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https://www.readbyqxmd.com/read/28324269/metformin-sensitizes-triple-negative-breast-cancer-to-proapoptotic-trail-receptor-agonists-by-suppressing-xiap-expression
#1
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
PURPOSE: Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. METHODS: Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28324268/a-phase-ii-study-of-combined-ridaforolimus-and-dalotuzumab-compared-with-exemestane-in-patients-with-estrogen-receptor-positive-breast-cancer
#2
José Baselga, Serafin M Morales, Ahmad Awada, Joanne L Blum, Antoinette R Tan, Marianne Ewertz, Javier Cortes, Beverly Moy, Kathryn J Ruddy, Tufia Haddad, Eva M Ciruelos, Peter Vuylsteke, Scot Ebbinghaus, Ellie Im, Lamar Eaton, Kumudu Pathiraja, Christine Gause, David Mauro, Mary Beth Jones, Hope S Rugo
PURPOSE: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). METHODS: This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857)...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28324066/hippocampal-aromatization-modulates-spatial-memory-and-characteristics-of-the-synaptic-membrane-in-the-male-zebra-finch
#3
David J Bailey, Yekaterina V Makeyeva, Elizabeth R Paitel, Alyssa L Pedersen, Angel T Hon, Jordan A Gunderson, Colin J Saldanha
The estrogen-synthesizing enzyme aromatase is abundant at the synapse in the zebra finch hippocampus (HP) and its inhibition impairs spatial memory function. To more fully test the role of local estradiol (E2) synthesis in memory, the HP of adult male zebra finches was exposed to either control pellets or those containing the aromatase inhibitor ATD, ATD and E2, ATD and the G protein-coupled estrogen receptor (GPER) agonist G1, or the antagonist G15 alone. Birds were tested for spatial memory acquisition and performance, and HP levels of the postsynaptic protein PSD95 were measured...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324061/progesterone-protects-against-bpa-induced-arrhythmias-in-female-rat-cardiac-myocytes-via-rapid-signaling
#4
Jianyong Ma, Kui Hong, Hong-Sheng Wang
Bisphenol A (BPA) is an estrogenic endocrine disrupting chemical (EDC) that has a range of potential adverse health effects. Previously we showed that acute exposure to BPA promoted arrhythmias in female rat hearts through estrogen receptor rapid signaling. Progesterone (P4) and estrogen have antagonistic or complementary actions in a number of tissues and systems. In the current study, we examined the influence, and possible protective effect, of P4 on the rapid cardiac actions of BPA in female rat cardiac myocytes...
January 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324026/gonadotropin-inhibitory-hormone-gnih-the-piscine-ortholog-of-lpxrfa-participates-in-17%C3%AE-estradiol-feedback-in-female-goldfish-reproduction
#5
Xin Qi, Wenyi Zhou, Qingqing Wang, Liang Guo, Danqi Lu, Haoran Lin
Gonadotropin-inhibitory hormone (GnIH) plays a critical role in regulating GnRH, GtH and steroidogenesis in teleosts. In the present study, we sought to determine whether E2 (17β-estradiol) acts directly on GnIH neurons to regulate reproduction in goldfish, a seasonal breeder, and we investigated the role of estrogen receptors in mediating this process. We found that GnIH neurons co-express three types of ERs. Ovariectomy and letrozole implantation into female goldfish at the vitellogenic stage elicited a significant decrease in the expression of GnIH mRNA, and E2 supplementation abolished this effect...
January 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323982/versican-proteolysis-by-adamts-proteases-and-its-influence-on-sex-steroid-receptor-expression-in-uterine-leiomyoma
#6
Ndeye-Aicha Gueye, Timothy J Mead, Christopher D Koch, Charles V Biscotti, Tommaso Falcone, Suneel S Apte
Context: Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. Objective: To investigate ADAMTS protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. Design: We used qRT-PCR, western blotting, immunohistochemistry and RNA in situ hybridization for analysis of myometrium, leiomyoma, and immortalized myometrium and leiomyoma cells...
February 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323976/protective-effects-of-fetal-zone-steroids-are-comparable-to-estradiol-in-hyperoxia-induced-cell-death-of-immature-glia
#7
Stephanie Hübner, Donna E Sunny, Christine Pöhlke, Johanna Ruhnau, Antje Vogelgesang, Bettina Reich, Matthias Heckmann
Impaired neurodevelopment in preterm infants is caused by prematurity itself; however, hypoxia/ischemia, inflammation, and hyperoxia contribute to the extent of impairment. Because preterm birth is accompanied by a dramatic decrease in 17β-estradiol (E2) and progesterone, preliminary clinical studies have been carried out to substitute these steroids in preterm infants; however, they failed to confirm significantly improved neurological outcomes. We therefore hypothesized that the persistently high postnatal production of fetal zone steroids (mainly dehydroepiandrosterone (DHEA)) until term could interfere with E2-mediated protection...
