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Aromatase inhibitors

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https://www.readbyqxmd.com/read/28637041/the-effects-of-fungicides-on-human-3%C3%AE-hydroxysteroid-dehydrogenase-1-and-aromatase-in-human-placental-cell-line-jeg-3
#1
Shuyan Cao, Leping Ye, Ying Wu, Baiping Mao, Lanlan Chen, Xiudi Wang, Ping Huang, Ying Su, Ren-Shan Ge
Placenta secretes a large amount of progesterone and estradiol, which are critical for maintaining pregnancy. In human placenta, 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) catalyzes pregnenolone to form progesterone, and aromatase (CYP19A1) catalyzes testosterone into estradiol. Fungicides display antifungal activities and are widely used to prevent fungal infections in agricultural plants. These chemicals include azoles, such as tebuconazole (TEB), triadimefon (TRI), and vinclozolin (VCZ) or organotins, such as tributyltin (TBT) and tetrabutyltin (TTBT)...
June 22, 2017: Pharmacology
https://www.readbyqxmd.com/read/28635978/vaginal-testosterone-for-management-of-aromatase-inhibitor-related-sexual-dysfunction-an-integrative-review
#2
Emily A Lemke, Lydia T Madsen, Joyce E Dains
PROBLEM IDENTIFICATION: Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including vaginal atrophy, as opposed to postmenopausal women and women treated with tamoxifen (Nolvadex®). Vaginal testosterone could be an alternative to estrogen, which is contraindicated in this population.
. LITERATURE SEARCH: A systematic review was completed by searching PubMed and Scopus databases...
May 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#3
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28632237/auricular-point-acupressure-to-manage-aromatase-inhibitor-induced-arthralgia-in-postmenopausal-breast-cancer-survivors-a-pilot-study
#4
Chao Hsing Yeh, Wei-Chun Lin, Lorna Kwai-Ping Suen, Na-Jin Park, Lisa J Wood, G J van Londen, Dana Howard Bovbjerg
PURPOSE/OBJECTIVES: To assess the feasibility of auricular point acupressure to manage aromatase inhibitor-induced arthralgia.
. DESIGN: Wait list control design.
. SETTING: Outpatient clinics and oncology center.
. SAMPLE: 20 women with aromatase inhibitor-induced arthralgia.
. METHODS: After baseline data were collected, participants waited one month before they received acupressure once per week for four weeks at a convenient time...
July 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28631236/use-of-ctx-i-and-pinp-as-bone-turnover-markers-national-bone-health-alliance-recommendations-to-standardize-sample-handling-and-patient-preparation-to-reduce-pre-analytical-variability
#5
P Szulc, K Naylor, N R Hoyle, R Eastell, E T Leary
N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen are the reference standards for bone turnover markers for monitoring osteoporosis treatment. We provide recommendations for standardized sample handling and encompassing aspects of preanalytical variability to improve the reproductibility of their measurements, their reliability, and clinical interpretation. The International Osteoporosis Foundation and International Federation of Clinical Chemistry bone turnover marker standards working group have identified N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) in the blood to be the international reference standards for bone turnover markers for the prediction of fracture risk and monitoring of osteoporosis treatment...
June 19, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28626628/assessing-fracture-risk-in-early-stage-breast-cancer-patients-treated-with-aromatase-inhibitors-an-enhanced-screening-approach-incorporating-trabecular-bone-score
#6
Veronica Mariotti, David B Page, Oksana Davydov, Didier Hans, Clifford A Hudis, Sujata Patil, Siddharth Kunte, Monica Girotra, Azeez Farooki, Monica N Fornier
INTRODUCTION: Aromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA)...
June 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/28626481/quantum-mechanical-molecular-mechanical-and-docking-study-of-the-novel-analogues-based-on-hybridization-of-common-pharmacophores-as-potential-anti-breast-cancer-agents
#7
Parvin Asadi, Ghadamali Khodarahmi, Hossein Farrokhpour, Farshid Hassanzadeh, Lotfollah Saghaei
In an attempt to identify some new potential leads as anti-breast cancer agents, novel hybrid compounds were designed by molecular hybridization approach. These derivatives were structurally derived from hybrid benzofuran-imidazole and quinazolinone derivatives, which had shown good cytotoxicity against the breast cancer cell line (MCF-7). Since aromatase enzyme (CYP19) is highly expressed in the MCF-7 cell line, the binding of these novel hybrid compounds to aromatase was investigated using the docking method...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28622580/combating-breast-cancer-with-non-steroidal-aromatase-inhibitors-nsais-understanding-the-chemico-biological-interactions-through-comparative-sar-qsar-study
#8
REVIEW
Nilanjan Adhikari, Sk Abdul Amin, Achintya Saha, Tarun Jha
It is a challenging task to design target-specific and less toxic non-steroidal aromatase inhibitors (NSAIs) though the modeling studies for designing anti-aromatase molecules have been continuing for more than two decades to fight the dreaded estrogen-dependent breast cancer. In this article, different validated QSAR models are developed and analyzed to understand important physicochemical and structural parameters modulating the aromatase inhibitory activity of NSAIs. Physicochemical properties such as molar refractivity and dipole moment are found to be the most important parameters for controlling aromatase inhibition...
