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https://www.readbyqxmd.com/read/29783894/fulvestrant-in-management-of-hormone-receptor-positive-metastatic-breast-cancer
#1
Maryam Nemati Shafaee, Matthew James Ellis
Fulvestrant is a steroidal selective estrogen receptor degrader that was approved by the US FDA in 2002 for treatment of ER-positive metastatic breast cancer (ER + MBC) post-progression on aromatase inhibitors. In 2016, the label was updated to include endocrine therapy naive ER + MBC. While initially fulvestrant was thought to be equivalent to aromatase inhibitors with monthly dose of 250 mg intramuscular injection, several postmarketing trials challenged this understanding. Subsequently, the recommended dose changed to 500 mg monthly plus loading dose, and this was proven to be superior to anastrozole in efficacy...
May 22, 2018: Future Oncology
https://www.readbyqxmd.com/read/29783185/impact-of-body-mass-index-on-the-efficacy-of-endocrine-therapy-in-patients-with-metastatic-breast-cancer-a-retrospective-two-center-cohort-study
#2
Luwam Zewenghiel, Henrik Lindman, Antonis Valachis
BAKGROUND: The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant. METHODS: A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified...
May 18, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29781326/progression-free-survival-with-endocrine-based-therapies-following-progression-on-non-steroidal-aromatase-inhibitor-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-a-network-meta-analysis
#3
Rajeev Ayyagari, Derek Tang, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, David Chandiwana, Anand A Dalal, Polly Ann Niravath
OBJECTIVE: To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with HR+/HER2- mBC after NSAI progression. DESIGN: network meta-analysis (NMA) Methods: Randomized clinical trials of ETs for HR+/HER2- mBC were identified via a systematic literature review using Medline, EMBASE, Cochrane Library, and key conference proceedings. All trials met the following inclusion criteria: 1) included women with HR+/HER2- mBC, 2) previous treatment with ETs or chemotherapy as first-line therapy, 3) treatment with ET as monotherapy or in combination with targeted therapy, 4) PFS was reported, and 5) published in 2007 (when HER2 testing became standardized) or later...
May 21, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29775928/tributyltin-impaired-reproductive-success-in-female-zebrafish-through-disrupting-oogenesis-reproductive-behaviors-and-serotonin-synthesis
#4
Wei-Yang Xiao, Ying-Wen Li, Qi-Liang Chen, Zhi-Hao Liu
Tributyltin (TBT), an organotin acting as aromatase (Cyp19a1) inhibitor, has been found to disrupt gametogenesis and reproductive behaviors in several fish species. However, few studies addressing the mechanisms underlying the impaired gametogenesis and reproduction have been reported. In this study, female adults of zebrafish (Danio rerio) were continuously exposed to two nominal concentrations of TBT (100 and 500 ng/L, actual concentrations: 90.8 ± 1.3 ng/L and 470.3 ± 2.7 ng/L, respectively) for 28 days...
May 12, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29772457/in-vitro-and-in-vivo-metabolic-investigation-of-the-palbociclib-by-uhplc-q-tof-ms-ms-and-in-silico-toxicity-studies-of-its-metabolites
#5
Balasaheb B Chavan, Shristy Tiwari, Shankar G, Rakesh D Nimbalkar, Prabha Garg, Srinivas R, M V N Kumar Talluri
Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug...
May 14, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29771302/physical-linkage-of-estrogen-receptor-%C3%AE-and-aromatase-in-rat-oligocrine-and-endocrine-actions-of-cns-produced-estrogens
#6
Emiliya M Storman, Nai-Jiang Liu, Martin W Wessendorf, Alan R Gintzler
Rapid-signaling membrane estrogen receptors and aromatase are present throughout the central nervous system (CNS), enabling acute regulation of CNS estrogenic signaling. We previously reported that spinal membrane aromatase (mAro) and membrane estrogen receptor α (mERα) oligomerize (1). Since their organizational relationship would likely influence functions of locally produced estrogens, we quantified the mAro and mERα that are physically associated and non-associated in two functionally different regions of rat CNS - spinal cord, which has predominantly neural functionalities, and hypothalamus, which has both neural and endocrine capabilities...
May 15, 2018: Endocrinology
https://www.readbyqxmd.com/read/29770981/a-dehydrogenase-dual-hydrogen-abstraction-mechanism-promotes-estrogen-biosynthesis-can-we-expand-the-functional-annotation-of-the-aromatase-enzyme
#7
Angelo Spinello, Matic Pavlin, Lorenzo Casalino, Alessandra Magistrato
Cytochromes P450 (CYP450) are involved in the metabolism of exogenous compounds and in the synthesis of signaling molecules. Among the latter, human aromatase (HA) promotes estrogen biosynthesis, being a key pharmacological target against breast cancers. After decades of debate, the interest in gaining a comprehensive picture of HA catalysis has been renewed by the recent discovery that Compound I (Cpd I) is the reactive species of the peculiar aromatization step. Here, we provide for the first time a complete atomic-level picture of all controversial steps of estrogen biosynthesis...
