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https://www.readbyqxmd.com/read/29458080/transcriptomic-and-phenotypic-profiling-in-developing-zebrafish-exposed-to-thyroid-hormone-receptor-agonists
#1
Derik E Haggard, Pamela D Noyes, Katrina M Waters, Robert L Tanguay
There continues to be a need to develop in vivo high-throughput screening (HTS) and computational methods to screen chemicals for interaction with the estrogen, androgen, and thyroid pathways and as complements to in vitro HTS assays. This study explored the utility of an embryonic zebrafish HTS approach to identify and classify endocrine bioactivity using phenotypically-anchored transcriptome profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of animals exposed...
February 16, 2018: Reproductive Toxicology
https://www.readbyqxmd.com/read/29456719/estrogen-receptor-%C3%AE-promoter-methylation-is-a-biomarker-for-outcome-prediction-of-cisplatin-resistance-in-triple-negative-breast-cancer
#2
Junnan Xu, Tao Sun, Xiangyu Guo, Yan Wang, Mingxi Jing
A number of previous studies have indicated the presence of a link between estrogen receptor-α (ERα) methylation and triple-negative breast cancer (TNBC). However, the association between ERα methylation and drug resistance during the treatment of TNBC remains unclear. Methylation-specific polymerase chain reaction was used to investigate the methylation of ERα in the genomic DNA of 35 patients with TNBC who were defined as cisplatin-based chemotherapy-resistant using chemosensitivity testing. Survival probabilities by covariates were assessed using Kaplan-Meier estimator survival analysis and Cox's proportional hazards models, adjusting for age, menopausal status, tumor size, lymph node metastasis and ERα promoter DNA methylation...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456471/neoadjuvant-chemotherapy-exerts-selection-pressure-towards-luminal-phenotype-breast-cancer
#3
Giulia Galli, Giacomo Bregni, Stefano Cavalieri, Luca Porcu, Paolo Baili, Amash Hade, Francesca Di Salvo, Milena Sant, Roberto Agresti, Massimiliano Gennaro, Secondo Folli, Maria C De Santis, Biagio Paolini, Maria L Carcangiu, Filippo de Braud, Serena Di Cosimo
Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29455641/circadian-pathway-genetic-variation-and-cancer-risk-evidence-from-genome-wide-association-studies
#4
Simone Mocellin, Saveria Tropea, Clara Benna, Carlo Riccardo Rossi
BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). METHODS: Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method...
February 19, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29455003/combinatorial-strategy-of-epigenetic-and-hormonal-therapies-a-novel-promising-approach-for-treating-advanced-prostate-cancer
#5
Tarek K Motawi, Hebatallah A Darwish, Iman Diab, Maged W Helmy, Mohamed Noureldin
AIMS: Estrogens act as key factors in prostate biology, cellular proliferation and differentiation as well as cancer development and progression. The expression of estrogen receptor (ER)-β appears to be lost during prostate cancer progression through hypermethylation mechanism. Epigenetic drugs such as 5-aza-2'-deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring ERβ expression in prostate cancer cells. This study was designed to explore the potential anti-carcinogenic effects resulting from re-expressing ERβ1 using 5-AZAC and/or TSA, followed by its stimulation with Diarylpropionitrile (DPN), a selective ERβ1 agonist, in prostate cancer cell line PC-3...
February 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29454903/estrogen-receptor-alpha-isoforms-are-the-main-estrogen-receptors-expressed-in-non-small-cell-lung-carcinoma
#6
Vasiliki Pelekanou, Eleftheria Anastasiou, Efstathia Bakogeorgou, George Notas, Marilena Kampa, Rolando Garcia-Milian, Katerina Lavredaki, Eleni Moustou, Georgia Chinari, Petroula Arapantoni, Anthony O'Grady, Vassilios Georgoulias, Andreas Tsapis, Efstathios N Stathopoulos, Elias Castanas
The expression profile of estrogen receptors (ER) in Non-Small Cell Lung Carcinoma (NSCLC) remains contradictory. Here we investigated protein and transcriptome expression of ERα wild type and variants. Tissue Micro-Arrays of 200 cases of NSCLC (paired tumor/non-tumor) were assayed by immunohistochemistry using a panel of ERα antibodies targeting different epitopes (HC20, 6F11, 1D5, ERα36 and ERα17p). ERβ epitopes were also examined for comparison. In parallel we conducted a probe-set mapping (Affymetrix HGU133 plus 2 chip) meta-analysis of 12 NSCLC tumor public transcriptomic studies (1418 cases) and 39 NSCLC cell lines...
