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Gerald J Pepe, Adina Maniu, Graham Aberdeen, Terrie J Lynch, Soon Ok Kim, Jerry Nadler, Eugene D Albrecht
We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %)...
October 21, 2016: Endocrine
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
Aya Matsuoka, Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Hiroko Yukawa, Shiho Sakaguchi, Natsuko Tanaka, Asaka Kodera, Mari Kamimura, Yoshihiko Naritaka, Tadao Shimizu
A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Francesco De Logu, Raquel Tonello, Serena Materazzi, Romina Nassini, Camilla Fusi, Elisabetta Coppi, Simone Li Puma, Ilaria M Marone, Laura R Sadofsky, Alyn M Morice, Tommaso Susini, Alessandro Terreni, Gloriano Moneti, Mariarosaria Di Tommaso, Pierangelo Geppetti, Silvia Benemei
Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, since the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of patients, we hypothesized that additional factors may cooperate to induce AIMSS. Here we report that the aromatase substrate androstenedione, unique among several steroid hormones, targeted TRPA1 in peptidergic primary sensory neurons in rodent and human cells expressing the native or recombinant channel...
October 6, 2016: Cancer Research
Anna Kemp-Casey, Elizabeth E Roughead, Christobel Saunders, Frances Boyle, Max Bulsara, David B Preen
AIMS: To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. METHODS: We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 (n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy...
October 14, 2016: Asia-Pacific Journal of Clinical Oncology
Gabriel N Hortobagyi, Salomon M Stemmer, Howard A Burris, Yoon-Sim Yap, Gabe S Sonke, Shani Paluch-Shimon, Mario Campone, Kimberly L Blackwell, Fabrice André, Eric P Winer, Wolfgang Janni, Sunil Verma, Pierfranco Conte, Carlos L Arteaga, David A Cameron, Katarina Petrakova, Lowell L Hart, Cristian Villanueva, Arlene Chan, Erik Jakobsen, Arnd Nusch, Olga Burdaeva, Eva-Maria Grischke, Emilio Alba, Erik Wist, Norbert Marschner, Anne M Favret, Denise Yardley, Thomas Bachelot, Ling-Ming Tseng, Sibel Blau, Fengjuan Xuan, Farida Souami, Michelle Miller, Caroline Germa, Samit Hirawat, Joyce O'Shaughnessy
Background The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease...
October 7, 2016: New England Journal of Medicine
Nelly Mauras, Judith L Ross, Priscila Gagliardi, Y Miles Yu, Jobayer Hossain, Joseph Permuy, Ligeia Damaso, Debbie Merinbaum, Ravinder J Singh, Ximena Gaete, Veronica Mericq
CONTEXT: Growth of short children in puberty is limited by estrogen's effect on epiphyseal fusion. OBJECTIVES: To compare: (1) efficacy and safety of aromatase inhibitors (AIs) vs. GH vs. AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and (2) body composition among groups. DESIGN: Randomized 3 arms open-label comparator Setting: Outpatient clinical research Patients: 76 pubertal boys, mean (SE) age: 14...
October 6, 2016: Journal of Clinical Endocrinology and Metabolism
Hatem Abu Hashim
Orally active aromatase inhibitors (AIs) have gained attention for treatment of infertile women with endometriosis in whom aromatase p450 is aberrantly expressed. This review aimed to critically appraise and summarize the available evidence concerning the use of AIs for management of endometriosis-associated infertility. PubMed was searched to May 2015 with the following key words: endometriosis, infertility and aromatase. Priority was given for randomized controlled trials (RCTs) followed by other study designs...
October 2016: International Journal of Fertility & Sterility
Javier Domingo, Juan A Garcia-Velasco
PURPOSE OF REVIEW: It is necessary to clarify the fertility preservation-related points of concern that often frighten patients or physicians when it comes to deciding about oocyte cryopreservation for fertility preservation, which are often perceived as procedure limitations, are sometimes real and often theoretical and may make the prognosis worse. RECENT FINDINGS: Letrozole added to gonadotrophins for controlled ovarian stimulation is safe when applied to hormone-sensitive cancer patients as it avoids associated high estradiol levels...
September 28, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
Ryutaro Mori, Manabu Futamura, Kasumi Morimitsu, Kazuhiro Yoshida
The appropriate therapy for metastatic breast cancer must be selected based on the immunohistochemical phenotype of the cancer. However, biopsy for metastatic lesions is difficult. We herein report a patient with incidental appendicitis caused by a metastatic breast cancer which was successfully treated with effective therapy chosen based on the pathological diagnosis obtained on resection. The patient was a 56-year-old female with right breast cancer and an immunohistochemical status of estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2 (HER2) (3+), and Ki67 40 %...
December 2016: Surgical Case Reports
Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Takeshi Iwasa, Munkhsaikhan Munkhzaya, Rie Yanagihara, Takako Tokui, Kiyohito Yano, Yiliyasi Mayila, Takeshi Kato, Akira Kuwahara, Sumika Matsui, Minoru Irahara
Hypersecretion of luteinizing hormone (LH) is a common endocrinological finding of polycystic ovary syndrome (PCOS). This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs of 3-week-old female Wistar rats...
