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https://www.readbyqxmd.com/read/29789325/genomic-epidemiologic-evidence-that-estrogens-promote-breast-cancer-development
#1
Fritz F Parl, Philip S Crooke, W Dale Plummer, William D Dupont
BACKGROUND: Estrogens are a prime risk factor for breast cancer yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Since estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17ß-estradiol (E2), and the estrogen receptor, ESR1 (ERα)...
May 22, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29784731/transformed-follicular-lymphoma-tfl-predicts-outcome-in-advanced-endometrial-cancer
#2
Senn Wakahashi, Fumi Kawakami, Kanako Wakahashi, Kentaro Minagawa, Keitaro Matsuo, Yoshio Katayama, Hideto Yamada, Toshimitsu Matsui, Tamotsu Sudo
BACKGROUND: Transformed follicular lymphoma (TFL, ZC3H12D) was identified, as a candidate tumor suppressor gene that contributes to cell-cycle arrest through regulation of Rb phosphorylation, but the clinical impact of TFL is unknown. The goal of this study was to evaluate the prognostic significance of TFL expression in advanced endometrial cancer. METHODS: Tissue samples were obtained from 103 patients with FIGO stage III-IV endometrial cancer. Associations between TFL expression and outcomes were evaluated using the Kaplan-Meier method and multivariate Cox proportional-hazards regression models...
May 21, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29780747/precision-medicine-in-hormone-receptor-positive-breast-cancer
#3
REVIEW
Azadeh Nasrazadani, Roby A Thomas, Steffi Oesterreich, Adrian V Lee
In recent decades, breast cancer has become largely manageable due to successes with hormone receptor targeting. Hormone receptor-positive tumors have favorable outcomes in comparison to estrogen receptor (ESR1, ER)/progesterone receptor-negative tumors given the targetable nature of these tumors, as well as their inherently less aggressive character. Nonetheless, treatment resistance is frequently encountered due to a variety of mechanisms, including ESR1 mutations and loss of ER expression. A new era of precision medicine utilizes a range of methodologies to allow real-time analysis of individual genomic signatures in metastases and liquid biopsies with the goal of finding clinically actionable targets...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29770127/temporal-expression-patterns-of-genes-related-to-sex-steroid-action-in-sexually-dimorphic-nuclei-during-puberty
#4
Moeko Kanaya, Masahiro Morishita, Shinji Tsukahara
Sex steroids play a major role in sexually dimorphic brain development during not only the perinatal period but also the pubertal period. We previously showed that, in male mice, the estrogen receptor-α ( Esr1 ) and aromatase ( Cyp19a1 ) genes are essential to the sexually dimorphic formation of the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), but the estrogen receptor-β ( Esr2 ) gene is not necessary. We also showed that the androgen receptor ( Ar ) gene is essential to the sexually dimorphic formation of the BNSTp...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769099/circulating-esr1-mutations-at-the-end-of-aromatase-inhibitor-adjuvant-treatment-and-after-relapse-in-breast-cancer-patients
#5
Violette Allouchery, Ludivine Beaussire, Anne Perdrix, David Sefrioui, Laetitia Augusto, Cécile Guillemet, Nasrin Sarafan-Vasseur, Frédéric Di Fiore, Florian Clatot
BACKGROUND: Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. METHODS: This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29763890/mir-301a-3p-suppresses-estrogen-signaling-by-directly-inhibiting-esr1-in-er%C3%AE-positive-breast-cancer
#6
Sandra Lettlova, Veronika Brynychova, Jan Blecha, David Vrana, Magdalena Vondrusova, Pavel Soucek, Jaroslav Truksa
BACKGROUND/AIMS: MiRNA-301a-3p is an oncogenic miRNA whose expression is associated with tumor development, metastases and overall poor prognosis. Estrogen receptor α (ERα) is one of the estrogen hormone-activated transcription factors, which regulates a large number of genes and is involved in the mammary gland development. Expression of ERα is considered to be a good indicator for endocrine therapy and breast cancer survival. Loss of ERα in breast cancer patients indicates invasiveness and poor prognosis...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29758295/systematic-bioinformatic-approaches-reveal-novel-gene-expression-signatures-associated-with-acquired-resistance-to-egfr-targeted-therapy-in-lung-cancer
#7
Marjan Mojtabavi Naeini, Manoochehr Tavassoli, Kamran Ghaedi
OBJECTIVES: Human non-small cell lung cancer (NSCLC) that harbors activating mutations in epidermal growth factor receptor (EGFR) initially responds to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib but eventually tumor cells acquire resistance. To date, several gene expression profiles have been reported in TKIs-resistant EGFR-mutant NSCLC. The objective of this study is to identify robust gene expression signatures, biological processes, and promising overcoming targets for TKIs-resistant EGFR-mutant NSCLC...
