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https://www.readbyqxmd.com/read/28102330/new-insights-into-fetal-mammary-gland-morphogenesis-differential-effects-of-natural-and-environmental-estrogens
#1
Lucia Speroni, Maria Voutilainen, Marja L Mikkola, Skylar A Klager, Cheryl M Schaeberle, Carlos Sonnenschein, Ana M Soto
An increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen's direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E)14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088469/estrogen-induced-expression-of-tissue-factor-pathway-inhibitor-2-in-mcf7-cells-involves-lysine-specific-demethylase-1
#2
Marianne S Andresen, Huda Omar Ali, Christiane Filion Myklebust, Per Morten Sandset, Benedicte Stavik, Nina Iversen, Grethe Skretting
Hormone-sensitive cancers can be influenced by estrogens, a process usually mediated through the estrogen receptor (ER). Tissue factor pathway inhibitor type 2 (TFPI-2) is a Kunitz-type serine protease inhibitor involved in regulating the extracellular matrix. The present study demonstrates that the expression of TFPI-2 can be induced by estrogens. Breast cancer data from GOBO displayed increased levels of TFPI-2 and increased survival in patients with ERα+ tumors. Treatment of MCF7 cells (ERα+) with 17β-estradiol (E2) or 17α-ethinyl estradiol (EE2) increased TFPI-2 mRNA and protein levels...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28074314/a-novel-effect-of-%C3%AE-adrenergic-receptor-on-mammary-branching-morphogenesis-and-its-possible-implications-in-breast-cancer
#3
Lucía Gargiulo, María May, Ezequiel M Rivero, Sabrina Copsel, Caroline Lamb, John Lydon, Carlos Davio, Claudia Lanari, Isabel A Lüthy, Ariana Bruzzone
Understanding the mechanisms that govern normal mammary gland development is crucial to the comprehension of breast cancer etiology. β-adrenergic receptors (β-AR) are targets of endogenous catecholamines such as epinephrine that have gained importance in the context of cancer biology. Differences in β2-AR expression levels may be responsible for the effects of epinephrine on tumor vs non-tumorigenic breast cell lines, the latter expressing higher levels of β2-AR. To study regulation of the breast cell phenotype by β2-AR, we over-expressed β2-AR in MCF-7 breast cancer cells and knocked-down the receptor in non-tumorigenic MCF-10A breast cells...
January 11, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28073843/active-estrogen-receptor-alpha-signaling-in-ovarian-cancer-models-and-clinical-specimens
#4
Courtney L Andersen, Matthew J Sikora, Michelle M Boisen, Tianzhou Ma, Alec Christie, George Tseng, Yong Seok Park, Soumya Luthra, Uma Chandran, Paul Haluska, Gina Mantia-Smaldone, Kunle Odunsi, Karen McLean, Adrian V Lee, Esther Elishaev, Robert P Edwards, Steffi Oesterreich
PURPOSE: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, estrogen receptor-alpha has been understudied as a target in this disease. We sought to identify hormone-responsive, estrogen receptor-alpha-dependent HGSOC. EXPERIMENTAL DESIGN: We characterized endocrine response in HGSOC cells across culture conditions (2-D, 3-D, forced suspension) and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28045951/an-experimental-analysis-of-the-molecular-effects-of-trastuzumab-herceptin-and-fulvestrant-falsodex-as-single-agents-or-in-combination-on-human-hr-her2-breast-cancer-cell-lines-and-mouse-tumor-xenografts
#5
Qing Chen, Ziyi Weng, Yunshu Lu, Yijun Jia, Longlong Ding, Fang Bai, Meixin Ge, Qing Lin, Kejin Wu
PURPOSE: To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS: Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28043824/esr1-and-its-antagonist-fulvestrant-in-pituitary-adenomas
#6
Hua Gao, Yake Xue, Lei Cao, Qian Liu, Chunhui Liu, Xiaosong Shan, Hongyun Wang, Yi Gu, Yazhuo Zhang
Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups...