September 24, 2016: Endocrine Journal
Li-Ming Zhao, Hai-Shan Jin, Jinzhong Liu, Todd C Skaar, Joseph Ipe, Wei Lv, David A Flockhart, Mark Cushman
The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the potent AI letrozole were incorporated into the lead compound (norendoxifen) to afford a series of new dual AI/SERM agents based on a symmetrical diphenylmethylene substructure that eliminates the problem of E,Z isomerization encountered with norendoxifen-based AI/SERMs...
November 1, 2016: Bioorganic & Medicinal Chemistry
Carolin C Hack, Peter A Fasching, Tanja Fehm, Johann de Waal, Mahdi Rezai, Bernd Baier, Gerold Baake, Hans-Christian Kolberg, Martin Guggenberger, Mathias Warm, Nadia Harbeck, Rachel Wuerstlein, Jörg-Uwe Deuker, Peter Dall, Barbara Richter, Grischa Wachsmann, Cosima Brucker, Jan W Siebers, Nikos Fersis, Thomas Kuhn, Christopher Wolf, Hans-Walter Vollert, Georg-Peter Breitbach, Wolfgang Janni, Robert Landthaler, Andreas Kohls, Daniela Rezek, Thomas Noesslet, Gunnar Fischer, Stefan Henschen, Thomas Praetz, Volker Heyl, Thorsten Kühn, Thomas Krauss, Christoph Thomssen, Andre Hohn, Hans Tesch, Christoph Mundhenke, Alexander Hein, Claudia Rauh, Christian M Bayer, Adib Jacob, Katja Schmidt, Erik Belleville, Peyman Hadji, Sara Y Brucker, Diethelm Wallwiener, Sherko Kümmel, Matthias W Beckmann, Daniela Paepke
Background Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer...
September 14, 2016: Integrative Cancer Therapies
Jinyong Liu, Tin-Chiu Li, Jing Wang, Wei Wang, Zhen Hou, Jiayin Liu
OBJECTIVE: To evaluate the impact of ovarian stimulation on the outcome of intrauterine insemination (IUI). DESIGN: Retrospective analysis. SETTING: A single university-based centre. POPULATION: A total of 5109 couples with 8893 cycles. METHODS: The outcome of IUI with different protocols for ovarian stimulation was examined. MAIN OUTCOME MEASURES: The live birth rate (LBR), twin pregnancy rate and ovarian hyperstimulation syndrome (OHSS)...
September 2016: BJOG: An International Journal of Obstetrics and Gynaecology
Connor G O'Leary, Haley Ellis, Michaela Higgins
PURPOSE OF REVIEW: The risk of relapse associated with oestrogen receptor-positive early breast cancer persists for at least 15 years after diagnosis. Several large clinical trials have examined extended adjuvant endocrine therapy. RECENT FINDINGS: The MA.17 trial demonstrated improved disease-free survival (DFS) with use of letrozole for 5 years after some years of tamoxifen and an overall survival advantage for this approach in women with node-positive oestrogen receptor-positive cancer at diagnosis...
November 2016: Current Opinion in Oncology
Elena Andreucci, Paola Francica, Antony Fearns, Lesley-Ann Martin, Paola Chiarugi, Clare M Isacke, Andrea Morandi
The majority of breast cancers are estrogen receptor positive (ER+). Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER+ breast cancers. However, AI resistance remains a major challenge. We have demonstrated previously that increased GDNF/RET signaling in ER+ breast cancers promotes AI resistance. Here we investigated the efficacy of different small molecule RET kinase inhibitors, sunitinib, cabozantinib, NVP-BBT594 and NVP-AST487, and the potential of combining a RET inhibitor with the AI letrozole in ER+ breast cancers...
September 2, 2016: Oncotarget
C Yavas, G Yavas, H Toy, O Ata
Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively...
September 5, 2016: Human & Experimental Toxicology
Ahmed A M Abdel-Hamid, Yaser Mesbah, Mona F M Soliman
Letrozole (LTZ), one of the ovulation induction medications, is increasingly prescribed in various gynaecological conditions. Previous studies have demonstrated its potential hazardous effect on the ovarian surface epithelium (OSE) as well as on tubal epithelial cells (TEC). However, it is not clear whether this effect could be reversed by LTZ cessation. Therefore, the objective of our study was to investigate the effect of stoppage of LTZ on these cells after 12 cycles of ovarian stimulation. A total of 54 Sprague Dawley rats were used in this study, divided equally into control, LTZ12 and CES12 groups (received saline, 12 cycles of LTZ and 12 cycles of cessation post-LTZ12 respectively)...
August 2016: International Journal of Experimental Pathology
Xue-Jing Yi, Tamer T El-Idreesy, Taha M A Eldebss, Ahmad M Farag, Mohamed M Abdulla, Shaimaa A Hassan, Yahia N Mabkhot
A new series derived from 4-(2-chloroacetyl)-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one was synthesized, characterized and its pharmacological activity toward aromatase enzyme inhibition was screened and compared to the reference native ligand letrozole. The most active compound of the series was 16, showing IC50 value of 0.0023 ± 0.0002 μm compared to letrozole with IC50 of 0.0028 ± 0.0006 μm. In addition, compounds 26 and 36 exhibit good inhibition activities close to letrozole with IC50 values 0...
August 27, 2016: Chemical Biology & Drug Design
Andrea Estrada, Alison M Boyce, Beth A Brillante, Lori C Guthrie, Rachel I Gafni, Michael T Collins
OBJECTIVE: McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. DESIGN: Retrospective cohort analysis. METHODS: Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls...
November 2016: European Journal of Endocrinology
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