March 3, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323936/the-steroid-metabolome-in-the-isolated-ovarian-follicle-and-its-response-to-androgen-exposure-and-antagonism
#8
Marie Lebbe, Angela E Taylor, Jenny A Visser, Jackson Kirkman-Brown, Teresa K Woodruff, Wiebke Arlt
The ovarian follicle is a major site of steroidogenesis, crucially required for normal ovarian function and female reproduction. Our understanding of androgen synthesis and metabolism in the developing follicle has been limited by sensitivity and specificity issues of previously used assays. Here we used liquid chromatography-tandem mass spectrometry to map the stage-dependent endogenous steroid metabolome in an encapsulated in vitro follicle growth system, from murine secondary through antral follicles. Furthermore, follicles were cultured in the presence of androgen precursors, non-aromatizable active androgen and androgen receptor (AR) antagonist to assess effects on steroidogenesis and follicle development...
February 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323912/sex-hormones-and-cardiometabolic-health-role-of-estrogen-and-estrogen-receptors
#9
Deborah Clegg, Andrea L Hevener, Kerrie L Moreau, Eugenia Morselli, Alfredo Criollo, Rachael E Van Pelt, Victoria J Vieira-Potter
With increased life expectancy, women will spend over three decades of life post-menopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320163/inhibition-of-17-beta-estradiol-on-neuronal-excitability-via-enhancing-girk1-mediated-inwardly-rectifying-potassium-currents-and-girk1-expression
#10
Yuwen Zhang, Yian Huang, Guoxiang Wang, Xin Wang, Yun Wang
BACKGROUND: Catamenial epilepsy is a common central nervous system disease in female, which is influenced by the 17-β-estradiol (estrogen) level during the menstrual cycle. Low level (<0.05ng/ml) of estrogen normally accompanies with the perimenstrual classification of catamenial epilepsy, however, without clear mechanism. In previous studies, estrogen has been demonstrated to possess widely regulatory effects on potassium channels. Here, the effect of 17-β-estradiol on modulating inwardly rectifying K(+) (Kir) currents was investigated in cultured hippocampal neurons...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319747/integration-of-in-silico-methods-and-computational-systems-biology-to-explore-endocrine-disrupting-chemical-binding-with-nuclear-hormone-receptors
#11
P Ruiz, A Sack, M Wampole, S Bobst, M Vracko
Thousands of potential endocrine-disrupting chemicals present difficult regulatory challenges. Endocrine-disrupting chemicals can interfere with several nuclear hormone receptors associated with a variety of adverse health effects. The U.S. Environmental Protection Agency (U.S. EPA) has released its reviews of Tier 1 screening assay results for a set of pesticides in the Endocrine Disruptor Screening Program (EDSP), and recently, the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) data...
March 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28319725/antiestrogen-use-in-breast-cancer-patients-reduces-the-risk-of-subsequent-lung-cancer-a-population-based-study
#12
Sung-Chao Chu, Chia-Jung Hsieh, Tso-Fu Wang, Mun-Kun Hong, Tang-Yuan Chu
BACKGROUND: There is accumulating epidemiological and preclinical evidence that estrogen might be a driver of lung cancer. Breast cancer survivors can offer a unique patient cohort to examine the effect of antiestrogen therapy on lung cancer carcinogenesis because many of these women would have received long-term selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) as adjuvant treatment. Our hypothesis is that estrogens play a role in lung cancer development, and that antiestrogen therapy would affect the incidence of subsequent lung cancer among breast cancer survivors...
March 17, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28319275/mrf-ann-a-machine-learning-approach-for-automated-er-scoring-of-breast-cancer-immunohistochemical-images
#13
T Mungle, S Tewary, D K DAS, I Arun, B Basak, S Agarwal, R Ahmed, S Chatterjee, C Chakraborty
Molecular pathology, especially immunohistochemistry, plays an important role in evaluating hormone receptor status along with diagnosis of breast cancer. Time-consumption and inter-/intraobserver variability are major hindrances for evaluating the receptor score. In view of this, the paper proposes an automated Allred Scoring methodology for estrogen receptor (ER). White balancing is used to normalize the colour image taking into consideration colour variation during staining in different labs. Markov random field model with expectation-maximization optimization is employed to segment the ER cells...
March 20, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28319069/the-branched-chain-amino-acid-transaminase-1-sustains-growth-of-antiestrogen-resistant-and-er%C3%AE-negative-breast-cancer
#14
V Thewes, R Simon, M Hlevnjak, M Schlotter, P Schroeter, K Schmidt, Y Wu, T Anzeneder, W Wang, P Windisch, M Kirchgäßner, N Melling, N Kneisel, R Büttner, U Deuschle, H P Sinn, A Schneeweiss, S Heck, S Kaulfuss, H Hess-Stumpp, J G Okun, G Sauter, A E Lykkesfeldt, M Zapatka, B Radlwimmer, P Lichter, M Tönjes
Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318328/estrogen-induces-cxcr4-overexpression-and-cxcr4-cxl12-pathway-activation-in-lung-adenocarcinoma-cells-in-vitro
#15
Vianey Rodriguez-Lara, González-Sánchez Ignacio, Marco A Cerbón Cervantes
PURPOSE: This study was designed to investigate whether estradiol is related to the expression of the chemokine receptor CXCR4 and its activation in lung adenocarcinoma in vitro, since lung adenocarcinomas from premenopausal women have shown high levels of CXCR4, and this expression has been associated with worse prognosis and poor survival. METHODS: The effect of 17-β-estradiol (E2) (0.03 nM-10 nM) on CXCR4 expression was analyzed in lung adenocarcinoma cell lines (SK-LU-1, H1435, H23, A549) by immunofluorescence after 24 and 72-h poststimulation...