December 31, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28043088/fulvestrant-for-hormone-sensitive-metastatic-breast-cancer
#7
REVIEW
Clara I Lee, Annabel Goodwin, Nicholas Wilcken
BACKGROUND: Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for women with hormone-sensitive advanced breast cancer. The goal of such systemic therapy in this setting is to reduce symptoms, improve quality of life, and increase survival time. OBJECTIVES: To assess the efficacy and safety of fulvestrant for hormone-sensitive locally advanced or metastatic breast cancer in postmenopausal women, as compared to other standard endocrine agents...
January 3, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28011460/18f-fluoroestradiol-pet-ct-measurement-of-estrogen-receptor-suppression-during-a-phase-i-trial-of-the-novel-estrogen-receptor-targeted-therapeutic-gdc-0810
#8
Yingbing Wang, Karen Ayres, Debra A Goldman, Maura N Dickler, Aditya Bardia, Ingrid A Mayer, Eric P Winer, Jill Fredrickson, Carlos L Arteaga, José Baselga, H Charles Manning, Umar Mahmood, Gary A Ulaner
PURPOSE: Evaluate 18F-fluoroestradiol (FES) PET/CT as a biomarker of estrogen receptor (ER) occupancy and/or downregulation during phase I dose escalation of the novel ER targeting therapeutic GDC-0810, and help select drug dosage for subsequent clinical trials. EXPERIMENTAL DESIGN: In a phase I clinical trial of GDC-0810, patients with ER-positive metastatic breast cancer underwent FES PET/CT before beginning therapy and at cycle 2, day 3 of GDC-0810 therapy. Up to five target lesions were selected per patient, and FES SUV corrected for background was recorded for each lesion pre-therapy and on-therapy...
December 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28011074/patient-database-analysis-of-fulvestrant-500%C3%A2-mg-in-the-treatment-of-metastatic-breast-cancer-a-european-perspective
#9
Paolo Marchetti, Nicolai Maass, Joseph Gligorov, Karin Berger, Finlay MacDougall, Jukka Montonen, Jan Lewis
INTRODUCTION: Clinical guidelines recommend that patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) should be preferentially treated with endocrine therapy. Fulvestrant (a selective estrogen receptor degrader) is approved for use in these patients following relapse after, or relapse or progression during, antiestrogen therapy. This descriptive study analyzed European treatment patterns for HR-positive MBC in real-world clinical practice. METHODS: The IMS Oncology Analyzer (OA), a retrospective cancer treatment database reporting physician-entered patient case histories, was used to identify records for postmenopausal women with HR-positive MBC from April 1, 2004 to June 30, 2013 in France, Germany, Italy, and Spain...
December 20, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28007942/everolimus-boosts-endocrine-therapy-for-breast-cancer
#10
(no author information available yet)
In a phase II trial, the mTOR inhibitor everolimus, combined with the endocrine therapy fulvestrant, improved progression-free survival in postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer who had become resistant to aromatase inhibitors.
December 22, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28000875/fulvestrant-reverses-doxorubicin-resistance-in-multidrug-resistant-breast-cell-lines-independent-of-estrogen-receptor-expression
#11
Yuan Huang, Donghai Jiang, Meihua Sui, Xiaojia Wang, Weimin Fan
Drug resistance, a major obstacle to successful cancer chemotherapy, frequently occurs in recurrent or metastatic breast cancer and results in poor clinical response. Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer. In this study, we evaluated the combination treatment of fulvestrant and doxorubicin in ER-negative multidrug-resistant (MDR) breast cancer cell lines Bads‑200 and Bats‑72. Fulvestrant potentiated doxorubicin-induced cytotoxicity, apoptosis and G2/M arrest with upregulation of cyclin B1...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27986707/activating-esr1-mutations-differentially-impact-the-efficacy-of-er-antagonists
#12
Weiyi Toy, Hazel Weir, Pedram Razavi, Mandy Lawson, Anne U Goeppert, Anne Marie Mazzola, Aaron Smith, Joanne Wilson, Christopher Morrow, Wai Lin Wong, Elisa De Stanchina, Kathryn E Carlson, Teresa S Martin, Sharmeen Uddin, Zhiqiang Li, Sean Fanning, John A Katzenellenbogen, Geoffrey Greene, José Baselga, Sarat Chandarlapaty
Recent studies have identified somatic ESR1 mutations in patients with metastatic breast cancer (MBC) and found some of them to promote estrogen-independent activation of the receptor. The degree to which all recurrent mutants can drive estrogen-independent activities and reduced sensitivity to ER antagonists like fulvestrant is not established. In this report, we characterize the spectrum of ESR1 mutations from over 900 patients. ESR1 mutations were detected in 10%, with D538G being the most frequent (36%), followed by Y537S (14%)...
