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https://www.readbyqxmd.com/read/28775043/oestrogen-inhibition-reverses-pulmonary-arterial-hypertension-and-associated-metabolic-defects
#1
Xinping Chen, Eric D Austin, Megha Talati, Joshua P Fessel, Eric H Farber-Eger, Evan L Brittain, Anna R Hemnes, James E Loyd, James West
Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice.The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28770167/fatal-statin-induced-rhabdomyolysis-by-possible-interaction-with-palbociclib
#2
Kellie Lynn Nelson, David Stenehjem, Meghan Driscoll, Glynn Weldon Gilcrease
A 60- to 65-year-old female on prior statin therapy was initiated on palbociclib and fulvestrant for the treatment of metastatic, hormone-receptor positive breast cancer. She subsequently developed sudden progressive muscle weakness that progressed to death within weeks. The patient noticed progressive proximal muscle weakness after two cycles of palbociclib, with no other medication changes in the interim. This rapidly progressed and resulted in death within 7 days of presentation to hospital. There has been one previous report of rhabdmyolysis with palbociclib, occurring in a patient on concomitant statin...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28763032/a-chip-for-estrogen-receptor-action-detection-of-biomarkers-released-by-mcf-7-cells-through-estrogenic-and-anti-estrogenic-effects
#3
Konstanze Gier, Claudia Preininger, Ursula Sauer
The fluorescence-based multi-analyte chip platform for the analysis of estrogenic and anti-estrogenic substances is a new in vitro tool for the high throughput screening of environmental samples. In contrast to existing tools, the chip investigates the complex action of xenoestrogens in a human cell model by characterizing protein expression. It allows for the quantification of 10 proteins secreted by MCF-7 cells, representing various biological and pathological endpoints of endocrine action and distinguishing between estrogen- and anti-estrogen-dependent secretion of proteins...
August 1, 2017: Sensors
https://www.readbyqxmd.com/read/28760601/a-functional-drug-re-purposing-screening-identifies-carfilzomib-as-a-drug-preventing-17%C3%AE-estradiol-er%C3%AE-signaling-and-cell-proliferation-in-breast-cancer-cells
#4
Claudia Busonero, Stefano Leone, Cinzia Klemm, Filippo Acconcia
Most cases of breast cancer (BC) are estrogen receptor α-positive (ERα+) at diagnosis. The presence of ERα drives the therapeutic approach for this disease, which often consists of endocrine therapy (ET). 4OH-Tamoxifen and faslodex (i.e., fulvestrant - ICI182,780) are two ETs that render tumor cells insensitive to 17β-estradiol (E2)-dependent proliferative stimuli and prevent BC progression. However, ET has limitations and serious failures in different tissues and organs. Thus, there is an urgent need to identify novel drugs to fight BC in the clinic...
July 29, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28752187/systematic-review-and-network-meta-analysis-comparing-palbociclib-with-chemotherapy-agents-for-the-treatment-of-postmenopausal-women-with-hr-positive-and-her2-negative-advanced-metastatic-breast-cancer
#5
Florence R Wilson, Abhishek Varu, Debanjali Mitra, Chris Cameron, Shrividya Iyer
PURPOSE: To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line). METHODS: A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC...
July 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28751448/association-of-fgfr1-with-er%C3%AE-maintains-ligand-independent-er-transcription-and-mediates-resistance-to-estrogen-deprivation-in-er-breast-cancer
#6
Luigi Formisano, Kimberly Mae Stauffer, Christian D Young, Neil E Bhola, Angel L Guerrero-Zotano, Valerie M Jansen, Monica M Estrada, Katherine E Hutchinson, Jennifer M Giltnane, Luis J Schwarz, Yao Lu, Justin M Balko, Olivier Deas, Stefano Cairo, Jean-Gabriel Judde, Ingrid A Mayer, Melinda Sanders, Teresa C Dugger, Roberto Bianco, Thomas Stricker, Carlos L Arteaga
FGFR1 amplification occurs in ~15% of ER+ human breast cancers. We investigated mechanisms by which FGFR1 amplification confers antiestrogen resistance to ER+ breast cancer.<br /><br />Experimental Design: ER+ tumors from patients treated with letrozole before surgery were subjected to Ki67 immunohistochemistry, FGFR1 FISH, and RNA-sequencing. ER+/FGFR1 amplified breast cancer cells and patient-derived xenografts (PDXs) were treated with FGFR1 siRNA or the FGFR tyrosine kinase inhibitor lucitanib...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28747642/a-preliminary-study-of-18-f-fes-pet-ct-in-predicting-metastatic-breast-cancer-in-patients-receiving-docetaxel-or-fulvestrant-with-docetaxel
#7
Chengcheng Gong, Zhongyi Yang, Yifei Sun, Jian Zhang, Chunlei Zheng, Leiping Wang, Yongping Zhang, Jing Xue, Zhifeng Yao, Herong Pan, Biyun Wang, Yingjian Zhang
The present explorative study was initiated to evaluate the clinical value of (18)F-FES PET/CT in monitoring the change of estrogen receptor (ER) expression and potential predictive value in metastatic breast cancer patients. Twenty-two pathology-confirmed breast cancer patients were prospectively enrolled and randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel + fulvestrant, n = 8). The percentage of patients without disease progression after 12 months (PFS > 12 months) was 62...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28725277/sabcs-2016-systemic-therapy-for-metastatic-breast-cancer
#8
REVIEW
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Richard Greil
At the 2016 San Antonio Breast Cancer Symposium, several interesting phase II and phase III studies investigating systemic therapies for metastatic breast cancer were presented. The PrEGOC 0102 trial demonstrated that the combination of fulvestrant plus everolimus is safe and effective and could be an alternative to exemestane plus everolimus for selected patients with hormone-receptor positive, HER2-negative disease. The pan-PI3K inhibitor buparlisib showed some activity in combination with fulvestrant after failure of everolimus in the BELLE-3 trial...
