior to HD; blood and dialysate were collected during HD to determine dialysability of flutamide and hydroxyflutamide. RESULTS: Cmax, tmax, AUC, t1/2, and renal clearance of flutamide and hydroxyflutamide did not differ between groups. Less than 1% of the dose appeared in dialysate as hydroxyflutamide. No serious adverse events were observed. CONCLUSIONS: Renal function did not affect flutamide nor hydroxyflutamide disposition. HD did not alter hydroxyflutamide pharmacokinetics. Dosing adjustments for renal impairment or HD are not indicated for flutamide.  (+info)

Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. (3/1203)

Transcription of the prostate-specific antigen (PSA) gene escapes regulation by androgens in advanced prostate cancer. To determine the molecular mechanism(s) of androgen-independent regulation of the PSA gene, the possibility that the androgen receptor (AR) is activated in the absence of androgen by stimulation of protein kinase A (PKA) was investigated. Activation of PKA by forskolin resulted in elevated expression of the PSA gene in androgen-depleted LNCaP cells, an effect that was blocked by the antiandrogen, bicalutamide. Further evidence that induction of PSA gene expression was dependent on AR was obtained from experiments using PC3 cells devoid of AR. Neither PSA, PB, nor ARR3 androgen-responsive reporters could be induced by activation of PKA in the absence of transfected AR. In addition, when nuclear AR from forskolin-treated LNCaP cells was incubated with oligonucleotides encoding an androgen response element of the PSA promoter and examined by electromobility shift assay, an increase in AR-androgen response element complex formation was observed. Lastly, cotransfection of an expression vector for a chimeric protein encoding the amino-terminal domain of the human AR linked to Gal4 and a 5xGal4UAS reporter gene construct resulted in activation of the amino-terminal domain of the AR by stimulation of PKA activity. These results demonstrate androgen-independent induction of PSA gene expression in prostate cancer cells by an AR-dependent pathway.  (+info)

Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency? (4/1203)

PURPOSE: The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjogren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjogren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis. METHODS: Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects. RESULTS: Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy. CONCLUSIONS: Androgen deficiency may promote the progression of Sjogren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjogren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans.  (+info)

From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. (5/1203)

Overexpression of the HER2/Neu protooncogene has been linked to the progression of breast cancer. Here we demonstrate that the growth of prostate cancer LNCaP cells can also be increased by the stable transfection of HER2/Neu. Using AG879, a HER2/Neu inhibitor, and PD98059, a MAP kinase inhibitor, as well as MAP kinase phosphatase-1 (MPK-1), in the transfection assay, we found that HER2/Neu could induce prostate-specific antigen (PSA), a marker for the progression of prostate cancer, through the MAP kinase pathway at a low androgen level. Reporter assays and mammalian two-hybrid assays further suggest this HER2/Neu-induced androgen receptor (AR) transactivation may function through the promotion of interaction between AR and AR coactivators, such as ARA70. Furthermore, we found this HER2/Neu --> MAP kinase --> AR-ARAs --> PSA pathway could not be blocked completely by hydroxyflutamide, an antiandrogen used in the treatment of prostate cancer. Together, these data provide a novel pathway from HER2/Neu to AR transactivation, and they may represent one of the reasons for the PSA re-elevation and hormone resistance during androgen ablation therapy in prostate cancer patients.  (+info)

Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations. (6/1203)

Differential gene expression between the androgen sensitive human prostate cancer cell line LNCaP and an insensitive clonal variant, LNCaP-r, was demonstrated by suppression subtractive hybridization. Twenty-one sequences were identified of which 9 are homologous to known genes, 11 are represented by expressed sequence tags (ESTs), and 1 is novel. We present data for 5 of 7 sequences confirmed to be differentially expressed by Northern blot analysis and semiquantitative RT-PCR. Only one gene, fibronectin (FN), was highly overexpressed (>60-fold) in LNCaP-r cells, consistent with previously reported overexpression of FN in prostate cancer. Four sequences were down-regulated in LNCaP-r cells, including an inactive variant of the E2 ubiquitin conjugating enzyme (UEV-1), a novel metalloproteinase-related collagenase (PM5), and a potential tumor suppressor gene (breast basic conserved gene, BBC1). UEV-1 is multifunctional, regulates the cell cycle via cdk1, has homology to MMS2 and likewise functions as a DNA protection protein, and also has homology to TSG101. Aberrant splice variants of TSG101 occur frequently in both breast and prostate cancer, but its mechanism of action is unknown. FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression.  (+info)

Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer. (7/1203)

The INK4A gene maps to the 9p21 region and was initially described [M. Serrano et al., Nature (Lond.), 366: 704-707, 1993; A. Kamb et al., Science (Washington DC), 264: 436-440, 1994] as encoding a 148-amino-acid protein termed p16. The p16 protein associates exclusively with Cdk4 and Cdk6, inhibiting their complexation with D-type cyclins and the consequent phosphorylation of pRb. This contributes to cell cycle arrest. The purpose of the present study was to evaluate patterns of p16 expression in a well-characterized cohort of prostatic adenocarcinomas while exploring potential associations between alterations of p16 and clinicopathological variables. Normal and malignant tissues from 88 patients with prostate carcinoma were examined. In situ hybridization and immunohistochemistry assays were used to determine the status of the INK4A exon 1alpha transcripts and levels of p16 protein, respectively. Associations between altered patterns of expression and clinicopathological variables, including pretreatment prostate-specific antigen (PSA) level, Gleason grade, pathological stage, and hormonal status, were evaluated using the Mantel-Haenszel chi2 test. Biochemical (PSA) relapse after surgery was evaluated using the Kaplan-Meier method and the log-rank test. Levels of p16 expression and INK4A exon 1alpha transcripts in normal prostate and benign hyperplastic tissues were undetectable. However, p16 nuclear overexpression was observed in 38 (43%) prostate carcinomas, whereas the remaining 50 (57%) cases showed undetectable p16 levels. Overexpression of p16 protein was found to correlate with increased INK4A exon 1alpha transcripts. Moreover, p16 overexpression was associated with a higher pretreatment PSA level (P = 0.018), the use of neoadjuvant androgen ablation (P = 0.001), and a sooner time to PSA relapse after radical prostatectomy (P = 0.002). These data suggest that p16 overexpression is associated with tumor recurrence and a poor clinical course in patients with prostate cancer.  (+info)

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. (8/1203)

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment.  (+info)