May 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28615284/tcl1a-snps-and-estrogen-mediated-toll-like-receptor-myd88-dependent-nf-%C3%AE%C2%BAb-activation-snp-and-serm-dependent-modification-of-inflammation-and-immune-response
#9
Ming-Fen Ho, James N Ingle, Tim Bongartz, Krishna R Kalari, Paul E Goss, Lois E Shepherd, Taisei Mushiroda, Michiaki Kubo, Liewei Wang, Richard M Weinshilboum
In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy of breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol (E2), but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the "downstream" expression of a series of cytokines and chemokines and had a striking effect on NF-κB transcriptional activity...
June 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28614542/use-of-anastrozole-in-the-chemoprevention-and-treatment-of-breast-cancer-a-literature-review
#10
Maria da Conceição Barros-Oliveira, Danylo Rafhael Costa-Silva, Danielle Benigno de Andrade, Umbelina Soares Borges, Cléciton Braga Tavares, Rafael Soares Borges, Janaína de Moraes Silva, Benedito Borges da Silva
Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment...
April 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28612226/iris-study-a-phase-ii-study-of-the-steroid-sulfatase-inhibitor-irosustat-when-added-to-an-aromatase-inhibitor-in-er-positive-breast-cancer-patients
#11
Carlo Palmieri, Rob C Stein, Xinxue Liu, Emma Hudson, Hanna Nicholas, Hironobu Sasano, Fouzia Guestini, Chris Holcombe, Sophie Barrett, Laura Kenny, Sadie Reed, Adrian Lim, Larry Hayward, Sacha Howell, R Charles Coombes
PURPOSE: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. EXPERIMENTAL DESIGN: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled...
June 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28611039/chemoprevention-uptake-among-women-with-atypical-hyperplasia-and-lobular-and-ductal-carcinoma-in-situ
#12
Meghna S Trivedi, Austin M Coe, Alejandro Vanegas, Rita Kukafka, Katherine Crew
Women with atypical hyperplasia (AH) and lobular or ductal carcinoma in situ (LCIS/DCIS) are at increased risk of developing invasive breast cancer. Chemoprevention with selective estrogen receptor modulators or aromatase inhibitors can reduce breast cancer risk; however, uptake is estimated to be less than 15% in these populations. We sought to determine which factors are associated with chemoprevention uptake in a population of women with AH, LCIS, and DCIS. Women diagnosed with AH/LCIS/DCIS between 2007 and 2015 without a history of invasive breast cancer were identified (n=1719)...
June 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28610873/williams-syndrome-transcription-factor-wstf-acts-as-an-activator-of-estrogen-receptor-signaling-in-breast-cancer-cells-and-the-effect-can-be-abrogated-by-1%C3%AE-25-dihydroxyvitamin-d3
#13
Johan Lundqvist, Tove Kirkegaard, Anne-Vibeke Laenkholm, Anne Katrine Duun-Henriksen, Martin Bak, David Feldman, Anne E Lykkesfeldt
A majority of estrogen receptor positive (ER+) breast cancers are growth stimulated by estrogens. The ability to inhibit the ER signaling pathway is therefore of critical importance in the current treatment of ER+ breast cancers. It has been reported that 1α,25-dihydroxyvitamin D3 down-regulates the expression of the CYP19A1 gene, encoding the aromatase enzyme that catalyzes the synthesis of estradiol. Furthermore, 1α,25-dihydroxyvitamin D3 has also been reported to down-regulate the expression of estrogen receptor α (ERα), the main mediator of ER signaling...
