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https://www.readbyqxmd.com/read/29128965/abemaciclib-first-global-approval
#1
Esther S Kim
Abemaciclib (Verzenio™) is an orally administered inhibitor of cyclin-dependent kinases 4 and 6 that is being developed by Eli Lilly and Company. Abemaciclib has been approved in the USA for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, in combination with fulvestrant in women with disease progression following endocrine therapy, and as monotherapy in adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting...
November 11, 2017: Drugs
https://www.readbyqxmd.com/read/29122702/estrogenic-effects-following-larval-exposure-to-the-putative-anti-estrogen-fulvestrant-in-the-fathead-minnow-pimephales-promelas
#2
Jonathan M Ali, Michael T Palandri, Alex T Kallenbach, Edwin Chavez, Jonathan Ramirez, Sathaporn Onanong, Daniel D Snow, Alan S Kolok
The objective of the present study was to investigate the consequences of early-life exposure to fulvestrant on estrogenic gene expression in fathead minnow larvae. To address this objective, fathead minnow larvae were exposed to fulvestrant (ICI 182,780) during the window of sexual differentiation between 0 to 30 days post-hatch (dph). The four treatment groups in this study included: filtered water controls (never exposed), solvent controls (ethanol 0.01%), and nominally low (0.10 μg/L) and high (10.0 μg/L) doses of fulvestrant...
November 6, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29106989/gonadal-hormones-affect-alcohol-drinking-but-not-cue-yohimbine-induced-alcohol-seeking-in-male-and-female-rats
#3
Megan L Bertholomey, Mary M Torregrossa
Alcohol use disorder (AUD) is a chronic, relapsing disease characterized by maladaptive patterns of alcohol drinking and seeking. Though sex differences exist in the etiology of AUD, much remains to be elucidated concerning the mechanisms underlying sex-related vulnerability to developing excessive alcohol-motivated behavior. While a large body of evidence points to an important role of circulating gonadal hormones in mediating cocaine reinforcement, findings are less consistent with respect to ethanol. Critically, the effects of gonadal hormones on the reinstatement of ethanol seeking, a model of "craving"-like behavior that reveals pronounced sex differences, has not yet been examined...
October 26, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29103175/efficacy-and-safety-in-older-patient-subsets-in-studies-of-endocrine-monotherapy-versus-combination-therapy-in-patients-with-hr-her2-%C3%A2-advanced-breast-cancer-a-review
#4
REVIEW
Rachel A Freedman, Sara M Tolaney
PURPOSE: Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population. METHODS: We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer treated with ET ± targeted agents...
November 4, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29100902/effect-of-estrogen-on-prostaglandin-synthetase-in-bovine-oviduct-smooth-muscle
#5
Na Huang, Caiyun Wang, Nan Zhang, Wei Mao, Bo Liu, Yuan Shen, Yu Gao, Yi Zhao, Jinshan Cao
Gamete and embryo transport is an important function of the oviduct. This type of transport involves both smooth muscle contraction and epithelial cell secretions, and the former is mediated by prostaglandins (PGs) and their receptors. Our objective was to study the regulation of prostaglandin synthetase (prostaglandin-endoperoxide synthase-1 (PTGS1), prostaglandin-endoperoxide synthase-2 (PTGS2), mPGES-1, mPGES-2, cPGES, and PGFS) by estradiol (E2) in bovine oviduct smooth muscle. Prostaglandin synthetase mRNA and protein expression were investigated using real-time RT-PCR and Western blot analyses, respectively...
October 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29100043/treatment-landscape-of-advanced-breast-cancer-patients-with-hormone-receptor-positive-her2-negative-tumors-data-from-the-german-praegnant-breast-cancer-registry
#6
Andreas D Hartkopf, Jens Huober, Bernhard Volz, Naiba Nabieva, Florin-Andrei Taran, Judith Schwitulla, Friedrich Overkamp, Hans-Christian Kolberg, Peyman Hadji, Hans Tesch, Lothar Häberle, Johannes Ettl, Michael P Lux, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Matthias W Beckmann, Erik Belleville, Pauline Wimberger, Carsten Hielscher, Matthias Geberth, Nikos Fersis, Wolfgang Abenhardt, Christian Kurbacher, Rachel Wuerstlein, Christoph Thomssen, Michael Untch, Peter A Fasching, Wolfgang Janni, Tanja N Fehm, Diethelm Wallwiener, Sara Y Brucker, Andreas Schneeweiss
PURPOSE: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). METHODS: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use...
October 26, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29095648/factors-associated-with-prolonged-time-to-treatment-failure-with-fulvestrant-500%C3%A2-mg-in-patients-with-postmenopausal-estrogen-receptor-positive-advanced-breast-cancer-a-subgroup-analysis-of-the-jbcrg-c06-safari-study
#7
Hidetoshi Kawaguchi, Norikazu Masuda, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno
OBJECTIVE: The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this subgroup analysis was to further examine data from the Safari study, focusing on ER+ and human epidermal growth factor receptor-negative (HER2-) cases...