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.
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 ...
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.
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.
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 ...
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.
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 ...
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
Men with unfavorable-risk prostate cancer and moderate or severe comorbidities had significantly decreased overall and cardiac mortality when treated with radiotherapy alone vs radiotherapy and androgen-deprivation therapy, according to a study described in a research letter in JAMA. In the letter, DAmico et al present long-term follow-up to their randomized trial, reported in JAMA in 2008, that showed 6 months of androgen-deprivation therapy and radiotherapy vs radiotherapy alone "prolongs survival and is the standard treatment for unfavorable-risk prostate cancer.". The new findings build on a "post-randomization hypothesis-generating analysis suggesting that men with moderate or severe comorbidity had no increased survival from combined therapy," the researchers noted. "Using updated data from our randomized trial, we compared overall survival and mortality from prostate cancer, cardiac, or other causes in all men and those within comorbidity subgroups by randomized treatment group," the ...
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 ...
PHILADELPHIA (February 25, 2020) - Vladimir Kolenko, MD, PhD, received the two-year $200,000 NCI grant to target cholesterol homeostasis using genetic and pharmacological approaches in order to reinstate or re-emphasize sensitivity of prostate cancer cells to anti-androgens like abiraterone and enzalutamide.
A Phase III Randomized Trial Comparing Androgen Deprivation Therapy + TAK-700 with Androgen Deprivation Therapy + Bicalutamide in Patients with Newly Diagnosed Metastatic Hormone Sensitive Prostate ...
Background:Hormone therapy is commonly used with radiotherapy in the treatment of prostate cancer. Aim:To provide a single-institution analysis of the benefits of hormone therapy with radiotherapy in...
At a median follow-up of nearly 52 months, the treatment regimen deceased mortality risk among men with high-risk metastatic castration-naive prostate cancer by 30%.
The present analysis is to our knowledge the first one that addresses the role of PMRT as a potential cause of cardiac morbidity in prostate cancer patients receiving androgen suppression therapy. It was performed both in cancer patients and randomly selected individuals having had CT examinations for other medical reasons. The results in these groups were largely comparable. We used 3-D treatment planning with display of isodose distributions and dose-volume histograms only in those patients whose CT scans already were entered into the treatment planning system, i.e. prostate cancer patients, and only if the LAD could be identified. Data from these patients suggest that parts of the left ventricle might be exposed to 50-80% of the prescription dose, even if the mean doses in general are low. Studies in electron boost treatment for breast cancer have also shown that the heart might be exposed to unexpected radiation doses in a proportion of these patients [12]. The present data suggest that ...
The purpose of this study is to describe the safety and tolerability of up to 5 years (ie, 3 years under the 20040138 Amgen study and 2 years on this s
Given the positive-feedback circuit linking AR axis stimulation and DNA repair, it would suggest, in principle, that targeting the AR axis represents a very sound and attractive strategy for potentiating the DNA-damaging effects of cytotoxic therapies in prostate cancer. Importantly, it was observed in primary prostate cancer specimens undergoing neoadjuvant androgen deprivation therapy (ADT), that inhibition of the AR axis leads to a reduction of Ku protein expression in post-ADT prostate biopsies (5). In this first-in-human proof-of-mechanism study, Tarish and colleagues demonstrated longitudinally that castration primarily affected both Ku and DNA-PKcs expression in response to radiotherapy, leading to significant impairment of the nonhomologous end-joining (NHEJ) pathway of DSB (5). In parallel, Polkinghorn and colleagues and Goodwin and colleagues also observed a radiosensitization effect as a consequence of androgen blockade, and attributed this to the transcriptional downregulation of DNA ...
In our cohort of 80 844 patients, ADT was associated with an increased rate of fracture in both non-metastatic patients (aHR = 1.34; 95% confidence interval [CI] = 1.29-1.39) and metastatic patients (aHR = 1.51; 95%CI = 1.36-1.67). Fracture rates increased with increasing cumulative GnRH dose but decreased with increasing number of months since last use in each dose category. The mortality rate doubled for men experiencing a fracture after their diagnosis compared with that for men who did not experience a fracture (aHR = 2.05; 95%CI = 1.98-2.12). ...
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Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. Between 1989 and 1999,.... ...
J Clin Oncol. 2003 May 1;21(9):1653-9. Clinical Trial; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Govt
For men with bladder cancer, androgen suppression therapy may be prophylactic for intravesical recurrence, according to a study published in the February issue of The Journal of Urology.
Peripheral androgen blockade is feasible for prostate cancer patients who experience biochemical failure after definitive local therapy.