2017: Memo
https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#9
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28719836/long-term-management-of-patients-with-hormone-receptor-positive-metastatic-breast-cancer-concepts-for-sequential-and-combination-endocrine-based-therapies
#10
REVIEW
Adam M Brufsky
Treatment options for hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) continue to increase in parallel with expanding knowledge about the complex biology of breast cancer subtypes and resistance mechanisms to endocrine therapy. For patients with HR-positive MBC, there are now an unprecedented number of endocrine-based treatment options that can improve long-term outcomes, while preserving or optimizing quality of life, and that can be used before selecting more cytotoxic chemotherapeutic regimens...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28717399/fulvestrant-in-advanced-breast-cancer-evidence-to-date-and-place-in-therapy
#11
REVIEW
Katalin Boér
Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28711793/efficacy-and-safety-of-everolimus-and-exemestane-in-hormone-receptor-positive-hr-human-epidermal-growth-factor-negative-her2-advanced-breast-cancer-patients-new-insights-beyond-clinical-trials-the-eva-study
#12
M E Cazzaniga, M Airoldi, V Arcangeli, S Artale, F Atzori, A Ballerio, G V Bianchi, L Blasi, S Campidoglio, M Ciccarese, M C Cursano, M Piezzo, A Fabi, L Ferrari, A Ferzi, C Ficorella, A Frassoldati, A Fumagalli, O Garrone, V Gebbia, D Generali, N La Verde, M Maur, A Michelotti, G Moretti, A Musolino, R Palumbo, M Pistelli, M Porpiglia, D Sartori, C Scavelli, A Schirone, A Turletti, M R Valerio, P Vici, A Zambelli, L Clivio, V Torri
BACKGROUND: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant...
July 13, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28701262/effects-of-low-dose-bisphenol-a-on-calcium-ion-influx-and-on-genes-of-proliferation-and-differentiation-in-immortalized-human-gingival-cells-in-vitro-the-role-of-estrogen-receptor-beta
#13
Matthias Ehrenmann, Pascal Tomakidi, Elmar Hellwig, Simon Daniel Schulz, Olga Polydorou
OBJECTIVES: Relating to low-dose Bisphenol-A (BPA), there is still a lack of mechanistic studies in oral cells, representing the first targets of BPA by oral intake. The objective of this study was to investigate an assumed mechanistic interrelationship between both low-dose BPA-modulated Calcium ion (Ca(2+)) influx and cell behavior, and the estrogen receptor β (ERβ), in oral mucosal cells. METHODS: Indirect immunofluorescence (IIF) was conducted on estrogen receptor beta (ERβ) activity after 1, 3, and 6days in response to 39nM BPA, 15μM BPA, and 200 pM 17β-Estradiol (E2)...
July 9, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28683005/the-use-of-endometrial-cancer-patient-derived-organoid-culture-for-drug-sensitivity-testing-is-feasible
#14
Eugenia Girda, Eric C Huang, Gary S Leiserowitz, Lloyd H Smith
OBJECTIVE: Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer. METHODS: Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium...
