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Michaël R Laurent
An overview of selected papers related to bone published in 2017 is provided. PURPOSE: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. METHODS: A PubMed search using the keyword "bone" and articles published in 2017. RESULTS: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation...
March 15, 2018: Archives of Osteoporosis
Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation with placental hypoxia can result in preeclampsia, a hypertensive disorder of pregnancy. Herein, we characterized the role and regulation of miR-1246, which is markedly induced during human syncytiotrophoblast differentiation. miR-1246 is known to target GSK3β and AXIN2, inhibitors of WNT/β-catenin signaling, which is crucial for placental development, and is predicted to target JARID2, which promotes silencing of developmentally regulated genes...
March 13, 2018: Endocrinology
Irene E G van Hellemond, Ingeborg J H Vriens, Petronella G M Peer, Astrid C P Swinkels, Carolien H Smorenburg, Caroline M Seynaeve, Maurice J C van der Sangen, Judith R Kroep, Hiltje de Graaf, Aafke H Honkoop, Frans L G Erdkamp, Franchette W P J van den Berkmortel, Jos J E M Kitzen, Maaike de Boer, Wïlfred K de Roos, Sabine C Linn, Alexander L T Imholz, Vivianne C G Tjan-Heijnen
Background: Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen. Methods: We identified all patients with chemotherapy-induced ovarian function failure...
December 1, 2017: Journal of the National Cancer Institute
M Cunha-Silva, V N Brito, D B Macedo, D S Bessa, C O Ramos, L G Lima, P S Barroso, I J P Arnhold, D L Segaloff, B B Mendonca, A C Latronico
Testotoxicosis is a rare cause of peripheral precocious puberty in boys caused by constitutively activating mutations of the LHCG receptor. Affected males usually have normal gonadotropin profiles and fertility in their adult life. Here, we described the long-term follow-up of a 24-year-old young man with severe testotoxicosis due to a de novo activating mutation in the third transmembrane helix of the LHCGR (p.Leu457Arg). This patient was treated with different medications, including medroxyprogesterone acetate, ketoconazole, cyproterone acetate and aromatase inhibitor from age 2...
March 12, 2018: Human Reproduction
Yakup Bozkaya, Gökmen Umut Erdem, Nebi Serkan Demirci
Arthralgia, myalgia, paresthesia, reduced bone mineral density, vasomotor side effects including hot flashes and night sweats, genitourinary symptoms including decreased libido, vaginal dryness and dyspareunia are common side effects of aromatase inhibitors. Unlike the common side effects, the information on neurological side effects like hallucination of aromatase inhibitor was limited in literature cases. Herein, we reported a case of hallucination related to anastrozole in a patient with metastatic breast cancer...
January 1, 2018: Journal of Oncology Pharmacy Practice
Tiago Augusto, Georgina Correia-da-Silva, Cecília M P Rodrigues, Natércia Teixeira, Cristina Amaral
Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen-receptor positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired-resistance may develop, leading to tumour relapse. This resistance is thought to be the result of a change in the behavior of ER in these breast cancer cells, presumably by PI3K/Akt pathway enhancement along with alterations in other signalling pathways...
March 12, 2018: Endocrine-related Cancer
G Legendre, L Delbos, E Hudon, N Chabbert-Buffet, S Geoffron, M Sauvan, H Fernandez, P-E Bouet, P Descamps
OBJECTIVE: The objective of this work is to evaluate the place of new treatments in the management of endometriosis outside the context of infertility. METHODS: A review of the literature was conducted by consulting Medline data until July 2017. RESULTS: Dienogest is effective compared to placebo in short term (NP2) and long term (NP4) for the treatment of painful endometriosis. In comparison with GnRH agonists, dienogest is also effective in terms of decreased pain and improved quality of life in non-operated patients (NP2) as well as for recurrence of lesions and symptomatology postoperatively (NP2)...
March 9, 2018: Gynecologie, Obstetrique, Fertilite & Senologie
Kellie A Fay, Daniel L Villeneuve, Joe Swintek, Stephen Edwards, Mark Nelms, Brett R Blackwell, Gerald T Ankley
The U.S. Environmental Protection Agency's ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential apical effects relevant to risk assessors. Thus, efforts are underway to develop AOPs relevant to pathway-specific perturbations detected in ToxCast assays. Previous work identified a 'cytotoxic burst' (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Elena Ongaro, Lorenzo Gerratana, Marika Cinausero, Giacomo Pelizzari, Elena Poletto, Manuela Giangreco, Claudia Andreetta, Stefano Pizzolitto, Carla Di Loreto, Alessandro Marco Minisini, Mauro Mansutti, Stefania Russo, Gianpiero Fasola, Fabio Puglisi
AIM: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. METHODS: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test...