WASHINGTON - The cardiovascular effects of androgen deprivation therapy (ADT) for men with advanced prostate cancer are less severe than once feared, but there
Health, ...Lake Tahoe CA October 11 2007 Cancer researchers have long worked ...The presence of these proteins may explain why some prostate cancers b...Androgen-deprivation therapy is routinely used in the treatment of adv...Investigators Peter Nelson M.D. Elahe Mostaghel M.D. Ph.D. and Br...,New,research,may,show,why,some,prostate,cancer,recurs,after,treatment,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Background: There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. 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. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as
Dit weekend zit ik in Edinburgh, de hoofdstad van Schotland. Niet om alleen maar uit te rusten maar ook om verslag te doen van een stad in beweging. Een stad vol met studenten die garant staan voor een levendige stad en geen ingezakte, grijze massa ...
A regimen found useful for treating hot flashes in female cancer patients failed to relieve vasomotor symptoms in prostate cancer patients treated with androgen deprivation therapy, according to a ran
BACKGROUND: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care. METHODS: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care ...
Statin use may slow prostate cancer progression in patients receiving androgen deprivation therapy, but more trials are needed to confirm benefits, researchers say
Background: Although androgen deprivation therapy initially decreases PC tumor burden, resistance to further androgen receptor (AR)-directed treatments or chemotherapy is inevitable once CRPC is established. We postulated that the stress of ADT triggers widespread alterations in expression that renders a metastable physiologic state conditioned by epigenetic changes that might be initially reversible by targeting non-androgen pathways. We conducted a pilot study to explore genome-wide expression alterations in PC foci surviving 3 months ADT (eADT).. Methods: mRNA from 7 frozen microdissected PC foci and normal counterparts (NC) were processed for RNA-seq. RNA-seq changes in eADT specimens were compared first with NC and the untreated PC in the TCGA PRAD (TCGA) database to castrate resistant (mCRPC) specimens in the dbGAP study phs000915.v1.p1database. The raw data (fastq files) was quantified using kallisto, normalized by TMM using R package edgeR, batch effects corrected using R package SVA. ...
Prostate cancer hormone therapy, also called androgen deprivation therapy (ADT), is used to suppress the amount of testosterone produced by the body.
Antiandrogens Definition - Anti-androgens are a diverse group of medicines that counteract the effects of excess amounts of androgens or male sex...
Az ablakba alul másold be az egész mondatot, ahol a kifejezést találtad, hogy másoknak könnyebb legyen megoldani a kifejezés jelentését ...
... s, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like ... N-Terminal domain antagonists[edit]. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all ... Androgen antagonists; Androgen blockers; Testosterone blockers. Use. • Men and boys: Prostate cancer; Benign prostatic ... Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3 ...
Tindall, D.J.; Chang, C.H.; Lobl, T.J.; Cunningham, G.R. (1984). "Androgen antagonists in androgen target tissues". ... Lerner, Leonard J. (1975). "Androgen antagonists". Pharmacology & Therapeutics. Part B: General and Systematic Pharmacology. 1 ... It was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and ...
"Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3): 367-400. PMID 6205409. Singh SM, Gauthier S, Labrie ... It is a selective antagonist of the androgen receptor and consequently has progonadotropic effects by increasing gonadotropin ... "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211-47. PMID 10637363 ... Thomson, D. S. (1989). "Pharmacology of Anti-androgens in the Skin". 87 / 2: 483-493. doi:10.1007/978-3-642-74054-1_36. ISSN ...
Ran F, Xing H, Liu Y, Zhang D, Li P, Zhao G (2015). "Recent Developments in Androgen Receptor Antagonists". Arch. Pharm. ( ... RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) which was first described in 1994 and was ... RU-59063 has high affinity for the human androgen receptor (AR) (Ki = 2.2 nM; Ka = 5.4 nM) and 1,000-fold selectivity for the ... Liu B, Su L, Geng J, Liu J, Zhao G (2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ...
They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211-47. doi:10.2174/ ... An over-the-counter histamine H2 receptor antagonist that also shows very weak activity as an AR antagonist. Also inhibits ...
Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP (July 2002). "Bicalutamide functions as an androgen receptor antagonist by ... Bicalutamide acts as a highly selective competitive silent antagonist of the androgen receptor (AR) (IC50 = 159-243 nM), the ... Antigonadotropic agents like high-dose CPA, high-dose androgens (e.g., testosterone esters), and GnRH antagonists (though ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ...
They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like ... Specifically acts as an AR antagonist, weak antigonadotropin, and weak steroidogenesis inhibitor. Used for androgen-dependent ... 99-. ISBN 978-1-60327-829-4. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ... Due to their antigonadotropic effects, SAAs lower androgen levels in addition to directly blocking the actions of androgens at ...
