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Randomized phase II study to investigate the efficacy, safety and tolerability of ZK 230211 (100 mg vs. 25 mg) as second-line endocrine therapy for postmenopausal women with hormone receptor-positive metastatic breast cancer.Once the cancer has spread beyond the lymph nodes to areas such as e.g. the skin, soft tissues, lung, and liver it is called metastatic breast cancer. Patients who have been diagnosed with metastatic breast cancer that has progressed since their previous cancer treatment and that cannot be removed completely by surgery are eligible to be treated within this trial.Treatment with a new drug called Progesterone Receptor Antagonist ZK 230211 (ZK PRA) targets the progesterone receptor which may be expressed on breast cancer tumour cells. Therefore only patients with this progesterone receptor on their tumour cells can be included in this study.Progesterone receptor antagonists (including onapristone) have already shown efficacy in postmenopausal women with advanced breast cancer ...

Several AMPA antagonists have been developed as neuroprotective compounds and have entered clinical development. None of these compounds has reached phase 3 clinical trials, and unacceptable adverse events can be the main obstacle. The most prominent finding of this study was that the administration of the AMPA antagonist ZK200775 in ischemic stroke patients resulted in a transient neurological deterioration, which was associated with a higher than expected rise in serum S-100B levels. The level of sedation was more severe in stroke patients and occurred later than in normal subjects during the phase 1 studies. Besides a longer infusion time and higher doses in stroke patients, blood-brain barrier disruption, with increased tissue concentrations, may be responsible for these differences. Although baseline stroke characteristics were not equally distributed in all treatment groups, this is not a sufficient explanation for the difference in serum S-100B levels between the placebo group and dose ...

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This is a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Stage 1: Six dose cohorts, 5 using the extended release tablet (ER) formulation (10 mg BID, 20 mg BID, 30 mg BID, 40 mg BID, 50 mg BID) and 1 using the immediate-release (IR) tablet formulation 100 mg QD will be randomized in parallel. After enrollment of 36 patients in Stage 1, a dose of 50 mg BID was determined to be the RP2D. Stage 2: An additional 10 patients with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma (Stage 2a) will be enrolled at the RP2D. Based on the response in Stage 2a, the cohort will be further expanded by up to 19 more patients to a total of 29 patients to confirm the efficacy and safety profile of onapristone in this selected patient population (Stage 2b ...

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Looking for online definition of antiprogestin in the Medical Dictionary? antiprogestin explanation free. What is antiprogestin? Meaning of antiprogestin medical term. What does antiprogestin mean?

Progestin antagonists inhibit the proliferation of progesterone receptor-positive cells, including breast cancer cells, by G1 phase-specific actions, but the molecular targets involved are not defined. Reduced phosphorylation of pRB, a substrate for G1 cyclin-dependent kinases (CDKs) in vivo, was apparent after 9 h treatment of T-47D breast cancer cells with the antiprogestins RU 486 or ORG 31710, accompanying changes in S phase fraction. Although the abundance of cyclin D1, Cdk4, and Cdk6 did not decrease cyclin D1-associated kinase activity was reduced by approximately 50% at 9-18 h. Similarly, cyclin E-associated kinase activity decreased by approximately 60% at 12-24 h in the absence of significant changes in the abundance of cyclin E and Cdk2. The CDK inhibitor p21 increased in mRNA and protein abundance and was present at increased levels in cyclin D1 and cyclin E complexes at times when their kinase activity was decreased. Increased p21 protein abundance was observed in another antiprogestin

TY - JOUR. T1 - Progestins and antiprogestins in mammary tumour growth and metastasis. AU - Shi, Y. Eric. AU - Liu, Yiliang E.. AU - Lippman, Marc E.. AU - Dickson, Robert B.. N1 - Copyright: Copyright 2016 Elsevier B.V., All rights reserved.. PY - 1994/6. Y1 - 1994/6. N2 - Growth of the normal mammary gland involves proliferation, differentiation, programmed cell death and remodelling of the basement membrane throughout the cyclic ovarian stimulation of the menstrual cycle and the pregnancy/lactation cycle. The regulation of these processes involves a balance between the actions of oestrogen and progesterone. Although it is generally accepted that oestrogens are the major adverse hormonal factor in onset and progression of human breast cancer, recent studies suggest that progesterone and its synthetic progestins may be more important than oestrogen as an ovarian stimulus in driving proliferation of normal human and rodent mammary epithelium. One might expect that some aspects of these complex ...

www.MOLUNA.de The Antiprogestin Steroid RU 486 and Human Fertility Control [4202858] - Ru 486: An Antiprogestin Steroid With Contragestive Activity In Women.- Analogues Of Ru 486 For The Mapping Of The Progestin Receptor: Synthetic And Structural Aspects.- Pharmacological Profile Of Ru 486 In Animals.- The Use Of The Antiprogesterone Compound Ru 486 To Control Timing Of Parturition In Rats.- In Vivo Assessment

The effect of RU486, a synthetic progesterone receptor antagonist, on basal uterine prostaglandin (PG) release and release in response to oxytocin injection has been investigated in late-pregnant sheep (days 135-140 of gestation). Fifteen hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4), bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals. Uteroovarian vein concentrations of 13,14-dihydro-15-keto PGF2α (PGFM) and PGE2 were determined before and during oxytocin stimulation. Basal concentrations of both PGFM and PGE2 were significantly (P , 0·001) increased in ewes 15 h after RU486 administration compared with ewes receiving vehicle alone. Concentrations of PGFM, but not PGE2, increased significantly (P , 0·001) following injection of each dose of oxytocin in both treated and untreated animals. The response to oxytocin, measured both as the area under the curve and as ...

