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https://www.readbyqxmd.com/read/28535537/triggering-of-suicidal-erythrocyte-death-by-exemestane
#1
Abdulla Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The steroidal aromatase inactivator exemestane blocks estrogen biosynthesis and is thus employed for the prevention and treatment of breast cancer. Exemestane is in part effective by stimulation of suicidal cell death or apoptosis. Side effects of exemestane treatment include anemia. At least in theory, exemestane induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
May 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534527/role-of-the-ugt2b17-deletion-in-exemestane-pharmacogenetics
#2
S Luo, G Chen, C Truica, C C Baird, K Leitzel, P Lazarus
Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of breast cancer. The major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β-D-glucuronide (17β-DHE-Gluc) by UGT2B17. The aim of the present study was to determine the effects of UGT2B17 copy number variation on the levels of urinary and plasma 17β-DHE-Gluc and 17β-DHE in patients taking EXE. Ninety-six post-menopausal Caucasian breast cancer patients with ER+ breast tumors taking 25 mg EXE daily were recruited into this study...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28529550/hormonoresistance-in-advanced-breast-cancer-a-new-revolution-in-endocrine-therapy
#3
REVIEW
Paule Augereau, Anne Patsouris, Emmanuelle Bourbouloux, Carole Gourmelon, Sophie Abadie Lacourtoisie, Dominique Berton Rigaud, Patrick Soulié, Jean Sebastien Frenel, Mario Campone
Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28526959/adjuvant-tamoxifen-but-not-aromatase-inhibitor-therapy-decreases-serum-levels-of-the-wnt-inhibitor-dickkopf-1-while-not-affecting-sclerostin-in-breast-cancer-patients
#4
Andy Göbel, Jan D Kuhlmann, Theresa Link, Pauline Wimberger, Andrew J Browne, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner
PURPOSE: Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive...
May 19, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28515111/racial%C3%A2-differences-in-adjuvant-endocrine-therapy-use-and-discontinuation-in-association-with-mortality-among-medicare-breast-cancer-patients-by-receptor-status
#5
Albert J Farias, Xianglin L Du
BACKGROUND: There are racial disparities in breast cancer mortality. Our purpose was to determine whether racial/ethnic differences in use and discontinuation of AET differed by hormone receptor status and whether discontinuation was associated with mortality. METHODS: We conducted a retrospective cohort study with SEER/Medicare dataset of women age 65 years or older diagnosed with stage I-III breast cancer in Medicare Part-D from 2007-2009, stratified by hormone receptor status...
May 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28512028/evaluation-of-synthesized-coumarin-derivatives-on-aromatase-inhibitory-activity
#6
Yuki Yamaguchi, Naozumi Nishizono, Daisuke Kobayashi, Teruki Yoshimura, Keiji Wada, Kazuaki Oda
In women across the world, the most common type of cancer is breast cancer. Among medical treatments, endocrine therapy based on aromatase inhibitors (AI) is expected to be effective against not only post-menopausal but also pre-menopausal breast cancer. In this study, we examined the structure-activity relationship between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives with a substituent at position 3 and coumarin derivatives with a substituent at position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values 30...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28510222/primary-ectopic-breast-cancer-of-the-vulva-treated-with-local-excision-of-the-vulva-and-sentinel-lymph-node-biopsy-a-case-report
#7
Takayuki Ishigaki, Yasuo Toriumi, Ryouko Nosaka, Rei Kudou, Yoshimi Imawari, Makiko Kamio, Hiroko Nogi, Hisashi Shioya, Hiroshi Takeyama
Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28506988/dmrt1-induces-the-male-pathway-in-a-turtle-with-temperature-dependent-sex-determination
#8
Chutian Ge, Jian Ye, Haiyan Zhang, Yi Zhang, Wei Sun, Yapeng Sang, Blanche Capel, Guoying Qian
The molecular mechanism underlying temperature-dependent sex determination (TSD) has been a long-standing mystery; in particular, the thermo-sensitive genetic triggers for gonadal sex differentiation are largely unknown. Here, we characterized a conserved DM domain gene, Dmrt1, in the red-eared slider turtle Trachemys scripta (T. scripta), which exhibits TSD. We found that Dmrt1 has a temperature-dependent, sexually dimorphic expression pattern, preceding gonadal sex differentiation, and is capable of responding rapidly to temperature shifts and aromatase inhibitor treatment...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28494403/her2-status-predicts-for-upfront-ai-benefit-a%C3%A2-trans-aiog-meta-analysis-of-12-129-patients-from%C3%A2-atac-big-1-98-and-team-with-centrally-determined-her2
#9
John M S Bartlett, Ikhlaaq Ahmed, Meredith M Regan, Ivana Sestak, Elizabeth A Mallon, Patrizia Dell'Orto, Beat Thürlimann, Caroline Seynaeve, Hein Putter, Cornelis J H Van de Velde, Cassandra L Brookes, John F Forbes, Giuseppe Viale, Jack Cuzick, Mitchell Dowsett, Daniel W Rea
BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. METHODS: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs...
May 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28491147/a-clinical-guide-to-the-management-of-genitourinary-symptoms-in-breast-cancer-survivors-on-endocrine-therapy
#10
REVIEW
Mariana S Sousa, Michelle Peate, Sherin Jarvis, Martha Hickey, Michael Friedlander
There is increasing attention and concern about managing the adverse effects of adjuvant endocrine therapy for women with early breast cancer as the side effects of therapy influence compliance and can impair quality of life (QoL). Most side effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are directly related to estrogen deprivation, and the symptoms are similar to those experienced during natural menopause but appear to be more severe than that seen in the general population. Prolonged estrogen deprivation may lead to atrophy of the vulva, vagina, lower urinary tract and supporting pelvic structures, resulting in a range of genitourinary symptoms that can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of QoL...