February 15, 2018: Steroids
https://www.readbyqxmd.com/read/29454887/metabolomic-analysis-uncovered-an-association-of-serum-phospholipid-levels-with-estrogen-induced-mammary-tumors-in-female-aci-seg-rats
#7
Yoshinori Okamoto, Akira Aoki, Koji Ueda, Hideto Jinno
Estrogen is reported to be involved in mammary tumorigenesis. To unveil metabolic signatures for estrogen-induced mammary tumorigenesis, we carried out serum metabolomic analysis in an estrogen-induced mammary tumor model, female August Copenhagen-Irish/Segaloff (ACI/Seg) rats, using liquid chromatography-mass spectrometry. In contrast to the control group, all rats with an implanted 17β-estradiol (E2) pellet developed mammary tumors during this experiment. E2 treatment significantly suppressed body weight gain...
February 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29453570/molecular-mechanisms-and-signaling-pathways-involved-in-the-nutritional-support-of-spermatogenesis-by-sertoli-cells
#8
Luís Crisóstomo, Marco G Alves, Agostina Gorga, Mário Sousa, María F Riera, María N Galardo, Silvina B Meroni, Pedro F Oliveira
Sertoli cells play a central role in spermatogenesis. They maintain the blood-testis barrier, an essential feature of seminiferous tubules which creates the proper environment for the occurrence of the spermatogenesis. However, this confinement renders germ cells almost exclusively dependent on Sertoli cells' nursing function and support. Throughout spermatogenesis, differentiating sperm cells become more specialized, and their biochemical machinery is insufficient to meet their metabolic demands. Although the needs are not the same at all differentiation stages, Sertoli cells are able to satisfy their needs...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453409/a-potential-prognostic-long-noncoding-rna-signature-to-predict-recurrence-among-er-positive-breast-cancer-patients-treated-with-tamoxifen
#9
Kang Wang, Jie Li, Yong-Fu Xiong, Zhen Zeng, Xiang Zhang, Hong-Yuan Li
Limited predictable long noncoding RNA (lncRNA) signature was reported in tamoxifen resistance among estrogen receptor (ER)-positive breast cancer (BC) patients. The aim of this study was to identify and assess prognostic lncRNA signature to predict recurrence among ER-positive BC patients treated with tamoxifen. Cohorts from Gene Expression Omnibus (GEO) (n = 298) and The Cancer Genome Atlas (TCGA) (n = 160) were defined as training and validation cohort, respectively. BC relapse associated lnRNAs was identify within training cohort, and the predictable value of recurrence was assessed in both cohorts...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#10
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452237/a-redox-sensitive-signaling-pathway-mediates-pro-angiogenic-effect-of-chlordecone-via-estrogen-receptor-activation
#11
Eid Alabed Alibrahim, Ramaroson Andriansitohaina, Kévin Hardonnière, Raffaella Soleti, Sébastien Faure, Gilles Simard
AIM: Chlordecone is able to induce pro-angiogenic effect through an estrogen receptor (ERα) pathway involving NO release and VEGF. The present study aimed to determine the molecular mechanisms by which chlordecone promotes angiogenesis in human endothelial cells. RESULTS: High but not low concentration of chlordecone increased mitochondrial respiratory capacity and mitochondrial DNA content in endothelial cells. The ROS scavenger MnTMPyP was able to prevent the increase of both VEGF expression and capillary length induced by chlordecone...
February 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29452160/orchiectomy-and-letrozole-differentially-regulate-synaptic-plasticity-and-spatial-memory-in-a-manner-that-is-mediated-by-src-1-in-the-hippocampus-of-male-mice
#12
Jikai Zhao, Chen Bian, Mengying Liu, Yangang Zhao, Tao Sun, Fangzhou Xing, Jiqiang Zhang
Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity...
February 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29452074/differential-control-of-appetitive-and-consummatory-sexual-behavior-by-neuroestrogens-in-male-quail
#13
REVIEW
Charlotte A Cornil, Gregory F Ball, Jacques Balthazart
Estrogens exert pleiotropic effects on multiple physiological and behavioral traits including sexual behavior. These effects are classically mediated via binding to nuclear receptors and subsequent regulation of target gene transcription. Estrogens also affect neuronal activity and cell-signaling pathways via faster, membrane-initiated events. Although the distinction between appetitive and consummatory aspects of sexual behavior has been criticized, this distinction remains valuable in that it facilitates the causal analysis of certain behavioral systems...
February 13, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29451783/sufex-click-chemistry-enabled-late-stage-drug-functionalization
#14
Zilei Liu, Jie Li, Suhua Li, Gencheng Li, K Barry Sharpless, Peng Wu
Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the S VI -F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products...
