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Mifepristone

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https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#1
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28421651/self-management-of-first-trimester-medical-termination-of-pregnancy-a-qualitative-study-of-women-s-experiences
#2
Carrie Purcell, Sharon Cameron, Julia Lawton, Anna Glasier, Jeni Harden
OBJECTIVE: To explore the experiences of women in Scotland who return home to complete medical termination of pregnancy (TOP) ≤63 days of gestation, after being administered with mifepristone and misoprostol at an NHS TOP clinic. DESIGN: Qualitative interview study. SETTING: One National Health Service health board (administrative) area in Scotland. POPULATION OR SAMPLE: Women in Scotland who had undergone medical TOP ≤63 days, and self-managed passing the pregnancy at home; recruited from three clinics in on NHS health board area between January and July 2014...
April 19, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28420496/the-value-of-hysteroscopic-management-of-cesarean-scar-pregnancy-a-report-of-44-cases
#3
Ying Pan, Mu-Biao Liu
OBJECTIVE: With the incidence of cesarean scar pregnancy (CSP) rising, the reports of serious adverse outcomes of it have increased gradually. The management of CSP remains an inadequately explored clinical field, and there is no consensus on it presently. The present study was performed to investigate the efficacy and safety of operative hysteroscopy in the diagnosis and treatment of CSP. MATERIALS AND METHODS: Forty-four patients with CSP underwent operative hysteroscopy for removal of scar ectopic pregnancy in our institution...
April 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28414589/progesterone-decreases-in-vitro-indoleamine-2-3-dioxygenase-expression-in-dendritic-and-cd4-cells-from-maternal-fetal-interface-of-rats
#4
Pedro Kastein Faria da Cunha Bianchi, Rafael Magdanelo Leandro, Aline Nayara Poscai, Tulio Yoshinaga, Patrícia Orlandini Gonçalez, José Roberto Kfoury Junior
PROBLEM: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation...
April 17, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28412963/posttranslationally-modified-progesterone-receptors-direct-ligand-specific-expression-of-breast-cancer-stem-cell-associated-gene-programs
#5
Todd P Knutson, Thu H Truong, Shihong Ma, Nicholas J Brady, Megan E Sullivan, Ganesh Raj, Kathryn L Schwertfeger, Carol A Lange
BACKGROUND: Estrogen and progesterone are potent breast mitogens. In addition to steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and progesterone receptor (PR) actions via posttranslational events. Protein kinases commonly activated in breast cancers phosphorylate steroid hormone receptors (SRs) and profoundly impact their activities. METHODS: To better understand the role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs in 209 human breast tumors represented on 2754 individual tissue spots within a tissue microarray and assayed the regulation of this site in human tumor explants cultured ex vivo...
April 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28407578/a-peek-into-the-drug-development-scenario-of-endometriosis-a-systematic-review
#6
REVIEW
Luxitaa Goenka, Melvin George, Maitrayee Sen
PURPOSE AND OBJECTIVE: Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis...
April 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28391165/metapristone-suppresses-non-small-cell-lung-cancer-proliferation-and-metastasis-via-modulating-ras-raf-mek-mapk-signaling-pathway
#7
Guirong Zheng, Zhichun Shen, Hongning Chen, Jian Liu, Kai Jiang, Lulu Fan, Lee Jia, Jingwei Shao
BACKGROUND: Metastasis is the key phase of cancer progression that characterizes a more advanced stage and a poorer prognosis. The majority of cancer fatalities occur as a consequence of metastasis. OBJECTIVE: Mifepristone (RU486), a chemical abortifacient, has recently been used in clinical trials for psychotic depression and cancer chemotherapy. As the most predominant biological active metabolite of mifepristone, metapristone is being developed as a novel cancer metastasis chemopreventive agent by us...
April 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28376402/metapristone-ru486-derivative-inhibits-cell-proliferation-and-migration-as-melanoma-metastatic-chemopreventive-agent
#8
Ning Zheng, Jiahang Chen, Weiqun Liu, Jichuang Wang, Jian Liu, Lee Jia
Uncontrolled cell proliferation and metastasis are the two well-known manifestations of melanoma. We hypothesized that metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486), had a dual function to fight cancer. In the present study, our findings clearly demonstrated that metapristone had modest cytostatic effect in melanoma cells. Metapristone inhibited cell viability and induced both early and late apoptosis in B16F10 and A375 cells in a time- and concentrate-dependent manner...