May 17, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29770127/temporal-expression-patterns-of-genes-related-to-sex-steroid-action-in-sexually-dimorphic-nuclei-during-puberty
#8
Moeko Kanaya, Masahiro Morishita, Shinji Tsukahara
Sex steroids play a major role in sexually dimorphic brain development during not only the perinatal period but also the pubertal period. We previously showed that, in male mice, the estrogen receptor-α ( Esr1 ) and aromatase ( Cyp19a1 ) genes are essential to the sexually dimorphic formation of the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), but the estrogen receptor-β ( Esr2 ) gene is not necessary. We also showed that the androgen receptor ( Ar ) gene is essential to the sexually dimorphic formation of the BNSTp...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769550/prenatal-alcohol-exposure-increases-the-susceptibility-to-develop-aggressive-prolactinomas-in-the-pituitary-gland
#9
Shaima Jabbar, Kenneth Reuhl, Dipak K Sarkar
Excess alcohol use is known to promote development of aggressive tumors in various tissues in human patients, but the cause of alcohol promotion of tumor aggressiveness is not clearly understood. We used an animals model of fetal alcohol exposure that is known to promote tumor development and determined if alcohol programs the pituitary to acquire aggressive prolactin-secreting tumors. Our results show that pituitaries of fetal alcohol-exposed rats produced increased levels of intra-pituitary aromatase protein and plasma estrogen, enhanced pituitary tissue growth, and upon estrogen challenge developed prolactin-secreting tumors (prolactinomas) that were hemorrhagic and often penetrated into the surrounding tissue...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769099/circulating-esr1-mutations-at-the-end-of-aromatase-inhibitor-adjuvant-treatment-and-after-relapse-in-breast-cancer-patients
#10
Violette Allouchery, Ludivine Beaussire, Anne Perdrix, David Sefrioui, Laetitia Augusto, Cécile Guillemet, Nasrin Sarafan-Vasseur, Frédéric Di Fiore, Florian Clatot
BACKGROUND: Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. METHODS: This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29765929/gonadotropin-releasing-hormone-agonist-plus-aromatase-inhibitor-in-the-treatment-of-uterine-leiomyoma-in-near-menopause-patient-a-case-series-study
#11
Sanam Moradan
Objectives: There are many drugs for of symptomatic fibroids. Gonadotropin-releasing hormone (GnRH) agonists are the well known drugs. Also, aromatase inhibitors are effective. All published studies surveyed the effect of one of these two drugs. In this study as the first study decided to evaluate the effectiveness of the combination of GnRH agonists + aromatise inhibitor on the uterine fibroids. Methods: A cross-sectional prospective case series study was performed on 10 known cases of uterine fibroids late perimenopause, at least 3 myomas >5 cm, abnormal uterine bleeding and anemia due to fibroids, candidate for hysterectomy, no tendency to surgery...
April 2018: Journal of Menopausal Medicine
https://www.readbyqxmd.com/read/29765553/acquired-resistance-to-everolimus-in-aromatase-inhibitor-resistant-breast-cancer
#12
Mariko Kimura, Toru Hanamura, Kouki Tsuboi, Yosuke Kaneko, Yuri Yamaguchi, Toshifumi Niwa, Kazutaka Narui, Itaru Endo, Shin-Ichi Hayashi
We previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The present study generated everolimus-resistant (EvR) cells from Types 1 and 2 EDR cells following long-term exposure to everolimus in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29758407/synthesis-and-molecular-docking-of-n-n-disubstituted-thiourea-derivatives-as-novel-aromatase-inhibitors
#13
Ratchanok Pingaew, Veda Prachayasittikul, Nuttapat Anuwongcharoen, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul
A three series of thioureas, monothiourea type I (4a-g), 1,4-bisthiourea type II (5a-h) and 1,3-bisthiourea type III (6a-h) were synthesized. Their aromatase inhibitory activities have been evaluated. Interestingly, eight thiourea derivatives (4e, 5f-h, 6d, 6f-h) exhibited the aromatase inhibitory activities with IC50 range of 0.6-10.2 μM. The meta-bisthiourea bearing 4-NO2 group (6f) and 3,5-diCF3 groups (6h) were shown to be the most potent compounds with sub-micromolar IC50 values of 0.8 and 0.6 μM, respectively...
May 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29758382/effects-of-exposure-to-bpf-on-development-and-sexual-differentiation-during-early-life-stages-of-zebrafish-danio-rerio
#14
Qian Yang, Xianhai Yang, Jining Liu, Yingwen Chen, Shubao Shen
Bisphenol F (BPF) has become a predominant bisphenol contaminant in recent years. It has significant estrogenic properties in both in vivo and in vitro studies. We have previously studied the disrupting mechanisms of BPF on the hypothalamic-pituitary-gonadal axis of adult zebrafish. However, the effects of BPF exposure on development and sexual differentiation of zebrafish embryos/larvae remain unclear. To determine the effects of BPF on the critical stage of sex differentiation in zebrafish, zebrafish embryos/larvae were exposed to 1, 10, 100, and 1000 μg/L BPF from fertilization to 60 days post-fertilization (dpf)...