February 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29451493/er%C3%AE-promotes-murine-hematopoietic-regeneration-through-the-ire1%C3%AE-mediated-unfolded-protein-response
#15
Richard H Chapple, Tianyuan Hu, Yu-Jung Tseng, Lu Liu, Ayumi Kitano, Victor Luu, Kevin A Hoegenauer, Takao Iwawaki, Qing Li, Daisuke Nakada
Activation of the unfolded protein response (UPR) sustains protein homeostasis (proteostasis) and plays a fundamental role in tissue maintenance and longevity of organisms. Long-range control of UPR activation has been demonstrated in invertebrates, but such mechanisms in mammals remain elusive. Here, we show that the female sex hormone estrogen regulates the UPR in hematopoietic stem cells (HSCs). Estrogen treatment increases the capacity of HSCs to regenerate the hematopoietic system upon transplantation and accelerates regeneration after irradiation...
February 16, 2018: ELife
https://www.readbyqxmd.com/read/29450827/progression-free-survival-results-in-postmenopausal-asian-women-subgroup-analysis-from-a-phase-iii-randomized-trial-of-fulvestrant-500-mg-vs-anastrozole-1-mg-for-hormone-receptor-positive-advanced-breast-cancer-falcon
#16
Shinzaburo Noguchi, Matthew J Ellis, John F R Robertson, Jackie Thirlwell, Mehdi Fazal, Zhimin Shao
BACKGROUND: The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study...
February 15, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29450494/comparison-of-the-performance-of-6-prognostic-signatures-for-estrogen-receptor-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#17
Ivana Sestak, Richard Buus, Jack Cuzick, Peter Dubsky, Ralf Kronenwett, Carsten Denkert, Sean Ferree, Dennis Sgroi, Catherine Schnabel, Frederick L Baehner, Elizabeth Mallon, Mitch Dowsett
Importance: Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. Objective: To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years. Design, Setting, and Participants: This retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)-negative breast cancer...
February 15, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29449724/angiomyofibroblastoma-of-the-spermatic-cord-a-case-report
#18
L Bouhajja, S A Rammeh, S Sayari, R Zermani, F Farah
Angiomyofibroblastoma (AMF) is a rare benign mesenchymal tumor with tendency to arise in the lower genital tract of middleaged women, predominately in the vulva. A few cases of AMF in males have been reported involving the scrotum, perineum or spermatic cord. We report a new case of AMF arising in the right inguinal region of a 27-year-old man. The tumor was well-circumscribed, myxoid and measured 30 mm in maximum dimension. On microscopic examination, the tumor was composed of spindle cells without atypia and with less than one mitosis figure per 10 high-power fields...
December 2017: Pathologica
https://www.readbyqxmd.com/read/29449047/validation-and-update-of-a-lymph-node-metastasis-prediction-model-for-breast-cancer
#19
Si-Qi Qiu, Merel Aarnink, Marissa C van Maaren, Monique D Dorrius, Arkajyoti Bhattacharya, Jeroen Veltman, Caroline A H Klazen, Jan H Korte, Susanne H Estourgie, Pieter Ott, Wendy Kelder, Huan-Cheng Zeng, Hendrik Koffijberg, Guo-Jun Zhang, Gooitzen M van Dam, Sabine Siesling
PURPOSE: This study aimed to validate and update a model for predicting the risk of axillary lymph node (ALN) metastasis for assisting clinical decision-making. METHODS: We included breast cancer patients diagnosed at six Dutch hospitals between 2011 and 2015 to validate the original model which includes six variables: clinical tumor size, tumor grade, estrogen receptor status, lymph node longest axis, cortical thickness and hilum status as detected by ultrasonography...
January 17, 2018: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29448043/estrogen-serum-concentration-affects-blood-immune-cell-composition-and-polarization-in-human-females-under-controlled-ovarian-stimulation
#20
Pardes Habib, Daniela Dreymueller, Benjamin Rösing, Hannes Botung, Alexander Slowik, Adib Zendedel, Shahin Habib, Stefanie Hoffmann, Cordian Beyer
Estrogens modulate the immune system and possess anti-inflammatory properties. In line, immune cells express a variety of estrogen receptors (ER) including ER-alpha and -beta. In the present study, we examined the influence of 17beta-estradiol (E2) serum concentrations on blood leukocyte composition and their ex vivo polarization/activation status by FACS analysis in sub-fertile human females under controlled ovarian stimulation (COS). Using a set of cell-type and polarization-specific markers, we demonstrate that increased 17ß-estradiol (E2) serum concentrations yield an overall increase in leukocytes, neutrophils and monocytes but decreased lymphocytes...
February 12, 2018: Journal of Steroid Biochemistry and Molecular Biology
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