November 2, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29079660/dual-mtor-kinases-mln0128-inhibitor-sensitizes-hr-her2-breast-cancer-patient-derived-xenografts-to-trastuzumab-or-fulvestrant
#8
Pei-Yin Hsu, Victoria Shang Wu, Noriko Kanaya, Karineh Petrossian, Hang-Kai Hsu, Duc Nguyen, Daniel Schmolze, Masaya Kai, Chun-Yu Liu, Hannah Lu, Peiguo Chu, Courtney A Vito, Laura Kruper, Joanne Mortimer, Shiuan Chen
PURPOSE: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized. EXPERIMENTAL DESIGN: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis...
October 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29078070/endocrine-disruptors-affect-larval-zebrafish-behavior-testing-potential-mechanisms-and-comparisons-of-behavioral-sensitivity-to-alternative-biomarkers
#9
Thomas W K Fraser, Abdolrahman Khezri, Anna M Lewandowska-Sabat, Theodore Henry, Erik Ropstad
Larval zebrafish (Danio rerio) are a tool for assessing endocrine disruption during early development. Here, we investigated the extent to which a simple light/dark behavioral test at five days post fertilization could compliment current methods within the field. We exposed fertilized embryos to hormones (17β-estradiol, testosterone, dihydrotestosterone, 11-ketotestosterone, thyroxine, triiodothyronine, progesterone, and hydrocortisone) and other relevant compounds (17α ethinylestradiol, bisphenol A, bisphenol S, nonylphenol, flutamide, nilutamide, linuron, drospirenone, potassium perchlorate, mifepristone, and fadrozole) to screen for behavioral effects between 96 and 118h post fertilization (hpf)...
October 6, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29066685/-indoleamine-2-3-dioxygenase-activity-during-fulvestrant-therapy-for-aromatase-inhibitor-resistant-metastatic-breast-cancer
#10
Kenichi Sakurai, Shigeru Fujisaki, Hitomi Kubota, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)for breast cancer patients between different clinical stages and patient ages. IDO activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high performance liquid chromatography(HPLC). Serum Trp/Kyn levels in Stage IV breast cancer patients were lower than in patients at other stages. Serum Trp/Kyn levels of breast cancer patients over the age of 70 years were lower than in patients under the age of 69 years...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29029116/upregulation-of-irs1-enhances-igf1-response-in-y537s-and-d538g-esr1-mutant-breast-cancer-cells
#11
Zheqi Li, Kevin M Levine, Amir Bahreini, Peilu Wang, David Chu, Ben Ho Park, Steffi Oesterreich, Adrian V Lee
Increased evidence suggests that somatic mutations in the ligand binding domain of estrogen receptor (ERα/ESR1) are critical mediators of endocrine-resistant breast cancer progression. Insulin-like growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis, and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28978178/anthropometric-clinical-and-molecular-determinants-of-treatment-outcomes-in-postmenopausal-hormone-receptor-positive-metastatic-breast-cancer-patients-treated-with-fulvestrant-results-from-a-real-word-setting
#12
Laura Pizzuti, Clara Natoli, Teresa Gamucci, Mariella Mauri, Domenico Sergi, Luigi Di Lauro, Giancarlo Paoletti, Enzo Ruggeri, Laura Iezzi, Isabella Sperduti, Lucia Mentuccia, Agnese Fabbri, Marcello Maugeri-Saccà, Luca Moscetti, Maddalena Barba, Patrizia Vici
To characterize determinants of treatment outcome in a real world population of 161 post-menopausal hormone receptor-positive metastatic breast cancer patients treated with fulvestrant. Descriptive statistics for demographics, anthropometrics, clinical and molecular characteristic were compared across subgroups of sensitivity/resistance to prior endocrine therapy and tested in uni/multivariate models. Clinical benefit was more common in sensitive patients with higher estrogen receptor expression and when fulvestrant was given in first line (p=0...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968163/monarch-3-abemaciclib-as-initial-therapy-for-advanced-breast-cancer
#13
RANDOMIZED CONTROLLED TRIAL
Matthew P Goetz, Masakazu Toi, Mario Campone, Joohyuk Sohn, Shani Paluch-Shimon, Jens Huober, In Hae Park, Olivier Trédan, Shin-Cheh Chen, Luis Manso, Orit C Freedman, Georgina Garnica Jaliffe, Tammy Forrester, Martin Frenzel, Susana Barriga, Ian C Smith, Nawel Bourayou, Angelo Di Leo
Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting...