December 16, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27967255/endocrine-therapy-in-epithelial-ovarian-cancer
#13
Simon P Langdon, Charlie Gourley, Hani Gabra, Barbara Stanley
The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers...
December 24, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27923036/cotargeting-of-cyp-19-aromatase-and-emerging-pivotal-signalling-pathways-in-metastatic-breast-cancer
#14
REVIEW
Stine Daldorff, Randi Margit Ruud Mathiesen, Olav Erich Yri, Hilde Presterud Ødegård, Jürgen Geisler
Aromatase inhibition is one of the cornerstones of modern endocrine therapy of oestrogen receptor-positive (ER+) metastatic breast cancer (MBC). The nonsteroidal aromatase inhibitors anastrozole and letrozole, as well as the steroidal aromatase inactivator exemestane, are the preferred drugs and established worldwide in all clinical phases of the disease. However, although many patients suffering from MBC experience an initial stabilisation of their metastatic burden, drug resistance and disease progression occur frequently, following in general only a few months on treatment...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27908454/fulvestrant-500-mg-versus-anastrozole-1-mg-for-hormone-receptor-positive-advanced-breast-cancer-falcon-an-international-randomised-double-blind-phase-3-trial
#15
John F R Robertson, Igor M Bondarenko, Ekaterina Trishkina, Mikhail Dvorkin, Lawrence Panasci, Alexey Manikhas, Yaroslav Shparyk, Servando Cardona-Huerta, Kwok-Leung Cheung, Manuel Jesus Philco-Salas, Manuel Ruiz-Borrego, Zhimin Shao, Shinzaburo Noguchi, Jacqui Rowbottom, Mary Stuart, Lynda M Grinsted, Mehdi Fazal, Matthew J Ellis
BACKGROUND: Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy. METHODS: In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confirmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries...
December 17, 2017: Lancet
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#16
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27895744/identification-of-targets-of-mirna-221-and-mirna-222-in-fulvestrant-resistant-breast-cancer
#17
Pengfei Liu, Manna Sun, Wenhua Jiang, Jinkun Zhao, Chunyong Liang, Huilai Zhang
The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895513/tumor-suppressor-ing4-inhibits-estrogen-receptor-activity-in-breast-cancer-cells
#18
Madeline M Keenen, Suwon Kim
Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose-response of estrogen...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27888136/different-epigenetic-mechanisms-of-er%C3%AE-implicated-in-the-fate-of-fulvestrant-resistant-breast-cancer
#19
Kouki Tsuboi, Yosuke Kaneko, Takamasa Nagatomo, Rika Fujii, Toru Hanamura, Tatsuyuki Gohno, Yuri Yamaguchi, Toshifumi Niwa, Shin-Ichi Hayashi
Approximately 70% of breast cancers express estrogen receptor α (ERα), which plays critical roles in breast cancer development. Fulvestrant has been effectively used to treat ERα-positive breast cancer, although resistance remains a critical problem. To elucidate the mechanism of resistance to fulvestrant, we established fulvestrant-resistant cell-lines named MFR (MCF-7 derived fulvestrant resistance) and TFR (T-47D derived fulvestrant resistance) from the ERα-positive luminal breast cancer cell lines MCF-7 and T-47D, respectively...
November 22, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27885811/17-%C3%AE-estradiol-inhibits-hepatitis-c-virus-mainly-by-interference-with-the-release-phase-of-its-life-cycle
#20
Andrea Magri, Matteo N Barbaglia, Chiara Z Foglia, Elisa Boccato, Michela E Burlone, Sarah Cole, Paola Giarda, Elena Grossini, Arvind H Patel, Rosalba Minisini, Mario Pirisi
BACKGROUND & AIMS: Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values...
November 7, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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