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https://www.readbyqxmd.com/read/28324268/a-phase-ii-study-of-combined-ridaforolimus-and-dalotuzumab-compared-with-exemestane-in-patients-with-estrogen-receptor-positive-breast-cancer
#1
José Baselga, Serafin M Morales, Ahmad Awada, Joanne L Blum, Antoinette R Tan, Marianne Ewertz, Javier Cortes, Beverly Moy, Kathryn J Ruddy, Tufia Haddad, Eva M Ciruelos, Peter Vuylsteke, Scot Ebbinghaus, Ellie Im, Lamar Eaton, Kumudu Pathiraja, Christine Gause, David Mauro, Mary Beth Jones, Hope S Rugo
PURPOSE: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). METHODS: This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857)...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28324066/hippocampal-aromatization-modulates-spatial-memory-and-characteristics-of-the-synaptic-membrane-in-the-male-zebra-finch
#2
David J Bailey, Yekaterina V Makeyeva, Elizabeth R Paitel, Alyssa L Pedersen, Angel T Hon, Jordan A Gunderson, Colin J Saldanha
The estrogen-synthesizing enzyme aromatase is abundant at the synapse in the zebra finch hippocampus (HP) and its inhibition impairs spatial memory function. To more fully test the role of local estradiol (E2) synthesis in memory, the HP of adult male zebra finches was exposed to either control pellets or those containing the aromatase inhibitor ATD, ATD and E2, ATD and the G protein-coupled estrogen receptor (GPER) agonist G1, or the antagonist G15 alone. Birds were tested for spatial memory acquisition and performance, and HP levels of the postsynaptic protein PSD95 were measured...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320984/investigation-of-antiaromatase-activity-using-hepatic-microsomes-of-nile-tilapia-oreochromis-niloticus
#3
Tanongsak Sassa-Deepaeng, Wasana Chaisri, Surachai Pikulkaew, Siriporn Okonogi
Microsomal aromatase enzymes of humans and rats have been used in antiaromatase assays, but enzyme activity is species-specific. The current study extracted hepatic microsomes of Nile tilapia (Oreochromis niloticus) to investigate and compare the antiaromatase activity of chrysin, quercetin, and quercitrin. This activity was evaluated using a dibenzylfluorescein (DBF) assay. Results revealed that the age and body weight of Nile tilapia affected the yield of extracted microsomes. Extraction of hepatic microsomes of Nile tilapia was most effective when using a reaction medium with a pH of 8...
March 19, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28319725/antiestrogen-use-in-breast-cancer-patients-reduces-the-risk-of-subsequent-lung-cancer-a-population-based-study
#4
Sung-Chao Chu, Chia-Jung Hsieh, Tso-Fu Wang, Mun-Kun Hong, Tang-Yuan Chu
BACKGROUND: There is accumulating epidemiological and preclinical evidence that estrogen might be a driver of lung cancer. Breast cancer survivors can offer a unique patient cohort to examine the effect of antiestrogen therapy on lung cancer carcinogenesis because many of these women would have received long-term selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) as adjuvant treatment. Our hypothesis is that estrogens play a role in lung cancer development, and that antiestrogen therapy would affect the incidence of subsequent lung cancer among breast cancer survivors...
March 17, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28288389/ovarian-ablation-for-premenopausal-breast-cancer-a-review-of-treatment-considerations-and-the-impact-of-premature-menopause
#5
REVIEW
Melica Nourmoussavi, Gary Pansegrau, Jason Popesku, Geoffrey L Hammond, Janice S Kwon, Mark S Carey
Historically, ovarian ablation (OA) was used as therapy for women with recurrent hormone-receptor-positive (HRP) premenopausal breast cancer. With the publication of the SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) randomized trials, there is considerable interest in OA as an adjuvant treatment, either in combination with tamoxifen or an aromatase inhibitor (AI). Thus, we have reviewed current guidelines and key studies on this important topic and have highlighted the relevant biological and pharmacological aspects of the various endocrine therapies...