May 11, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29755815/late-endobronchial-pulmonary-metastasis-in-a-patient-with-breast-cancer
#15
İbrahim Güven Çoşğun, Turgut Kaçan, Gül Erten
The lung is a common location for malignant metastases. However, endobronchial metastases from nonpulmonary neoplasms are rare. Metastatic breast cancer usually occurs in 2-3 years of the disease course. A 65-year-old woman visited our hospital for the evaluation of dry cough. The patient had a history of breast cancer, which was treated with modified radical mastectomy and axillary dissection 10 years ago; she was then treated with aromatase inhibitor for 5 years. Chest X-ray revealed right hilum enlargement...
April 2018: Turkish Thoracic Journal
https://www.readbyqxmd.com/read/29755596/phytochemicals-current-strategies-for-treating-breast-cancer
#16
REVIEW
Bridg'ette B Israel, Syreeta L Tilghman, Kitani Parker-Lemieux, Florastina Payton-Stewart
Females with early-stage metastatic, estrogen-dependent breast cancer are generally treated with surgery, radiation and chemotherapy, or with more targeted approaches such as aromatase inhibitors (anastrozole or letrozole) or anti-estrogens (tamoxifen). Despite widespread successful usage of these agents for the treatment of breast cancer, resistance, tumor relapse and metastasis remain the principal causes of mortality for patients with breast cancer. While numerous groups have made major contributions toward an improved understanding of resistance mechanisms, the currently insufficient grasp of the most critical pathways involved in resistance is evident in the inability to adequately treat and drastically improve patient outcomes in females with hormone-refractory breast cancer, including triple negative breast cancer...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29754304/impact-of-high-deductible-insurance-on-adjuvant-hormonal-therapy-use-in-breast-cancer
#17
Christine Y Lu, Fang Zhang, Anita K Wagner, Larissa Nekhlyudov, Craig C Earle, Matthew Callahan, Robert LeCates, Xin Xu, Dennis Ross-Degnan, J Frank Wharam
OBJECTIVE: High-deductible health plans (HDHPs) have become the predominant commercial health insurance arrangement in the US. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS: This controlled quasi-experimental study used claims data (2003-2012) from a large national health insurer...
May 12, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29753248/embryonic-exposure-to-benzo-a-pyrene-inhibits-reproductive-capability-in-adult-female-zebrafish-and-correlation-with-dna-methylation
#18
Dongxu Gao, Jing Lin, Kunlin Ou, Ying Chen, Hongbin Li, Qinhua Dai, Zhenni Yu, Zhenghong Zuo, Chonggang Wang
This study was conducted to investigate the effects of embryonic short-term exposure to benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, on ovarian development and reproductive capability in adult female zebrafish. In 1-year-old fish after embryonic exposure to BaP for 96 h, the gonadosomatic indices and the percentage of mature oocytes were significantly decreased in the 0.5, 5 and 50 nmol/L treatments. The spawned egg number, the fertilization rate and the hatching success were significantly reduced, while the malformation rate of the F1 unexposed larvae were increased...
May 9, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29752687/a-phase-ii-study-evaluating-the-efficacy-of-zoledronic-acid-in-prevention-of-aromatase-inhibitor-associated-musculoskeletal-symptoms-the-zap-trial
#19
Cesar A Santa-Maria, Aditya Bardia, Amanda L Blackford, Claire Snyder, Roisin M Connolly, John H Fetting, Daniel F Hayes, Stacie C Jeter, Robert S Miller, Anne Nguyen, Katie Quinlan, Gary L Rosner, Shannon Slater, Anna Maria Storniolo, Antonio C Wolff, Jane Zorzi, Nora Lynn Henry, Vered Stearns
PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are common adverse events of AIs often leading to drug discontinuation. We initiated a prospective clinical trial to evaluate whether bisphosphonates are associated with reduced incidence of AIMSS. METHODS: In the single-arm trial, the Zoledronic Acid Prophylaxis (ZAP) trial, we compared the incidence of AIMSS against historical controls from the Exemestane and Letrozole Pharmacogenomics (ELPh) trial...
May 11, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29752333/the-endocrinology-of-male-breast-cancer
#20
REVIEW
Ian S Fentiman
Male breast cancer (MBC) is a rare disease but, as a result of epidemiological collaborations, there is now greater clarity concerning endocrine risk factors. The significant rise in global age-standardised mean BMI in men is likely to lead to increases in incidence of maturity-onset diabetes and MBC. The metabolic changes accompanying obesity decrease androgens and sex hormone-binding globulin (SHBG), thereby increasing available oestrogens. The higher rates of MBC in North and Equatorial Africa are largely due to liver damage from endemic bilharziasis and hepatitis B causing elevated oestradiol (E2 ) levels from hepatic conversion of androgen...
June 2018: Endocrine-related Cancer
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