May 11, 2018: Gene
https://www.readbyqxmd.com/read/29753772/increase-in-hyaluronic-acid-degradation-decreases-the-expression-of-estrogen-receptor-alpha-in-mcf7-breast-cancer-cell-line
#8
Vincent Hanoux, Judith Eguida, Emmanuelle Fleurot, Jérôme Levallet, Pierre-Jacques Bonnamy
The loss of estrogen receptor α (ERα) expression in breast cancer constitutes a major hallmark of tumor progression to metastasis and is generally correlated to a strong increase in Hyaluronic Acid (HA) turnover. The aim of our study was to search for a putative link between these two major events of breast cancer progression in the estrogen receptor-positive (ER+) MCF7 breast cancer cell line. The increase in HA turnover was performed by stable overexpression of the standard CD44 (CD44S) isoform and also by treatment with exogenous Hyaluronidase (Hyal) to allow an increase in HA catabolism...
May 10, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29753248/embryonic-exposure-to-benzo-a-pyrene-inhibits-reproductive-capability-in-adult-female-zebrafish-and-correlation-with-dna-methylation
#9
Dongxu Gao, Jing Lin, Kunlin Ou, Ying Chen, Hongbin Li, Qinhua Dai, Zhenni Yu, Zhenghong Zuo, Chonggang Wang
This study was conducted to investigate the effects of embryonic short-term exposure to benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, on ovarian development and reproductive capability in adult female zebrafish. In 1-year-old fish after embryonic exposure to BaP for 96 h, the gonadosomatic indices and the percentage of mature oocytes were significantly decreased in the 0.5, 5 and 50 nmol/L treatments. The spawned egg number, the fertilization rate and the hatching success were significantly reduced, while the malformation rate of the F1 unexposed larvae were increased...
May 9, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29749669/in-silico-analysis-of-single-cell-rna-sequencing-data-from-3-and-7-days-old-mouse-spermatogonial-stem-cells-to-identify-their-differentially-expressed-genes-and-transcriptional-regulators
#10
Sajjad Sisakhtnezhad
Spermatogonial stem cells (SSCs), which are at the basis of spermatogenesis process, are valuable cells with different applications in biotechnology and regenerative medicine. Understanding the molecular basis of SSC self-renewal and differentiation at various developmental stages of the male organism is crucial to find key factors in the SSCs fate and function. Therefore, this study was aimed to use single-cell RNA-sequencing dataset analysis for identification of differentially expressed genes (DEGs) and their regulators in 3 and 7 days old mouse-derived single SSCs (mSSCs)...
May 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29748621/proteomic-profiling-identifies-key-coactivators-utilized-by-mutant-er%C3%AE-proteins-as-potential-new-therapeutic-targets
#11
Leah A Gates, Guowei Gu, Yue Chen, Aarti D Rohira, Jonathan T Lei, Ross A Hamilton, Yang Yu, David M Lonard, Jin Wang, Shu-Ping Wang, David G Edwards, Philip F Lavere, Jiangyong Shao, Ping Yi, Antrix Jain, Sung Yun Jung, Anna Malovannaya, Shunqiang Li, Jieya Shao, Robert G Roeder, Matthew J Ellis, Jun Qin, Suzanne A W Fuqua, Bert W O'Malley, Charles E Foulds
Approximately 75% of breast cancers are estrogen receptor alpha (ERα)-positive and are treatable with endocrine therapies, but often patients develop lethal resistant disease. Frequent mutations (10-40%) in the ligand-binding domain (LBD) codons in the gene encoding ERα (ESR1) have been identified, resulting in ligand-independent, constitutively active receptors. In addition, ESR1 chromosomal translocations can occur, resulting in fusion proteins that lack the LBD and are entirely unresponsive to all endocrine treatments...
May 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29747396/beta-estradiol-regulates-voltage-gated-calcium-channels-and-estrogen-receptors-in-telocytes-from-human-myometrium
#12
Adela Banciu, Daniel Dumitru Banciu, Cosmin Catalin Mustaciosu, Mihai Radu, Dragos Cretoiu, Junjie Xiao, Sanda Maria Cretoiu, Nicolae Suciu, Beatrice Mihaela Radu
Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29746933/postnatal-exposure-to-a-glyphosate-based-herbicide-modifies-mammary-gland-growth-and-development-in-wistar-male-rats
#13
Gabriela A Altamirano, Melisa B Delconte, Ayelen L Gomez, Paola Ingaramo, Verónica L Bosquiazzo, Enrique H Luque, Mónica Muñoz-de-Toro, Laura Kass
Our aim was to evaluate whether postnatal exposure to a glyphosate-based herbicide (GBH) modifies mammary gland development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48 h with either saline solution (vehicle) or 2 mg GBH/kg·bw. On PND21 and PND60, mammary gland and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, mammary gland histology, collagen fiber organization, mast cell infiltration, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expression levels were evaluated...