... acts as a selective antagonist of the androgen receptor (AR), competing with androgens like testosterone and ... Helsen C, Van den Broeck T, Voet A, Prekovic S, Van Poppel H, Joniau S, Claessens F (Aug 2014). "Androgen receptor antagonists ... Sundblad C, Landén M, Eriksson T, Bergman L, Eriksson E (2005). "Effects of the androgen antagonist flutamide and the serotonin ... In contrast to GnRH agonists, GnRH antagonists don't cause an initial androgen surge, and are gradually replacing GnRH agonists ...
321-. ISBN 978-1-901865-55-4. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ...
Similarly to flutamide, AA560 is a selective antagonist of the androgen receptor (AR) and consequently shows progonadotropic ... Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ...
Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... ISBN 978-1-4831-4566-2. R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 [44], is a powerful ... Brueggemeier, Robert W. (2006). "Sex Hormones (Male): Analogs and Antagonists". doi:10.1002/3527600906.mcb.200500066. ... derivative which was never marketed for medical use but has been widely used in scientific research as a hot ligand in androgen ...
In fact, it is actually an antagonist of the androgen receptor (AR) and hence has antiandrogenic activity, said to be about 30 ... 63-. ISBN 978-3-319-20185-6. Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure- ... It shows antagonist activity by binding to the AR, and hence produces an antiandrogenic action equivalent to ca. 40% of the ... Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen ...
... acts as a selective antagonist of the androgen receptor (AR), preventing the effects of androgens like testosterone ... Nilutamide acts as a selective competitive silent antagonist of the AR (IC50 = 412 nM), which prevents androgens like ... 11-. ISBN 978-981-256-920-2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... De Voogt, H. J.; Rao, B. R.; Geldof, A. A.; Gooren, L. J. G.; Bouman, F. G. (1987). "Androgen action blockade does not result ...
Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... ISBN 978-1-60327-829-4. Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): ... "Androgen receptor antagonists for prostate cancer therapy". Endocrine-Related Cancer. 21 (4): T105-18. doi:10.1530/ERC-13-0545 ... "Drug safety is a barrier to the discovery and development of new androgen receptor antagonists". The Prostate. 71 (5): 480-8. ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Differential effects on high-androgen responder and low-androgen responder muscle groups". Endocrinology. 154 (12): 4594-606. ... It is reported to possess an IC50 of 700 nM for the androgen receptor (AR), about 4-fold less than that of bicalutamide. ...
CPA is a potent androgen receptor (AR) competitive antagonist. It directly blocks endogenous androgens such as testosterone and ... CPA is known to possess the following pharmacological activity: Androgen receptor (AR) antagonist/very weak partial agonist ( ... ISBN 978-1-84076-013-2. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... In addition, although CPA reduces androgen production in the gonads, it can increase the production of adrenal androgens, in ...
ISBN 978-3-527-30247-5. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ...
Gauthier S, Martel C, Labrie F (October 2012). "Steroid derivatives as pure antagonists of the androgen receptor". The Journal ... Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity ... In the cortex and pituitary, androgens do not undergo significant aromatization, and it appears that the effects of androgens ... Balk SP (September 2002). "Androgen receptor as a target in androgen-independent prostate cancer". Urology. 60 (3 Suppl 1): 132 ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Seborrhea is recognized as an androgen-sensitive condition - that is, it is caused or aggravated by androgen sex hormones such ... "Androgen Physiology, Pharmacology and Abuse". PMID 25905231. Kenneth L. Becker (2001). Principles and Practice of Endocrinology ... Zouboulis, Christos C.; Degitz, Klaus (2004). "Androgen action on human skin - from basic research to clinical significance". ...
Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr ... List of androgens/anabolic steroids R.A. Hill; H.L.J. Makin; D.N. Kirk; G.M. Murphy (23 May 1991). Dictionary of Steroids. CRC ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Rosterolone is a derivative of mesterolone, which, in contrast, is an androgen and anabolic steroid. Steroidal antiandrogen ...
... acts as a selective silent antagonist of the androgen receptor (AR), the biological target of androgens like ... Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... "Drug safety is a barrier to the discovery and development of new androgen receptor antagonists". The Prostate. 71 (5): 480-8. ... "Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC ...
... is a selective competitive antagonist of the androgen receptor (AR), although it is described as an "only relatively weak ... ISBN 978-1-4831-6510-3. Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists ( ... is not an androgen antagonist within the central nervous system". Steroids. 34 (2): 139-149. doi:10.1016/0039-128X(79)90043-6. ... On the basis of animal research, BOMT does not appear to act as an AR antagonist in central nervous system tissues, and in ...
Rathkopf D, Scher HI (2013). "Androgen receptor antagonists in castration-resistant prostate cancer". Cancer Journal. 19 (1): ... Kawahara, Takashi; Miyamoto, Hiroshi (2014). "Androgen Receptor Antagonists in the Treatment of Prostate Cancer". Clinical ... acting as a selective competitive antagonist of the androgen receptor (AR), but shows some advantages, including greater ... a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer ...
Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity ... Seborrhoea is recognized as an androgen-sensitive condition - that is, it is caused or aggravated by androgen sex hormones such ... In accordance with the involvement of androgens in seborrhoea, antiandrogens, such as cyproterone acetate,[30] spironolactone,[ ... Zouboulis, Christos C.; Degitz, Klaus (2004). "Androgen action on human skin - from basic research to clinical significance". ...
Androgen receptor modulators. Progesterone receptor modulators. List of estrogens. This article about a steroid is a stub. You ... Antagonists. *(R,R)-THC. *7β-Hydroxy-DHEA. *Chloroindazole. *Cytestrol acetate. *EM-800 (SCH-57050) ...
Pharmacological Actions : Androgen Antagonists, Antiproliferative , Wnt/β-catenin signaling pathway modulation. Additional ... 6 Abstracts with Androgen Antagonists Research. Filter by Study Type. Animal Study. ... A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic mice. Oct 15, 2008. ... A compound within Pygeum bark antagonizes human androgen receptor in the prostate gland. Sep 23, 2009. ...
Androgen antagonist synonyms, Androgen antagonist pronunciation, Androgen antagonist translation, English dictionary definition ... of Androgen antagonist. n. A substance that inhibits the biological effects of androgenic hormones ... 18) Low androgen levels, such as in those who are androgen deficient or using androgen antagonists, can result in reduced ... Androgen antagonist - definition of Androgen antagonist by The Free Dictionary https://www.thefreedictionary.com/Androgen+ ...
Androgen Antagonists Overview. Androgen Antagonists Disease Associated. Androgen Antagonists Pipeline Therapeutics. Androgen ... Androgen Antagonists Assessment by Molecule Type. Androgen Antagonists Assessment by Stage and Molecule Type. Androgen ... Androgen Antagonists Assessment by Combination Products. Androgen Antagonists Assessment by Route of Administration. Androgen ... Androgen Antagonists Assessment by Combination Products. Androgen Antagonists Assessment by Route of Administration. Androgen ...
An androgen receptor N-terminal domain antagonist for treating prostate cancer. Jae-Kyung Myung,1 Carmen A. Banuelos,1 Javier ... Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J Biol Chem. ... The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced ... Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009;138(2):245-256 ...
"Androgen Antagonists" by people in Harvard Catalyst Profiles by year, and whether "Androgen Antagonists" was a major or minor ... "Androgen Antagonists" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Androgen Antagonists" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Androgen Antagonists". ...
Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as nonsteroidal androgen receptor antagonists.. [ ...
Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists ... Analogues inhibit AR-mediated reporter gene expression and bind to AR as potently as or better than any known AR antagonists. ... Androgen receptor / NR3C4 - data and references - Guide to Pharmacology. Miscellaneous. *TESTOSTERONE - Hazardous Substances ... A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human androgen ...
A series of nonsteroidal human androgen receptor (hAR) antagonists based on 8-substituted 1,2-dihydro- and 1,2,3,4-tetrahydro-2 ... Effects of isosteric pyridone replacements in androgen receptor antagonists based on 1,2-dihydro- and 1,2,3,4-tetrahydro-2,2- ... Androgen Antagonists/chemical synthesis*. *Androgen Antagonists/pharmacology. *Androgen Receptor Antagonists*. *Androgens/ ...
Galeterone is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, ... Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. ... Bicalutamide is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. ... Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. ...
... is androgen-receptor inhibitor. Highly recommended inhibitor in AR research. Find all the information about MDV3100 ( ... Galeterone is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, ... Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. ... Bicalutamide is an androgen receptor (AR) antagonist with IC50 of 0.16 μM in LNCaP/AR(cs)cell line. ...
... antagonists for the androgen receptor are disclosed. Also disclosed are methods for employing the disclosed compounds for ... modulating processes mediated by the androgen receptor and for treating patients requiring androgen receptor antagonist therapy ... androgen receptor antagonist therapy.. Claim:. We claim:. 1. A method of antagonizing androgen activity comprising the in vivo ... steroid androgen receptor antagonist compounds disclosed can be readily utilized in pharmacological applications where androgen ...
1998) Assays to Measure Estrogen and Androgen Agonists and Antagonists. In: del Mazo J. (eds) Reproductive Toxicology. Advances ... Olea, N., Sakabe, K., Soto, A.M. and Sonnenschein, C., 1990, The proliferative effect of "anti-androgens" on the androgen- ... DDE is a potent androgen receptor antagonist, Nature. 375: 581.PubMedCrossRefGoogle Scholar ... Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor, ...
... but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in ... Persistent DDT metabolite p,p-DDE is a potent androgen receptor antagonist Nature. 1995 Jun 15;375(6532):581-5. doi: 10.1038/ ... they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT ... DDE and related environmental chemicals may be mediated at the level of the androgen receptor. ...
Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer.. Youzhi Tong, Chunyun ... Androgen Receptor (AR) antagonists have been used in clinic to treat prostate cancer. One example is bicalutamide (Casodex®), ... Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. [abstract]. In: Proceedings of the ... Abstract 2460: Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer. ...
Bradykinin Receptor Antagonists. Class Summary. Bradykinin receptor antagonists such as icatibant inhibit bradykinin from ... Androgens. Class Summary. Oral androgens have provided the most successful preventive therapy. Synthetic attenuated androgens ( ... Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline]. ... Hepatotoxicity (more commonly observed in the group receiving 17 alpha alkylated androgen) has not been observed. Oxandrolone ...
GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ... GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 ...
Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res 1999; 59: 2511-5. ... The mechanisms by which androgen receptor (AR) antagonists inhibit AR activity, and how their antagonist activity may be ... antagonist. Introduction. The androgen receptor (AR) plays a central role in prostate cancer development and progression, and ... Activity of Androgen Receptor Antagonist Bicalutamide in Prostate Cancer Cells Is Independent of NCoR and SMRT Corepressors. ...
... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ... represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer ...
We report here the design and synthesis of novel androgen antagonists bearing carborane. The most potent compounds, the ... Further development of the potent carborane-containing androgen antagonists described here, having a new skeletal structure and ... as well as in cell growth inhibition assay using androgen-dependent SC-3 cells. ... unique characteristics, may yield novel therapeutic agents, especially selective androgen receptor modulators. ...
The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate ... The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate ... Inhibition of human AR by androgen ablation therapy and by applying synthetic anti-androgens is therefore the primary goal in ... Importantly, AA is able to efficiently repress the growth of both the androgen-dependent LNCaP and also the androgen- ...
The effects of natural ligands of hormone receptors and their antagonists on telomerase activity in the androgen sensitive ... The effects of natural ligands of hormone receptors and their antagonists on telomerase activity in the androgen sensitive ... antagonists tamoxifen and bicalutamide on telomerase activity and expression of cell cycle related proteins in the androgen- ... antagonists tamoxifen and bicalutamide on telomerase activity and expression of cell cycle related proteins in the androgen- ...
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like ... N-Terminal domain antagonists[edit]. N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all ... Androgen antagonists; Androgen blockers; Testosterone blockers. Use. • Men and boys: Prostate cancer; Benign prostatic ... Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues". Pharmacol. Ther. 24 (3 ...
Androgen Antagonists. Androgen antagonists prevent the growth of prostate cancer cells and induce a G1 cell cycle arrest. The ... We are studying the effect of these antagonists on p27, cyclin E, and cyclin D/cdk complexes. We are also interested in ...
Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or ... Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen ... glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin which ...
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. Androgen ... and then stimulates transcription of androgen responsive genes. The androgen receptor is most closely related to the ... Mutations in this gene are also associated with complete androgen insensitivity (CAIS) ... Androgen receptor (AR) is a type of nuclear receptor that is activated by binding of either of the androgenic hormones ...
  • 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)
  • 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)
  • The normal development and function of the male reproductive system is dependent on the action of endogenous androgens (review and references therein, [ 10 ]) and the biological functions of androgens are primarily mediated by the AR [ 13 , 14 ], which is expressed in many organs including the hypothalamus, pituitary, liver, prostate, and testes. (pubmedcentralcanada.ca)
  • Surprisingly, ABT263 lacks senolytic effect in both AR agonist- and antagonist-pretreated cells. (biomedcentral.com)
  • These data indicate a difference in the agonist- or antagonist-induced cellular senescence and suggest a novel role of MK2206 as a senolytic agent preferentially for AR antagonist-treated cells. (biomedcentral.com)
  • Taken together, our data suggest that both AR agonist and antagonist induce cellular senescence but differentially upregulate a pro-survival signaling which preferentially sensitize androgen-sensitive PCa LNCaP cells to a specific senolytic compound. (biomedcentral.com)
  • Importantly, AA is able to efficiently repress the growth of both the androgen-dependent LNCaP and also the androgen-independent C4-2 Pca cells but not that of PC3 or CV1 cells lacking AR. (curehunter.com)
  • Treatment of human prostate carcinoma‐derived LNCaP cells with androgen or oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor β with Src, activates the Src/Raf‐1/Erk‐2 pathway and stimulates cell proliferation. (embopress.org)
  • Androgen Antagonists" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)