March 12, 2018: Future Oncology
Elie El Rassy, Ziad Bakouny, Tarek Assi, Joseph Kattan
AIM: To determine which of the CDK4/6 inhibitors is the optimal treatment in metastatic luminal breast cancer. MATERIALS & METHODS: A network meta-analysis using the frequentist approach and generalized pairwise modeling was computed. RESULTS: The associations of aromatase inhibitor with ribociclib, palbociclib and abemaciclib were similar in efficacy. Palbociclib-based regimen was associated with significantly lower treatment discontinuation rates compared with the other approved drugs in this indication...
March 12, 2018: Future Oncology
Avi Ben-Haroush, Irit Ben-Aharon, Yechezkel Lande, Benjamin Fisch
BACKGROUND: Controlled ovarian hyperstimulation (COH) followed by oocyte retrieval is a leading option for fertility preservation before chemotherapy, yet this procedure causes excessive serum levels of estradiol (E2), which are often detrimental for cancer patients. Aromatase inhibitors are often used in breast cancer patients during COH to prevent elevated levels of E2. OBJECTIVES: To describe our experience with COH for oocyte cryopreservation in non-breast cancer patients using aromatase inhibitors...
March 2018: Israel Medical Association Journal: IMAJ
Zafer Sahin, Merve Ertas, Barkın Berk, Sevde Nur Biltekin, Leyla Yurttas, Seref Demirayak
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme...
February 27, 2018: Bioorganic & Medicinal Chemistry
Jasmine L Gowarty, Jon D Herrington
A promising drug, palbociclib, received accelerated approval as a first line treatment when used with the aromatase inhibitor, letrozole, for postmenopausal women with hormone receptor positive advanced or metastatic breast cancer. We report a case of a patient who presented with febrile neutropenia, grade 3 stomatitis with lip swelling, periorbital edema, and transaminitis while on palbociclib and verapamil. Labs normalized upon discontinuation of verapamil and our patient was able to continue treatment with palbociclib and letrozole...
January 1, 2018: Journal of Oncology Pharmacy Practice
Kristina Beijer, Maria Jönsson, Siraz Shaik, Daphné Behrens, Björn Brunström, Ingvar Brandt
Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes. We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo...
February 21, 2018: Aquatic Toxicology
Merve Ertas, Zafer Sahin, Barkin Berk, Leyla Yurttas, Sevde N Biltekin, Seref Demirayak
Drugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non-steroidal-type inhibitors. Non-steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition...
March 9, 2018: Archiv der Pharmazie
Katsuhiko Nakatsukasa, Hiroshi Koyama, Yoshimi Ouchi, Kouichi Sakaguchi, Yoshifumi Fujita, Takayuki Matsuda, Makoto Kato, Eiichi Konishi, Tetsuya Taguchi
Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months...
March 8, 2018: Journal of Bone and Mineral Metabolism
Marine de Ciantis, Christelle Faure, Pierre-Etienne Heudel, Olivier Tredan, Christine Rousset-Jablonski
In premenopausal women treated for breast cancer, endocrine therapy combining an aromatase inhibitor (AI) and a gonadotropin-releasing hormone (GnRH) agonist (GA) for ovarian suppression may be indicated in high-risk or in metastatic cancer. AIs are effective in premenopausal women only when ovarian estrogen production is suppressed, a state achievable through the use of GAs. However, a complete suppression sometimes proves elusive. We report here three cases of ovarian suppression failure in premenopausal breast cancer patients who received adjuvant AI+GA...
March 3, 2018: Journal of Gynecology Obstetrics and Human Reproduction
Wei Yang, Gary N Schwartz, Jonathan D Marotti, Vivian Chen, Nicole A Traphagen, Jiang Gui, Todd W Miller
The mTORC1 inhibitor RAD001 (everolimus) is approved for treatment of recurrent/metastatic estrogen receptor (ER)-positive breast cancer in combination with the aromatase inhibitor (AI) exemestane. The benefits of A) continued anti-estrogen therapy for anti-estrogen-resistant disease in the context of mTORC1 inhibition, and B) adjuvant everolimus in combination with anti-estrogen therapy for early-stage disease are being tested clinically, but molecular rationale remains unclear. We hypothesized that mTORC1 inhibition activates the IGF-1R/InsR/IRS-1/2 axis in an ER-dependent manner to drive PI3K/AKT and promote cancer cell survival, implicating ER in survival signaling induced by mTORC1 inhibition...
February 6, 2018: Oncotarget
L Alexandre, F Taillieu, J-B Arlet, A Passeron, A Michon, A-S Bats, J Pouchot, B Ranque
BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare condition characterized by histologically benign "metastatic" smooth muscle tumors, which can affect women with history of uterine surgery. We report the case of a patient with bone metastases of BML. CASE REPORT: A 78-year-old woman who had undergone uterine surgery six years before hospital admission, was diagnosed with large pulmonary and pleural metastases that necessitated surgical removal...
March 1, 2018: La Revue de Médecine Interne
Amanda L Gentry, Susan M Sereika, Frances E Casillo, Mary E Crisafio, Patrick T Donahue, George A Grove, Anna L Marsland, Jennifer C Watt, Catherine M Bender
The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer...
February 28, 2018: Contemporary Clinical Trials
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