RU-486 is an abortifacient which is used to terminate early pregnancy. It acts by blocking progesterone receptor. In our earlier study with progesterone, RU-486 was used as a progesterone receptor antagonist to find out the mechanism of progesterone action on melanoma cells. Results indicated that the effect of progesterone was not mediated through progesterone receptor. In the course of experiments, it was observed that RU-486 by itself inhibited mouse melanoma cell growth. Further research work with RU-486 showed a dose dependent inhibition of human melanoma cell growth. The mechanism of inhibition of cell growth was due to apoptosis and this effect of RU-486 was neither mediated through progesterone receptor nor glucocorticoid receptor. This in-vitro study suggested that melanoma also could be a target for RU-486 action, apart from breast, ovary and prostate cancers.

RU-486 is an abortifacient which is used to terminate early pregnancy. It acts by blocking progesterone receptor. In our earlier study with progesterone, RU-486 was used as a progesterone receptor antagonist to find out the mechanism of progesterone action on melanoma cells. Results indicated that the effect of progesterone was not mediated through progesterone receptor. In the course of experiments, it was observed that RU-486 by itself inhibited mouse melanoma cell growth. Further research work with RU-486 showed a dose dependent inhibition of human melanoma cell growth. The mechanism of inhibition of cell growth was due to apoptosis and this effect of RU-486 was neither mediated through progesterone receptor nor glucocorticoid receptor. This in-vitro study suggested that melanoma also could be a target for RU-486 action, apart from breast, ovary and prostate cancers.

TY - JOUR. T1 - The yeast SIN3 gene product negatively regulates the activity of the human progesterone receptor and positively regulates the activities of GAL4 and the HAP1 activator. AU - Nawaz, Zafar. AU - Baniahmad, Claudia. AU - Burris, Thomas P.. AU - OMalley, Bert W.. AU - Stillman, David J.. AU - TsaiTsaiTsai, Ming Jer. PY - 1994/11/1. Y1 - 1994/11/1. N2 - The activation of gene transcription in eukaryotic organisms is regulated by sequence-specific DNA-binding proteins as well as by non-DNA-binding proteins. In this report we describe the modulatory functions of a non-DNA-binding protein, SIN3 (also known as SDI1, UME4, RPD1, and GAM2) on the transactivation properties of the human progesterone receptor (hPR), GAL4, and the HAPl activator in yeast. Our data suggest that SIN3 is a dual function protein. It negatively regulates the transcriptional activities of hPR-A and hPR-B by affecting the N-terminal activation domain (AFI). SIN3 positively regulates the transcriptional activities of ...

Growing tumors are hypoxic and respond to microenvironmental stress through increased expression of the hypoxia inducible factor-1α (HIF-1α) transcription factor, resulting in an adaptive switch to glycolytic metabolism, angiogenic signaling, survival, and metastasis. HIF-1α expression is associated with tumor resistance to cytotoxic therapy and inferior patient outcomes. Pancreatic cancer is the most hypoxic of all solid tumors and remains refractory to current chemoradiotherapy. We have seen nuclear HIF-1α in 88% of human pancreatic ductal carcinoma but in only 16% of normal pancreas. Stroma adjacent to the pancreatic ductal carcinoma also showed HIF-1α in 43% of cases. We investigated the novel selective HIF-1α inhibitor PX-478 on in vitro and in vivo radiation response of human pancreatic cancer models. Inhibition of HIF-1α by PX-478 increased cell killing by radiation. In mice with Panc-1, CF-PAC-1, or SU.86.86 pancreatic xenografts, concurrent administration of PX-478 potentiated ...

References for Abcams Human Progesterone ELISA Kit (ab108654). Please let us know if you have used this product in your publication

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Toripristone (INN) (developmental code name RU-40555) is a synthetic, steroidal antiglucocorticoid as well as antiprogestogen which was never marketed. It is reported as a potent and highly selective antagonist of the glucocorticoid receptor (GR) (Ki = 2.4 nM), though it also acts as an antagonist of the progesterone receptor (PR). The pharmacological profile of toripristone is said to be very similar to that of mifepristone, except that toripristone does not bind to orosomucoid (α1-acid glycoprotein). The drug has been used to study the hypothalamic-pituitary-adrenal axis and has been used as a radiotracer for the GR. Its INN was given in 1990. Aglepristone Lilopristone Onapristone Telapristone R.A. Hill; H.L.J. Makin; D.N. Kirk; G.M. Murphy (23 May 1991). Dictionary of Steroids. CRC Press. pp. 101-. ISBN 978-0-412-27060-4. https://mednet-communities.net/inn/db/media/docs/p-innlist61.pdf Steiniger, Bjorn; Kniess, Torsten; Bergmann, Ralf; Pietzsch, Jens; Wuest, Frank (2008). Radiolabeled ...