February 22, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28286987/endometriosis-after-menopause-physiopathology-and-management-of-an-uncommon-condition
#6
I Streuli, H Gaitzsch, J-M Wenger, P Petignat
Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause...
April 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28285644/effects-of-transdermal-testosterone-gel-or-an-aromatase-inhibitor-on-serum-concentration-and-pulsatility-of-growth-hormone-in-older-men-with-age-related-low-testosterone
#7
Jenny Pena Dias, Johannes D Veldhuis, Olga Carlson, Michelle Shardell, Chee W Chia, Denise Melvin, Josephine M Egan, Shehzad Basaria
Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. OBJECTIVE: This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone...
April 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28283903/detection-of-esr1-mutations-in-plasma-and-tumors-from-metastatic-breast-cancer-patients-using-next-generation-sequencing
#8
Takehiro Yanagawa, Naofumi Kagara, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations. METHODS: Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients...
March 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28283467/responsiveness-of-brca1-and-trp53-deficiency-induced-mammary-preneoplasia-to-selective-estrogen-modulators-versus-an-aromatase-inhibitor-in-mus-musculus
#9
Sahar J Alothman, Weisheng Wang, David S Goerlitz, Md Islam, Xiaogang Zhong, Archana Kishore, Redha I Azhar, Bhaskar V Kallakury, Priscilla A Furth
An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 (Brca1) gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 (Trp53) haploinsufficiency (10-16/cohort). The proportion of unexposed control mice demonstrating mammary preneoplasia at age 6 months was highest in Brca1(fl11/fl11/Cre/p53-/+) (54%) mice followed by Brca1(WT/fl11/Cre/p53-/+) mice (30%)...
March 10, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28281842/opportunities-and-challenges-of-long-term-anti-estrogenic-adjuvant-therapy-treatment-forever-or-intermittently
#10
Poulomi Bhattacharya, Balkees Abderrahman, V Craig Jordan
Extended adjuvant (5-10 years) therapy targeted to the estrogen receptor (ER) has significantly decreased mortality from breast cancer (BC). Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops. Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy...
April 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28275510/aromatase-inhibitors-induced-autoimmune-disorders-in-patients-with-breast-cancer-a-review
#11
REVIEW
George Zarkavelis, Aristomenes Kollas, Eleftherios Kampletsas, Vasilis Vasiliou, Evripides Kaltsonoudis, Alexandros Drosos, Hussein Khaled, Nicholas Pavlidis
Subacute cutaneous lupus erythematosus (SCLE) is characterized by particular cutaneous manifestations such as non-scaring plaques mainly in sunlight exposed parts of the body along with specific serum autoantibodies (i.e. antinuclear antibodies (ANA), Ro/SSa, La/SSb). It is considered either idiopathic or drug induced. The role of chemotherapeutic agents in causing SCLE has been investigated with the taxanes being the most common anticancer agents. However, recent data emerging point toward antiestrogen therapies as a causative factor not only for SCLE but also for a variety of autoimmune disorders...
September 2016: Journal of Advanced Research
https://www.readbyqxmd.com/read/28274582/estrogen-receptor-agonists-antagonists-in-breast-cancer-therapy-a-critical-review
#12
REVIEW
A Jameera Begam, S Jubie, M J Nanjan
Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer...
February 23, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28273868/pharmacological-potential-and-synthetic-approaches-of-imidazo-4-5-b-pyridine-and-imidazo-4-5-c-pyridine-derivatives
#13
REVIEW
Malwina Krause, Henryk Foks, Katarzyna Gobis
The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABAA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc...
March 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28267392/bone-density-screening-in-postmenopausal-women-with-early-stage-breast-cancer-treated-with-aromatase-inhibitors
#14
Jamie Stratton, Xin Hu, Pamela R Soulos, Amy J Davidoff, Lajos Pusztai, Cary P Gross, Sarah S Mougalian
PURPOSE: In postmenopausal women with breast cancer treated with aromatase inhibitors (AIs), most expert panels advise baseline bone mineral density testing with a dual-energy x-ray absorptiometry (DXA) scan repeated every 1 to 2 years. How often this recommendation is followed is unclear. METHODS: We performed a retrospective analysis of women with stage I to III breast cancer who started AI therapy from January 1, 2008, to December 31, 2010, with follow-up through December 31, 2012, by using the SEER-Medicare database...
