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https://www.readbyqxmd.com/read/29220789/new-estrogen-receptor-antagonists-3-20-dihydroxy-19-norpregna-1-3-5-10-trienes-synthesis-molecular-modeling-and-biological-evaluation
#1
Yury V Kuznetsov, Inna S Levina, Alexander M Scherbakov, Olga E Andreeva, Irina V Fedyushkina, Andrey S Dmitrenok, Alexander S Shashkov, Igor V Zavarzin
New estrogen receptor α (ERα) antagonists - 3,20-dihydroxy-19-norpregna-1,3,5(10)-trienes containing an additional carbocyclic ring D' at the 16α,17α positions - were synthesized. The effects of the new compounds on the MCF-7 breast cancer cells and ERα activation were investigated. All the steroids studied were synthesized starting from estrone methyl ether. The scaffold of compounds containing the six-membered ring D' was constructed via the Diels-Alder reaction of butadiene with 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one 5...
November 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29219004/predictors-of-malignancy-in-endometrial-polyps-study-of-421-women-with-postmenopausal-bleeding
#2
A Ghoubara, S Sundar, A A A Ewies
OBJECTIVE: There is lack of consensus as whether benign-looking endometrial polyps should be removed in postmenopausal women. To help inform clinical practice, this study was conducted to quantify the prevalence and identify the predictors of hyperplasia and cancer in polyps. METHODS: The data of 2625 consecutive women attending a postmenopausal bleeding clinic were collected prospectively in a UK teaching hospital between January 2011 and December 2015. Of them, 421 (16%) women with hysteroscopically benign-looking endometrial polyps with normal background endometrium were included...
December 8, 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/29212856/tamoxifen-resistance-in-breast-cancer-is-regulated-by-the-ezh2-er%C3%AE-greb1-transcriptional-axis
#3
Yanming Wu, Zhao Zhang, Mauro E Cenciarini, Cecilia J Proietti, Matias F Amasino, Tao Hong, Mei Yang, Yiji Liao, Huai-Chin Chiang, Virginia Kaklamani, Rinath Jeselsohn, Ratna K Vadlamudi, Tim H-M Huang, Rong Li, Carmine De Angelis, Xiaoyong Fu, Patricia V Elizalde, Rachel Schiff, Myles Brown, Kexin Xu
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents...
December 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/29209900/effect-of-testosterone-on-trpv1-expression-in-a-model-of-orofacial-myositis-pain-in-the-rat
#4
Xiaofeng Bai, Xia Zhang, Qing Zhou
Recent clinical studies have revealed sex differences in response to transient receptor potential vanilloid 1 (TRPV1) agonist-induced pain. However, the mechanism of these differences in TRPV1-related chronic pain remains unclear. In the present study, we investigate the effects of inflammation and gonadal hormones on TRPV1 expression in trigeminal ganglia. Inflammatory pain was modeled by injecting complete Freund's adjuvant (CFA) into the left masseter muscle in rats. TRPV1 mRNA and protein levels in the trigeminal ganglia of male and female rats following CFA injection were assessed...
December 5, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29208952/major-depletion-of-sox2-stem-cells-in-the-adult-pituitary-is-not-restored-which-does-not-affect-hormonal-cell-homeostasis-and-remodelling
#5
Heleen Roose, Benoit Cox, Matteo Boretto, Conny Gysemans, Annelies Vennekens, Hugo Vankelecom
The pituitary gland contains SOX2-expressing stem cells. However, their functional significance remains largely unmapped. We investigated their importance by depleting SOX2+ cells through diphtheria toxin (DT)-mediated ablation. DT treatment of adult Sox2CreERT2/+;R26iDTR/+ mice (after tamoxifen-induced expression of DT receptor in SOX2+ cells) resulted in 80% obliteration of SOX2+ cells in the endocrine pituitary, coinciding with reduced pituisphere-forming activity. Counterintuitively for a stem cell population, the SOX2+ cell compartment did not repopulate...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207335/tamoxifen-a-pioneering-drug-an-update-on-the-therapeutic-potential-of-tamoxifen-derivatives
#6
REVIEW
Shagufta, Irshad Ahmad
Tamoxifen (ICI 46 474), trans-1-(4-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene, is the most commonly used drug for the treatment of estrogen receptor positive breast cancer and has been saving lives worldwide for the past four decades. Tamoxifen is considered a pioneering drug due to its ubiquitous use in both treatment and chemoprevention of breast cancer and also for research addressing novel selective estrogen receptor modulators (SERMs). Tamoxifen is cost effective, lifesaving, and devoid of major side effects in the majority of patients...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29207119/ezh2-inhibition-sensitizes-tamoxifen%C3%A2-resistant-breast-cancer-cells-through-cell-cycle-regulation
#7
Si Chen, Fan Yao, Qinghuan Xiao, Qiannan Liu, Yikun Yang, Xuejuan Li, Guanglie Jiang, Takayoshi Kuno, Yue Fang
Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. However, it remains unclear whether EZH2 contributes to tamoxifen resistance in breast cancer. In the present study, the role of EZH2 in tamoxifen resistance in MCF‑7 cells was investigated. EZH2 was overexpressed in MCF‑7 tamoxifen‑resistant (MCF‑7 TamR) cells...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206871/clopidogrel-in-a-combined-therapy-with-anticancer-drugs-effect-on-tumor-growth-metastasis-and-treatment-toxicity-studies-in-animal-models
#8
Agnieszka Denslow, Marta Świtalska, Joanna Jarosz, Diana Papiernik, Kseniia Porshneva, Marcin Nowak, Joanna Wietrzyk
Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely prescribed for patients with cardiovascular diseases. In addition to antiplatelet activity, antiplatelet agents possess anticancer and antimetastatic properties. Contrary to this, results of some studies have suggested that the use of clopidogrel and other thienopyridines accelerates the progression of breast, colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate the efficacy of clopidogrel and various anticancer agents as a combined treatment using mouse models of breast, colorectal, and prostate cancer...
