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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/28522306/the-effects-of-chronic-testosterone-administration-on-body-weight-food-intake-and-adipose-tissue-are-changed-by-estrogen-treatment-in-female-rats
#5
Takeshi Iwasa, Toshiya Matsuzaki, Kiyohito Yano, Rie Yanagihara, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Yiliyasi Mayila, Akira Kuwahara, Minoru Irahara
In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats...
May 17, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28521442/mrna-expression-of-steroidogenic-enzymes-steroid-hormone-receptors-and-their-coregulators-in-gastric-cancer
#6
Bartosz Adam Frycz, Dawid Murawa, Maciej Borejsza-Wysocki, Mateusz Wichtowski, Arkadiusz Spychała, Ryszard Marciniak, Paweł Murawa, Michał Drews, Paweł Piotr Jagodziński
Epidemiological and experimental findings suggest that the development of gastric cancer (GC) is regulated by steroid hormones. In postmenopausal women and older men, the majority of steroid hormones are produced locally in peripheral tissue through the enzymatic conversion of steroid precursors. Therefore, using reverse transcription-quantitative polymerase chain reaction analysis, the mRNA expression of genes encoding steroidogenic enzymes, including steroid sulfatase (STS), hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), 17β-hydroxysteroid dehydrogenase type 7 and aromatase (CYP19A1), was investigated in primary tumoral and adjacent healthy gastric mucosa from 60 patients with GC...
May 2017: Oncology Letters
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
#7
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
#8
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
#9
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
#10
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/28506466/impaired-steroidogenesis-in-the-testis-of-leptin-deficient-mice-ob-ob
#11
Fabiane Ferreira Martins, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
The obesity and its comorbidities, including resistance to leptin, impacts the reproductive function. Testes express leptin receptors in the germ cells and Leydig cells. Then, leptin-deficient animals are obese and infertile. We aimed to evaluate the structure and steroidogenic pathway of the testis of deficient leptin mice. Three months old male C57BL/6 mice (wild-type, WT) and deficient leptin (ob/ob) mice had their testes dissected and prepared for analyses. Compared to the WT group, the ob/ob group showed a greater body mass with smaller testes, and alterations in the germinative epithelium: fewer spermatogonia, spermatocytes, and spermatids...
May 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28502742/seasonal-changes-of-androgen-receptor-estrogen-receptors-and-aromatase-expression-in-the-hippocampus-of-the-wild-male-ground-squirrels-citellus-dauricus-brandt
#12
Fengwei Zhang, Yu Wang, Wentao Han, Junjie Wang, Haolin Zhang, Xia Sheng, Zhengrong Yuan, Qiang Weng, Yingying Han
The wild ground squirrel is a typical seasonal breeder whose annual life cycle can be roughly divided into the breeding season, the post-breeding season and hibernation. Our previous study has reported the seasonal changes in the expressions of androgen receptor (AR), estrogen receptors α and β (ERα and ERβ), and aromatase cytochrome P450 (P450arom) in the hypothalamus of male wild ground squirrels. To further seek evidence of seasonal expression of steroid hormone receptors and steroid hormone synthases in other brain regions, we investigated the protein and mRNA expressions of AR, ERα, ERβ and P450arom in the hippocampus of the male wild ground squirrels during these different reproductive periods...
May 11, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28501702/brown-adipose-tissue-activation-by-rutin-ameliorates-polycystic-ovary-syndrome-in-rat
#13
Tao Hu, Xiaoxue Yuan, Rongcai Ye, Huiqiao Zhou, Jun Lin, Chuanhai Zhang, Hanlin Zhang, Gang Wei, Meng Dong, Yuanyuan Huang, Wonchung Lim, Qingsong Liu, Hyuek Jong Lee, Wanzhu Jin
Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28501695/expression-of-aromatase-and-estrogen-receptors-in-lumbar-motoneurons-of-mice
#14
Ying-Xiao Ji, Mei Zhao, Ya-Ling Liu, Li-Sha Chen, Peng-Li Hao, Can Sun
Estrogen exerts protective roles in amyotrophic lateral sclerosis (ALS). However, the expression of aromatase (ARO) and estrogen receptors (ERs) in the motoneurons of spinal cord, has not yet been elucidated. By immunohistochemistry, we found that ARO and ERs were present in the ventral horn of adult mice lumbar spinal cord, and colocalized with SMI-32, a motoneuron specific marker. Within motoneurons, we observed that ARO is detected primarily in the cytoplasm, with fewer ARO in the nucleus; ERα and ERβ mainly localized in the nucleus with less in the cytoplasm; while GPR30 is located in soma and processes...
May 10, 2017: Neuroscience Letters
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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