July 5, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28680952/a-review-of-fulvestrant-in-breast-cancer
#15
REVIEW
Mark R Nathan, Peter Schmid
Fulvestrant is a selective estrogen receptor degrader that binds, blocks and degrades the estrogen receptor (ER), leading to complete inhibition of estrogen signaling through the ER. This review article further explains the mechanism of action of the drug and goes on to review the trials carried out to optimize its dosing. Multiple trials have been undertaken to compare fulvestrant with other endocrine treatments, and results have shown it to have similar efficacy to anastrozole, tamoxifen and exemestane at 250 mg every 28 days...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28675545/cost-effectiveness-analysis-of-fulvestrant-versus-anastrozole-as-first-line-treatment-for-hormone-receptor-positive-advanced-breast-cancer
#16
H Ding, L Fang, W Xin, Y Tong, Q Zhou, P Huang
Although recent studies demonstrated that fulvestrant is superior to anastrozole as first-line treatment for hormone receptor (HR)-positive advanced breast cancer, the cost-effectiveness of fulvestrant versus anastrozole remained uncertain. Thus, the current study aimed to evaluate the cost-effectiveness of fulvestrant compared with anastrozole in the first-line setting. A Markov model consisting of three health states (stable, progressive and dead) was constructed to simulate a hypothetical cohort of patients with HR-positive advanced breast cancer...
July 3, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28669712/lessons-in-precision-oncology-from-neoadjuvant-endocrine-therapy-trials-in-er-breast-cancer
#17
Matthew J Ellis
For post-menopausal women with clinical stage II/III estrogen receptor positive (ER+) breast cancer neoadjuvant endocrine therapy (NET) is an under-utilized and low-toxicity alternative to chemotherapy for increasing breast conservation rates. Individual responses to endocrine therapy can also be used to tailor systemic treatment. The Preoperative Endocrine Prognostic Index (PEPI) was developed to identify patients at low risk of relapse after NET so that adjuvant chemotherapy can safely be avoided. In a recent validation study, patients with pathological stage 1 or 2A breast cancers with a Ki67 value of 2...
June 29, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28665682/the-role-of-neratinib-in-her2-driven-breast-cancer
#18
Mathew A Cherian, Cynthia X Ma
Up to 25% of patients with early-stage HER2+ breast cancer relapse despite adjuvant trastuzumab-based regimens and virtually all patients with metastatic disease eventually die from resistance to existing treatment options. In addition, recent studies indicate that activating HER2 mutations without gene amplification could drive tumor growth in a subset of HER2-ve breast cancer that is not currently eligible for HER2-targeted agents. Neratinib is an irreversible HER kinase inhibitor with activity as extended adjuvant therapy following standard trastuzumab-based adjuvant treatment in a Phase III trial...
June 30, 2017: Future Oncology
https://www.readbyqxmd.com/read/28657360/a-current-and-comprehensive-review-of-cyclin-dependent-kinase-inhibitors-for-the-treatment-of-metastatic-breast-cancer
#19
Burak Bilgin, Mehmet A N Sendur, Didem Şener Dede, Muhammed Bülent Akıncı, Bülent Yalçın
BACKGROUND: Resistance to endocrine treatment generally occurs over time, especially in the metastatic stage. In this paper, we aimed to review the mechanisms of cyclin-dependent kinase (CDK) 4/6 inhibition and clinical usage of new agents in the light of recent literature updates. SCOPE: A literature search was carried out using PubMed, Medline and ASCO and ESMO annual-meeting abstracts by using the following search keywords; "palbociclib", "abemaciclib", "ribociclib", "cyclin-dependent kinase inhibitors" and "CDK 4/6" in metastatic breast cancer (MBC)...
July 25, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28657320/adamantyl-antiestrogens-with-novel-side-chains-reveal-a-spectrum-of-activities-in-suppressing-estrogen-receptor-mediated-activities-in-breast-cancer-cells
#20
Jian Min, Valeria Sanabria Guillen, Abhishek Sharma, Yuechao Zhao, Yvonne Ziegler, Ping Gong, Christopher G Mayne, Sathish Srinivasan, Sung Hoon Kim, Kathryn E Carlson, Kendall W Nettles, Benita S Katzenellenbogen, John A Katzenellenbogen
To search for new antiestrogens more effective in treating breast cancers, we explored alternatives to the acrylic acid side chain used in many antiestrogens. To facilitate our search, we used a simple adamantyl ligand core that by avoiding stereochemical issues enabled rapid synthesis of acrylate ketone, ester, and amide analogs. All compounds were high affinity estrogen receptor α (ERα) ligands but displayed a range of efficacies and potencies as antiproliferative and ERα-downregulating agents. There were large differences in activity between compounds having minor structural changes, but antiproliferative and ERα-downregulating efficacies generally paralleled one another...
July 27, 2017: Journal of Medicinal Chemistry
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