May 7, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29738667/estrogenic-mechanisms-and-cardiac-responses-following-early-life-exposure-to-bisphenol-a-bpa-and-its-metabolite-4-methyl-2-4-bis-p-hydroxyphenyl-pent-1-ene-mbp-in-zebrafish
#14
John Moreman, Aya Takesono, Maciej Trznadel, Matthew Winter, Alexis Perry, Mark Wood, Nicola Jane Rogers, Tetsuhiro Kudoh, Charles R Tyler
Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack of agreement on its mechanism(s) of action likely stem from comparisons between in vivo and in vitro test systems and potential multiple effects pathways. In rodents, in vivo, metabolic activation of BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported to be up to 1000 times more potent as an estrogen than BPA. We investigated the estrogenic effects and estrogen receptor signaling pathway(s) of BPA and MBP following early life exposure using a transgenic, estrogen responsive (ERE-TG) zebrafish and a targeted morpholino approach to knockdown the three fish estrogen receptor (ER) subtypes...
May 8, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29736566/the-impact-of-esr1-mutations-on-the-treatment-of-metastatic-breast-cancer
#15
REVIEW
Sasha M Pejerrey, Derek Dustin, Jin-Ah Kim, Guowei Gu, Yassine Rechoum, Suzanne A W Fuqua
After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene...
May 7, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29731982/gene-specific-methylation-profiles-in-brca-mutation-positive-and-brca-mutation-negative-male-breast-cancers
#16
Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731970/elevated-seminal-plasma-estradiol-and-epigenetic-inactivation-of-esr1-and-esr2-is-associated-with-cp-cpps
#17
Nils Nesheim, Stuart Ellem, Temuujin Dansranjavin, Christina Hagenkötter, Elena Berg, Rupert Schambeck, Hans-Christian Schuppe, Adrian Pilatz, Gail Risbridger, Wolfgang Weidner, Florian Wagenlehner, Undraga Schagdarsurengin
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation)...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29730265/a-molecular-framework-for-auxin-controlled-homeostasis-of-shoot-stem-cells-in-arabidopsis
#18
Linjie Luo, Jian Zeng, Haijun Wu, Zhaoxia Tian, Zhong Zhao
The classic phytohormone auxin plays essential roles in priming meristematic cell differentiation in the shoot apical meristem to promote lateral organ initiation. Recently, several lines of evidence have suggested that auxin not only is transported to new primordia but also descends in stem cells in the central zone. However, the function of auxin in stem cell regulation has remained elusive. Here, we show that auxin signaling in stem cells is mediated, at least in part, by AUXIN RESPONSE FACTOR5/MONOPTEROS (MP), which directly represses the transcription of DORNROSCHEN/ENHANCER OF SHOOT REGENERATION 1 (DRN/ESR1)...
May 3, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29718092/updated-results-from-monaleesa-2-a-phase-iii-trial-of-first-line-ribociclib-plus-letrozole-versus-placebo-plus-letrozole-in-hormone-receptor-positive-her2-negative-advanced-breast-cancer
#19
G N Hortobagyi, S M Stemmer, H A Burris, Y S Yap, G S Sonke, S Paluch-Shimon, M Campone, K Petrakova, K L Blackwell, E P Winer, W Janni, S Verma, P Conte, C L Arteaga, D A Cameron, S Mondal, F Su, M Miller, M Elmeliegy, C Germa, J O'Shaughnessy
Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. Patients and methods: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2...
April 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29713003/multi-omics-profiling-of-younger-asian-breast-cancers-reveals-distinctive-molecular-signatures
#20
Zhengyan Kan, Ying Ding, Jinho Kim, Hae Hyun Jung, Woosung Chung, Samir Lal, Soonweng Cho, Julio Fernandez-Banet, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Yoon-La Choi, Shibing Deng, Ji-Yeon Kim, Jin Seok Ahn, Ying Sha, Xinmeng Jasmine Mu, Jae-Yong Nam, Young-Hyuck Im, Soohyeon Lee, Woong-Yang Park, Seok Jin Nam, Yeon Hee Park
Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA...
April 30, 2018: Nature Communications
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