March 7, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28259297/management-of-aromatase-inhibitor-induced-musculoskeletal-symptoms-in-postmenopausal-early-breast-cancer-a-systematic-review-and-meta-analysis
#15
REVIEW
Kate Roberts, Kirsty Rickett, Ristan Greer, Natasha Woodward
Aromatase Inhibitors (AI) are widely used for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. AI are often associated with significant joint and muscular symptoms; symptoms that are commonly referred to as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). AIMSS adversely impacts health-related quality of life of many patients, and reduces AI compliance. Although there are informal practice recommendations, the limited current level of evidence for management of AIMSS for breast cancer patients on aromatase inhibitors has made development of formal guidelines challenging, and remains an unmet need...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28257758/cognition-in-female-rats-after-blocking-conversion-of-androgens-to-estrogens
#16
George T Taylor, Francesca M Manzella, Jacob Huffman, Omar H Cabrera, Jessica Hoffman
Women and non-human females have surprisingly high levels of circulating testosterone, yet the effects of androgens on non-reproductive behaviors, including cognition, of females are not well characterized. The current project used an aromatase inhibitor, letrozole, to block conversion of androgens to estrogens. Adult female rats were ovariectomized and administered either vehicle only, testosterone propionate only (400μg/kg, TP only), letrozole only (1mg/kg, Letro only), or the combination of letrozole and testosterone (TP+Letro) over 4weeks...
March 12, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28255310/binding-mode-of-triazole-derivatives-as-aromatase-inhibitors-based-on-docking-protein-ligand-interaction-fingerprinting-and-molecular-dynamics-simulation-studies
#17
Ayyub Mojaddami, Amirhossein Sakhteman, Masood Fereidoonnezhad, Zeinab Faghih, Atena Najdian, Soghra Khabnadideh, Hossein Sadeghpour, Zahra Rezaei
Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures...
February 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28253566/bilateral-salpingo-oophorectomy-compared-to-gonadotropin-releasing-hormone-agonists-in-premenopausal-hormone-receptor-positive-metastatic-breast-cancer-patients-treated-with-aromatase-inhibitors
#18
Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim
Purpose: Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO). Materials and Methods: We retrospectively analyzed data of 66 premenopausal patients with HR-positive, HER2-negative recurrent and metastatic breast cancer (MBC) who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015...
February 27, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28252426/adjuvant-hormonal-therapy-as-a-cause-of-bone-loss-in-patients-with-breast-cancer-review-of-literature
#19
N Khachidze, E Giorgadze, M Tsagareli
Adjuvant (hormonal) therapy is the main method of treatment after surgery in hormone (estrogen and/or progesterone) positive breast cancer patients. The goal of above mentioned treatment is to reduce or block the level of estrogen and progesterone. ultiple clinical trials have revealed that hormonal therapy in breast cancer patients affect bone mineral density (BMD). Authors have analyzed data obtained from several clinical trials conducted in several countries (including Georgia). The final conclusion is that selective estrogen receptor modulators (SERMs) have negative effect on BMD in pre-menopausal women and aromatase inhibitors (anastrozole, letrozole, exemestane) are associated with significant bone loss in post-menopausal women...
January 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28251491/extended-endocrine-therapy-is-5%C3%A2-years-enough
#20
REVIEW
Manali A Bhave, N Lynn Henry
PURPOSE OF REVIEW: Women with hormone receptor (HR)-positive breast cancer remain at risk for cancer recurrence for decades. In this review, we address recent data regarding the benefits and risks of extended endocrine therapy. RECENT FINDINGS: Ten years of treatment with either tamoxifen or an aromatase inhibitor resulted in superior disease-free survival compared to 5 years of treatment. However, there are risks associated with extended therapy with either class of medication...
March 2017: Current Oncology Reports
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