June 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28603632/exemestane-potency-is-unchanged-by-common-nonsynonymous-polymorphisms-in-cyp19a1-results-of-a-novel-anti-aromatase-activity-assay-examining-exemestane-and-its-derivatives
#14
Amity Peterson, Zuping Xia, Gang Chen, Philip Lazarus
Exemestane (EXE) treats estrogen receptor positive (ER+) breast cancer in postmenopausal women by inhibiting the estrogen-synthesizing cytochrome P450 CYP19A1. Variability in the severity and incidence of side effects as well as overall drug efficacy may be partially explained by genetic factors, including nonsynonymous variation in CYP19A1, also known as aromatase. The present study identified phase I EXE metabolites in human liver microsomes (HLM) and investigated mechanisms that may alter the extent of systemic estrogen deprivation in EXE-treated women with breast cancer, including whether functional polymorphisms in aromatase cause differential inhibition by EXE and whether EXE metabolites possess anti-aromatase activity...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28592202/pharmacogenetics-and-aromatase-inhibitor-induced-side-effects-in-breast-cancer-patients
#15
Valentina Sini, Andrea Botticelli, Gianluigi Lunardi, Stefania Gori, Paolo Marchetti
This paper reviews genetic variations mainly related to the onset of adverse events during aromatase inhibitors in early breast cancer. Genetic variability could occur at different steps. The analysis included studies that involved breast cancer patients, treated with an aromatase inhibitor, genotyped for CYP19A1 and/or CYP17A1 and/or CYP27B1 and/or TCLA1, and/or RANK/RANKL/OPG and/or ESR1/ESR2, and assessed for toxicity profile. Twenty-two articles were included for the analysis. Three studies evaluated outcomes and adverse events; 19 studies assessed only side effects...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28590445/surface-modification-of-carbonate-apatite-nanoparticles-enhances-delivery-and-cytotoxicity-of-gemcitabine-and-anastrozole-in-breast-cancer-cells
#16
Fitya Syarifa Mozar, Ezharul Hoque Chowdhury
pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer cells. However, physical and chemical properties of drug molecules appeared to affect their interactions with CA, with hydrophillic drug so far exhibiting better binding affinity and cellular uptakes compared to hydrophobic drugs...
June 7, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28590310/medical-management-of-endometriosis
#17
Saima Rafique, Alan H Decherney
Endometriosis is a chronic medical condition that affects around 6% to 10% of reproductive age women. Pelvic pain, dysmenorrhea, and infertility are the most common presenting symptoms. The disease is characterized by estrogen-dependent growth of the endometrial glands and stroma outside the endometrial cavity. The diagnosis requires a high degree of suspicion and can be only confirmed on histopathology. Treatment includes medical and surgical options. Both hormonal and nonhormonal medical options are available and are tried at first with a goal to control pain and stop the growth of the endometriotic lesions...
June 5, 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28589380/persistence-with-denosumab-therapy-in-women-affected-by-osteoporosis-with-fragility-fractures-a-multicenter-observational-real-practice-study-in-italy
#18
S Migliaccio, D Francomano, E Romagnoli, C Marocco, R Fornari, G Resmini, A Buffa, G Di Pietro, S Corvaglia, F Gimigliano, A Moretti, A de Sire, N Malavolta, A Lenzi, E A Greco, G Iolascon
BACKGROUND: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. AIM: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. MATERIAL/SUBJECTS AND METHODS: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy...
June 6, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28585619/-palbociclib-combinations-as-new-therapeutic-strategies-in-the-treatment-of-hr-her2-advanced-breast-cancer
#19
Katalin Boér
Until recently, the only endocrine agents used to treat HR+/HER2- advanced breast cancers were tamoxifen, aromatase inhibitors and fulvestrant, although a substantial proportion of patients relapse on these standard therapies. Intensive research has been conducted to develop new strategies to overcome endocrine resistance and to enhance the efficacy of endocrine treatments by combining hormone therapy with other targeted treatment approaches. The development of selective CDK4/6 inhibitors and the introduction of palbociclib, the first molecule in this class in clinical practice, represent an important step in the treatment of HR+ advanced breast cancer...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28578791/letrozole-an-aromatase-inhibitor-reduces-post-peak-age-related-regression-of-rooster-reproductive-performance
#20
Emad Abdulgabbar Ali, Mahdi Zhandi, Armin Towhidi, Mojtaba Zaghari, Mahdi Ansari, Mojtaba Najafi, Hamid Deldar
This study was designed to evaluate orally administrated Letrozole (Lz) on reproductive performance, plasma testosterone and estradiol concentrations and relative abundance of mRNA of GnRH, FSH and LH in roosters. Ross 308 roosters (n=32) that were 40-weeks of age were individually housed and received a basal standard diet supplemented different amounts of capsulated Lz [0 (Lz-0), 0.5 (Lz-0.5), 1 (Lz-1) or 1.5 (Lz-1.5), mg Lz/bird/day] for 12 weeks. Sperm quality variables and plasma testosterone and estradiol concentrations were assessed from the first to the tenth week of the treatment period...
May 27, 2017: Animal Reproduction Science
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