The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single PGR gene residing on chromosome 11q22, it has two main forms, PR-A and PR-B, that differ in their molecular weight. A third, lesser-known isoform, the PR-C, also exists. The PR-B is the positive regulator of the effects of progesterone, while PR-A and PR-C serve to antagonize the effects of PR-B. Progesterone is necessary to induce the progesterone receptors. When no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a structural change that removes the inhibitory action. Progesterone antagonists prevent the structural reconfiguration. After progesterone binds to the receptor, restructuring with dimerization follows and the complex enters the nucleus and binds to DNA. There transcription takes place, resulting in formation ...

There is accumulating evidence to suggest that progesterone plays an essential role in the regulation of growth and differentiation of mammary glands and thus may play a key role in breast cancer. The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (PR-A and PR-B forms). In most cell contexts, the B form functions as a transcriptional activator, whereas the A form functions as a transcriptional inhibitor of steroid hormones. Recently it has been demonstrated that there is differential hormone dependent regulation of the phosphorylation of the A and B forms of the receptor. Treatment of T47D breast cancer cells with progestin agonist increases the phosphorylation of Ser190 and Ser294 with different kinetics. These phosphorylation events may differentially affect the transcriptional activity of the receptor ...

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TY - JOUR. T1 - Mitogen-activated protein kinase regulates nuclear association of human progesterone receptors. AU - Qiu, Ming. AU - Olsen, Abby. AU - Faivre, Emily. AU - Horwitz, Kathryn B.. AU - Lange, Carol A. PY - 2003/4/1. Y1 - 2003/4/1. N2 - Breast cancers often have increased MAPK activity; this pathway may drive breast cancer cell growth by targeting steroid hormone receptors. MAPK phosphorylates human progesterone receptors (PRs) on Ser294, thus regulating several aspects of PR activity. To study the role of PR Ser294 phosphorylation on subcellular distribution, we stably expressed wild-type (wt) or S294A (Ser294 to Ala) PR-B in several cell types. PRs phosphorylated on Ser294 were nuclear. Activation of MAPK induced Ser294 phosphorylation and rapid nuclear translocation of wt, but not S294A, PR-B; both receptors concentrated in the nucleus after progestin treatment. The MAPK kinase inhibitor, U0126, blocked epidermal growth factor but not progestin-induced Ser294 phosphorylation and ...

Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. Mifepristone is also a powerful glucocorticoid receptor antagonist, and has occasionally been used in refractory Cushings Syndrome (due to ectopic/neoplastic ACTH/Cortisol secretion). During early trials, it was known as RU-38486 or simply RU-486, its designation at the Roussel Uclaf company, which designed the drug. The drug was initially made available in France, and other countries then followed-often amid controversy. It is marketed under tradenames Mifegyne, Zacafemyl and Mifeprex. ...

Background: Progesterone receptors play a key role in the development of canine mammary tumours, and recent research has focussed on their possible value as therapeutic targets using antiprogestins. Cloning and sequencing of the progesterone receptor gene has shown that the receptor has two isoforms, A and B, transcribed from a single gene. Experimental studies in human breast cancer suggest that the differential expression of progesterone receptor isoforms has implications for hormone therapy responsiveness. This study examined the effects of the antiprogestin aglepristone on cell proliferation and mRNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20 mg/Kg of aglepristone (n = 22) or vehicle (n = 5) twice before surgery. Results: Formalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor and both isoforms by RT-qPCR and Ki67 antigen labelling. Both total progesterone ...

Background: Progesterone receptors play a key role in the development of canine mammary tumours, and recent research has focussed on their possible value as therapeutic targets using antiprogestins. Cloning and sequencing of the progesterone receptor gene has shown that the receptor has two isoforms, A and B, transcribed from a single gene. Experimental studies in human breast cancer suggest that the differential expression of progesterone receptor isoforms has implications for hormone therapy responsiveness. This study examined the effects of the antiprogestin aglepristone on cell proliferation and mRNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20 mg/Kg of aglepristone (n = 22) or vehicle (n = 5) twice before surgery. Results: Formalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor and both isoforms by RT-qPCR and Ki67 antigen labelling. Both total progesterone ...

MTP Kit is a combination therapy which consists of two active ingredients, termed as Misoprostol and Mifepristone. These two active ingredients belongs to the category of different female hormones, which is useful to terminate the unwanted pregnancy below the 63 days. Mifepristone is a Progesterone antagonist, whereas, Misoprostol is a Prostaglandin analogue. http://bit.ly/2fYVNeA #health #mtpkit […]. ...

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