April 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28489882/preparation-of-a-novel-antiserum-to-aromatase-with-high-affinity-and-specificity-its-clinicopathological-significance-on-breast-cancer-tissue
#11
Naoki Kanomata, Shiro Matsuura, Tsunehisa Nomura, Junichi Kurebayashi, Taisuke Mori, Jo Kitawaki, Takuya Moriya
Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87...
2017: PloS One
https://www.readbyqxmd.com/read/28489562/incidence-of-menopausal-symptoms-in-postmenopausal-breast-cancer-patients-treated-with-aromatase-inhibitors
#12
Hong Dongsheng, Bi Ling, Zhou Jun, Tong Ying Hui, Zhao Qingwei, Chen Jing, Lu Xiaoyang
Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to evaluate the occurrence of menopausal symptoms in breast cancer patients receiving the AI therapy. Patients treated with AIs had an increased risk of all-grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14-1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and insomnia in patients receiving AIs was 30...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488183/palbociclib-a-review-in-hr-positive-her2-negative-advanced-or-metastatic-breast-cancer
#13
REVIEW
Esther S Kim, Lesley J Scott
Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates...
May 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28487654/the-association-of-cyp19a1-variation-with-circulating-estradiol-and-aromatase-inhibitor-outcome-can-cyp19a1-variants-be-used-to-predict-treatment-efficacy
#14
REVIEW
Dylan M Glubb, Tracy A O'Mara, Jannah Shamsani, Amanda B Spurdle
After menopause, estradiol is primarily synthesized in peripheral tissues by the enzyme aromatase, encoded by CYP19A1. CYP19A1 variation associates with circulating estradiol in postmenopausal women and this variation is best represented by the intronic variant rs727479. This variation appears to have pleiotropic effects as it also associates with endometrial cancer risk. Indeed, estradiol plays an important role in the development of breast and endometrial cancer. Aromatase inhibitor (AI) drugs are used in the treatment of both diseases, however, response rates for AIs are low and there is currently no way to identify breast or endometrial cancer patients who are more likely to receive a clinical benefit...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28487215/micturition-dysfunction-in-four-month-old-ovariectomized-rats-effects-of-testosterone-replacement
#15
Sandra M Bonilla-Becerra, Mariana G de Oliveira, Fabiano B Calmasini, Julio A Rojas-Moscoso, Angelina Zanesco, Edson Antunes
AIMS: Androgen deficiency has been implicated in urological complications of postmenopausal women. This study examined the effects of testosterone replacements on the lower urinary tract dysfunction in 4-month old ovariectomized (OVX) rats. MAIN METHODS: Sprague-Dawley female rats were OVX bilaterally. Three months later, rats received single intramuscular injections of testosterone undecanoate. Cystometric study, and bladder and urethra smooth muscle reactivities were evaluated...
May 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/28469437/predicting-adherence-to-aromatase-inhibitor-therapy-among-breast-cancer-survivors-an-application-of-the-protection-motivation-theory
#16
Monita Karmakar, Sharrel L Pinto, Timothy R Jordan, Iman Mohamed, Monica Holiday-Goodman
The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI) therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66) on the scale. Nearly 4 in 10 survivors (38%) were non-adherent...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28467729/long-term-follow-up-of-the-intergroup-exemestane-study
#17
James P Morden, Isabel Alvarez, Gianfilippo Bertelli, Alan S Coates, Robert Coleman, Lesley Fallowfield, Jacek Jassem, Stephen Jones, Lucy Kilburn, Per E Lønning, Olaf Ortmann, Claire Snowdon, Cornelis van de Velde, Jørn Andersen, Lucia Del Mastro, David Dodwell, Stig Holmberg, Hanna Nicholas, Robert Paridaens, Judith M Bliss, R Charles Coombes
Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy...
May 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28464211/osteoporosis-therapy-and-outcomes-for-postmenopausal-patients-with-hormone-receptor-positive-breast-cancer-ncic-ctg-ma-27
#18
Allan Lipton, Judith-Anne W Chapman, Kim Leitzel, Ashwani Garg, Kathleen I Pritchard, James N Ingle, G Thomas Budd, Matthew J Ellis, George W Sledge, Manuela Rabaglio, Lei Han, Catherine R Elliott, Lois E Shepherd, Paul E Goss, Suhail M Ali
BACKGROUND: Breast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self-reported osteoporosis and osteoporosis therapy (OPT) on outcomes. METHODS: The MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event-free survival (EFS), and the secondary outcome was distant disease-free survival (DDFS)...
May 2, 2017: Cancer
https://www.readbyqxmd.com/read/28462402/letrozole-gnrh-antagonist-stimulation-protocol-in-poor-ovarian-responders-undergoing-intracytoplasmic-sperm-injection-cycles-an-rct
#19
Mahbod Ebrahimi, Firouzeh Akbari-Asbagh, Mojgan Ghalandar-Attar
BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. OBJECTIVE: The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection...
February 2017: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28460681/identification-and-expression-of-cytochrome-p450-genes-in-the-chinese-giant-salamander-andrias-davidianus
#20
Qiaomu Hu, Hanbing Xiao, Haifeng Tian, Yan Meng
Cytochrome P450 (cyp) genes play vital roles in biological processes, including in metabolism of endogenous and exogenous compounds. Exogenous hormone influences on gene expression that leads to disruption of gonad development have been studied in several species, but whether exogenous hormones affect cyp genes that show sexually dimorphic expression remains to be determined. Here, we identified and characterized cyp genes from the widely-cultured Chinese giant salamander Andrias davidianus. We obtained 20 cyp genes including 11 genes with complete sequences...
June 2017: Theriogenology
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