April 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28376177/progesterone-receptor-isoform-ratio-a-breast-cancer-prognostic-and-predictive-factor-for-antiprogestin-responsiveness
#9
Paola A Rojas, María May, Gonzalo R Sequeira, Andrés Elia, Michelle Alvarez, Paula Martínez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M Perou, Alfredo Molinolo, Luz Gibbons, Martin C Abba, Hugo Gass, Claudia Lanari
Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28368581/the-identification-of-the-clinical-candidate-r-1-4-fluorophenyl-6-1-methyl-1h-pyrazol-4-yl-sulfonyl-4-4a-5-6-7-8-hexahydro-1h-pyrazolo-3-4-g-isoquinolin-4a-yl-4-trifluoromethyl-pyridin-2-yl-methanone-cort125134-a-selective-glucocorticoid-receptor-gr-antagonist
#10
Hazel J Hunt, Joseph K Belanoff, Iain Walters, Benoit Gourdet, Jennifer Thomas, Naomi Barton, John Unitt, Timothy Phillips, Denise Swift, Emily Eaton
The non-selective glucocorticoid receptor (GR) antagonist, mifepristone, has been approved in the USA for the treatment of selected patients with Cushing's syndrome. Whilst this drug is highly effective, lack of selectivity for GR leads to unwanted side effects in some patients. Optimization of the previously described fused azadecalin series of selective GR antagonists led to the identification of CORT125134, which is currently being evaluated in a Phase 2 clinical study in patients with Cushing's syndrome...
April 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28351055/comparison-of-the-induction-to-delivery-interval-in-terminations-of-pregnancy-with-or-without-dilapan-s%C3%A2
#11
Marie Vincienne, Olivia Anselem, Anne Gaelle Cordier, Camille Le Ray, Vassilis Tsatsaris, Alexandra Benachi, François Goffinet
OBJECTIVE: In France, terminations of pregnancy (TOP) for medical reasons beyond the second trimester use mifepristone and misoprostol. We sought to determine the effectiveness of Dilapan-S®, an osmotic cervical dilator, in shortening the induction-to-delivery interval (IDI). MATERIALS AND METHODS: This retrospective study of TOP in 2010-2012 compared the results from 2 hospitals with different TOP protocols starting at 16 weeks' gestation, one (164 women) with and one (106) without Dilapan-S®...
March 29, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28337228/evaluation-of-efficacy-and-safety-of-dan-e-fukang-soft-extract-in-the-treatment-of-endometriosis-a-meta-analysis-of-39-randomized-controlled-trials-enrolling-5442-patients
#12
REVIEW
Yantao Li, Te Li, Shilin Song
Objective. To systematically evaluate the efficacy and safety of Dan'e-fukang soft extract in endometriosis treatment. Method. PubMed, CNKI, Wanfang Database, VIP, SinoMed, and Cochrane Library were searched. Randomized controlled trials (RCTs) comparing the efficacy of Dan'e-fukang soft extract and conventional western medicines for endometriosis treatment were included. The data were extracted independently by two people and analyzed using RevMan 5.2.0 software. The relative risk (RR) and mean difference (MD) with 95% confidence intervals were considered as effective outcome indicators...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28317327/a-research-agenda-for-moving-early-medical-pregnancy-termination-over-the-counter
#13
REVIEW
Nathalie Kapp, Daniel Grossman, Emily Jackson, Laura Castleman, Dalia Brahmi
Given the overall safety profile and increasing availability of medical pregnancy termination drugs, we asked: would the mifepristone-misoprostol regimen for medical termination at ≤10 weeks gestation meet U.S. FDA regulatory criteria for over-the-counter (OTC) approval, and if not, what are the present research gaps? We conducted a literature review of consumer behaviors necessary for a successful OTC application for medical termination ≤10 weeks and identified crucial research gaps. If we were to embark on a development program for OTC or more generally, self-use of medical termination, the critical elements missing are the label comprehension, self -selection and actual use studies...
March 19, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28303569/efficacy-and-safety-of-mifepristone-buccal-misoprostol-for-early-medical-abortion-in-an-australian-clinical-setting
#14
Philip Goldstone, Clara Walker, Katherine Hawtin
BACKGROUND: In 2014, a composite pack containing mifepristone-buccal misoprostol, indicated for use to 63 days gestation replaced the existing regimen for early medical abortion (EMA) in Australia. AIMS: To provide updated efficacy and safety information for the use of mifepristone-buccal misoprostol for EMA in Australia, and assess the effect of patient age and gestational age on efficacy. MATERIALS AND METHODS: Observational cohort study of 15 008 women attending one of 16 Marie Stopes International clinics in Australia for an EMA (gestational age ≤ 63 days) between 1 March 2013 and 30 September 2015...