March 20, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28317066/er%C3%AE-and-gnrh-co-localize-in-the-hypothalamic-neurons-of-the-south-american-plains-vizcacha-lagostomus-maximus-rodentia-caviomorpha
#16
Pablo Ignacio Felipe Inserra, Santiago Elías Charif, Noelia Paula Di Giorgio, Lucía Saucedo, Alejandro Raúl Schmidt, Nicolas Fraunhoffer, Julia Halperin, María Constanza Gariboldi, Noelia Paola Leopardo, Victoria Lux-Lantos, Candela Rocío Gonzalez, Alfredo Daniel Vitullo, Verónica Berta Dorfman
Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal axis. Estradiol (E2) affects GnRH synthesis and delivery. Hypothalamic estrogen receptors (ER) modulate GnRH expression acting as transcription factors. The South American plains vizcacha, Lagostomus maximus, is able to ovulate up to 800 oocytes per reproductive cycle, and shows continuous folliculogenesis with pre-ovulatory follicle formation and an ovulatory event at mid-gestation. The aim of this work was to analyze the hypothalamic expression of ER in the vizcacha at different gestational time-points, and its relationship with GnRH expression, serum luteinizing hormone (LH) and E2...
March 19, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28316975/role-of-estrogens-in-the-size-of-neuronal-somata-of-paravaginal-ganglia-in-ovariectomized-rabbits
#17
Laura G Hernández-Aragón, Verónica García-Villamar, María de Los Ángeles Carrasco-Ruiz, Leticia Nicolás-Toledo, Arturo Ortega, Estela Cuevas-Romero, Margarita Martínez-Gómez, Francisco Castelán
We aimed to determine the role of estrogens in modulating the size of neuronal somata of paravaginal ganglia. Rabbits were allocated into control (C), ovariectomized (OVX), and OVX treated with estradiol benzoate (OVX + EB) groups to evaluate the neuronal soma area; total serum estradiol (E2) and testosterone (T) levels; the percentage of immunoreactive (ir) neurons anti-aromatase, anti-estrogen receptor (ERα, ERβ) and anti-androgen receptor (AR); the intensity of the immunostaining anti-glial cell line-derived neurotrophic factor (GDNF) and the GDNF family receptor alpha type 1 (GFRα1); and the number of satellite glial cells (SGCs) per neuron...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28316229/mucinous-carcinoma-with-extensive-signet-ring-cell-differentiation-a-case-report
#18
Hye Min Kim, Eun Kyung Kim, Ja Seung Koo
Breast cancers that present with mucin include mucinous carcinoma and carcinoma with signet ring cell differentiation. The former shows extracellular mucin and the latter shows abundant intracellular mucin. Here, we report a case of breast cancer showing both extracellular mucin and extensive signet ring cell differentiation due to abundant intracellular mucin. Unlike mucinous carcinoma, this case had the features of high-grade nuclear pleomorphism, high mitotic index, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor-2 positivity, and ductal type with positivity for E-cadherin...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28315687/-10-gingerol-a-major-phenolic-constituent-of-ginger-root-induces-cell-cycle-arrest-and-apoptosis-in-triple-negative-breast-cancer-cells
#19
Megan M Bernard, Jason R McConnery, David W Hoskin
The ginger rhizome is rich in bioactive compounds, including [6]-gingerol, [8]-gingerol, and [10]-gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on [6]-gingerol. In this study, we compared [10]-gingerol with [8]-gingerol and [6]-gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that [10]-gingerol was more potent than [6]-gingerol and at least as potent as [8]-gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth...
March 15, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28315628/association-of-estrogen-receptor-alpha-polymorphisms-with-symptoms-of-autism-among-chinese-han-children
#20
(no author information available yet)
OBJECTIVES: Autism has a significant sex difference. This implies that the sex hormones might have effect on autism. Estrogens play an important role in early nervous system development and sex differentiation through estrogen receptors in brain. Thus, we tested the hypothesis that estrogen receptor alpha (ESR1) gene affects the pathogenesis of autism and related symptoms. METHODS: Genotypes of rs11155819 and rs2234693 were determined in boys with autism and normal boys from Chinese Han population...
November 19, 2016: Neuro Endocrinology Letters
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