November 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28961554/cdk4-6-inhibition-in-early-and-metastatic-breast-cancer-a-review
#14
REVIEW
A F de Groot, C J Kuijpers, J R Kroep
Breast cancer (BC) is responsible for 14% of cancer-related deaths in women [1]. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of selective drugs, offering an effective and tolerable treatment. CDK4/6 inhibitors induce cell cycle arrest in the G1 phase, and may thereby prevent tumour progression. Three CDK4/6 inhibitors have been tested in clinical BC trials: palbociclib, ribociclib, and abemaciclib. The Food and Drug Administration (FDA) and European Commission (EMA) have approved palbociclib for the treatment of patients HR+ HER2- locally advanced or metastatic BC (aBC) in combination with an aromatase inhibitor as initial therapy in postmenopausal women or in combination with fulvestrant in women who have received prior endocrine therapy...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28937965/artemin-promotes-oncogenicity-metastasis-and-drug-resistance-in-cancer-cells
#15
Kamal Hezam, Jiahao Jiang, Fumou Sun, Xinrong Zhang, Juan Zhang
Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro...
September 22, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28915603/estrogen-promotes-tumor-metastasis-via-estrogen-receptor-beta-mediated-regulation-of-matrix-metalloproteinase-2-in-non-small-cell-lung-cancer
#16
Sheng Fan, Yongde Liao, Changyu Liu, Quanfu Huang, Huifang Liang, Bo Ai, Shegnling Fu, Sheng Zhou
In non-small cell lung cancer (NSCLC), estrogen significantly promotes NSCLC cell growth via estrogen receptor beta (ERβ). However, the effects by which ERβ contributes to metastasis in NSCLC have not been previously reported. This study aims at defining whether the stimulation of ERβ promotes NSCLC metastasis in vitro and in vivo. Here, Our results showed that estrogen and ERβ agonist enhanced aggressiveness of two lung cancer cell lines (A549 and H1793) and promoted murine lung metastasis formation. ER-inhibitor Fulvestrant treatment or ERβ-knockdown significantly suppressed the migration, invasion and nodule formation of NSCLC cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903361/fulvestrant-500-milligrams-as-endocrine-therapy-for-endocrine-sensitive-advanced-breast-cancer-patients-in-the-real-world-the-ful500-prospective-observational-trial
#17
Luca Moscetti, Maria Agnese Fabbri, Clara Natoli, Patrizia Vici, Teresa Gamucci, Isabella Sperduti, Laura Iezzi, Elena Iattoni, Laura Pizzuti, Carmine Roma, Angela Vaccaro, Giuliana D'Auria, Mariella Mauri, Lucia Mentuccia, Antonino Grassadonia, Maddalena Barba, Enzo Maria Ruggeri
The observational prospective trial herein presented aimed at evaluating the efficacy of fulvestrant 500 mg in the treatment of endocrine sensitive advanced breast cancer patients from the real world setting. The primary end point was clinical benefit rate (CBR). Secondary end points were overall survival (OS), progression free survival (PFS) and tolerability. One hundred sixty three patients were enrolled. At a median follow up of 20 months, the 61% of patients reached CBR, whose median duration was 10.8 months...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893547/17%C3%AE-estradiol-modulates-cell-proliferation-of-medullary-cords-during-ovarian-differentiation-of-the-lepidochelys-olivacea-sea-turtle
#18
Verónica Díaz-Hernández, Alma Vázquez-Gómez, Alejandro Marmolejo-Valencia, Luis Manuel Montaño, Horacio Merchant-Larios
In turtles undergoing temperature sex determination (TSD), bipotential gonads express Sox9 in medullary cords at both female- (FPT) and male-producing temperatures (MPT). Subsequently, when the sex fate of medullary cords becomes dimorphic, at FPT, Sox9 is downregulated, whereas at MPT, its expression is maintained. Medullary cords in the ovary turn into ovarian lacuna, whereas in the testis they differentiate as seminiferous cords. When embryos of Lepidochelys olivacea sea turtle are incubated at MPT and treated with estradiol, Sox9 expression persists in the medullary cords in the form of tiny ovotestis-like formations...
November 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28885430/aggressive-angiomyxoma-of-the-vulva-and-bladder
#19
Mihae Song, Michelle Glasgow, Paari Murugan, Colleen Rivard
BACKGROUND: Aggressive angiomyxoma is a rare, locally infiltrative tumor, frequently occurring in female patients. Although wide local excision is considered standard therapy, radical surgery may be needed. CASE: A 49-year-old woman presented with an aggressive angiomyxoma involving the vulva and bladder. Given the hormone receptor status and size of the tumor, the patient was initially treated with fulvestrant and goserelin acetate in an attempt to reduce the size of the mass...
October 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28882815/childhood-tolerance-of-severe-influenza-a-mortality-analysis-in-mice
#20
Freeman Suber, Lester Kobzik
During the 1918 influenza pandemic, children experienced substantially lower mortality than adults, a striking but unexplained finding. Whether this was due to enhanced resistance (reduced virus load) or better tolerance (reduced impact of infection) has not been defined. We found that prepubertal mice infected with H1N1 influenza virus also showed greater survival than infected pubertal mice, despite similar virus loads. Transcriptome profiling of infected lungs identified estrogen as a regulator of susceptibility in both sexes, and also linked better survival to late expression of IL-1beta...
September 7, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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