March 17, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28300476/ovarian-steroid-hormones-modulate-the-expression-of-progesterone-receptors-and-histone-acetylation-patterns-in-uterine-leiomyoma-cells
#15
Gabriela Dos Santos Sant'Anna, Ilma Simoni Brum, Gisele Branchini, Lolita Schneider Pizzolato, Edison Capp, Helena von Eye Corleta
Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium...
March 16, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28292452/sometimes-you-do-get-a-second-chance-emergency-contraception-for-adolescents
#16
REVIEW
Ellen S Rome, Veronica Issac
Unplanned or unintended pregnancy remains a significant challenge for adolescents; many teens who plan ahead but opt not to choose long-acting reversible contraceptive methods have high failure rates with condom usage, oral contraceptives, and other less long-acting methods. Emergency contraception (EC) remains a necessity for those adolescents seeking a second chance to prevent the unintended consequences of unplanned sexual activity. At present, 5 postcoital methods remain available as EC globally: intrauterine devices, ulipristal acetate, a selective progesterone modulator, mifepristone; levonorgestrel, and ethinyl estradiol plus levonorgestrel or norgestrel (rarely used now that progestin only methods are more readily available)...
April 2017: Pediatric Clinics of North America
https://www.readbyqxmd.com/read/28288649/medical-termination-of-pregnancy-in-general-practice-in-australia-a-descriptive-interpretive-qualitative-study
#17
Angela J Dawson, Rachel Nicolls, Deborah Bateson, Anna Doab, Jane Estoesta, Ann Brassil, Elizabeth A Sullivan
BACKGROUND: Australian Government approval in 2012 for the use of mifepristone and misoprostol for medical termination of pregnancy (MTOP) allows general practitioners (GPs) to provide early gestation abortion in primary care settings. However, uptake of the MTOP provision by GPs appears to be low and the reasons for this have been unclear. This study investigated the provision of and referral for MTOP by GPs. METHODS: We undertook descriptive-interpretive qualitative research and selected participants for diversity using a matrix...
March 14, 2017: Reproductive Health
https://www.readbyqxmd.com/read/28272244/management-of-patients-with-placenta-accreta-in-association-with-fever-following-vaginal-delivery
#18
Liuying Zhong, Dunjin Chen, Mei Zhong, Yutian He, Chunhong Su
This study aims to analyze the clinical characteristics and to manage patients with retained placenta left in situ accompanied by fever following vaginal delivery.Twenty-one patients with retained placenta in association with fever following vaginal delivery were enrolled and managed at the maternity department of our university hospital between 2012 and 2014.All patients had risk factors for development of placenta accreta: previous cesarean sections (4/21), previous curettage (15/21), or uterine malformations (7/21)...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28263819/cortisol-plays-a-role-in-the-high-environmental-ammonia-associated-suppression-of-the-immune-response-in-zebrafish
#19
A F Gonçalves, J V Neves, J Coimbra, P Rodrigues, M M Vijayan, J M Wilson
Exposure to high environmental ammonia (HEA) levels increases the vulnerability of fishes to parasitic, viral and bacterial diseases. We tested the hypothesis that elevated plasma cortisol levels play a role in the HEA-mediated immunosuppression in fishes. To this end, we tested the effect of exogenous cortisol treatment on the lipopolysaccharide (LPS)-induced immune response in zebrafish (Danio rerio). Also, to test whether glucocorticoid receptor (GR) signaling is involved in HEA-mediated immunosuppression, zebrafish were treated with mifepristone, a GR antagonist, and the LPS-induced immune response assessed after HEA exposure...
March 2, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28238310/-repeat-induced-abortion-a-multicenter-study-on-medical-abortions-in-france-in-2014
#20
M Opatowski, F Bardy, P David, A Dunbavand, M-J Saurel-Cubizolles
OBJECTIVES: To describe the social characteristics of women seeking a medical abortion, and the conditions of that abortion, according to whether they had one or more previous induced abortions. METHODS: An observational study was carried out in 11 French units in 2013-2014, among women 18 years or older. A self-administered questionnaire on the abortion context and social situation was given to them, as well as a diary to record the pain level for each of five days following the mifepristone intake...
January 2017: Gynecologie, Obstetrique, Fertilite & Senologie
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