2017: PloS One
https://www.readbyqxmd.com/read/29205609/effect-of-tamoxifen-on-fibrosis-collagen-content-and-transforming-growth-factor-%C3%AE-1-%C3%AE-2-and-%C3%AE-3-expression-in-common-bile-duct-anastomosis-of-pigs
#9
Orlando Hiroshi Kiono Siqueira, Karen Jesus Oliveira, Angela Cristina Gouvêa Carvalho, Antonio Claudio Lucas da Nóbrega, Renata Frauches Medeiros, Bruno Felix-Patrício, Fábio Otero Áscoli, Beni Olej
End-to-end anastomosis in the treatment for bile duct injury during laparoscopic cholecystectomy has been associated with stricture formation. The aim of this study was to experimentally investigate the effect of oral tamoxifen (tmx) treatment on fibrosis, collagen content and transforming growth factor-β1, -β2 and -β3 expression in common bile duct anastomosis of pigs. Twenty-six pigs were divided into three groups [sham (n = 8), control (n = 9) and tmx (n = 9)]. The common bile ducts were transected and anastomosed in the control and tmx groups...
December 4, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/29205077/forty-years-of-landmark-trials-undertaken-by-the-danish-breast-cancer-cooperative-group-dbcg-nationwide-or-in-international-collaboration
#10
Bent Ejlertsen, Birgitte Vrou Offersen, Jens Overgaard, Peer Christiansen, Maj-Britt Jensen, Niels Kroman, Ann Søgaard Knoop, Henning Mouridsen
BACKGROUND: Over the past 40 years the Danish Breast Cancer Cooperative Group (DBCG) has made significant contributions to improve outcome and to make treatment of patients with early breast cancer more tolerable through nationwide and international trials evaluating loco-regional and systemic treatments. These trials have been instrumental to establish standards for the treatment of early breast cancer. METHODS: The DBCG 82 trials had a global impact by documenting that the significant gain in loco-regional recurrence from postmastectomy radiation added to systemic therapy was associated with a reduction in distant recurrence and mortality in high-risk pre- and postmenopausal patients...
December 5, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29202630/concurrent-new-drug-prescriptions-and-prognosis-of-early-breast-cancer-studies-using-the-danish-breast-cancer-group-clinical-database
#11
Deirdre Cronin-Fenton, Timothy L Lash, Thomas P Ahern, Per Damkier, Peer Christiansen, Bent Ejlertsen, Henrik T Sørensen
BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health. METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence...
December 5, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29202611/aurora-kinase-a-as-a-possible-marker-for-endocrine-resistance-in-early-estrogen-receptor-positive-breast-cancer
#12
Anne E Lykkesfeldt, Benedikte R Iversen, Maj-Britt Jensen, Bent Ejlertsen, Anita Giobbie-Hurder, Birgit E Reiter, Tove Kirkegaard, Birgitte B Rasmussen
BACKGROUND: Cell culture studies have disclosed that the mitotic Aurora kinase A is causally involved in both tamoxifen and aromatase inhibitor resistant cell growth and thus may be a potential new marker for endocrine resistance in the clinical setting. MATERIAL AND METHODS: Archival tumor tissue was available from 1323 Danish patients with estrogen receptor (ER) positive primary breast cancer, who participated in the Breast International Group (BIG) 1-98 trial, comparing treatment with tamoxifen and letrozole and both in a sequence...
December 4, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29202370/endocrine-effects-after-ozonation-of-tamoxifen
#13
Oliver Knoop, Fabian Itzel, Jochen Tuerk, Holger V Lutze, Torsten C Schmidt
Ozonation is used as additional wastewater treatment option to remove recalcitrant micropollutants. It also removes the estrogenic activity found in wastewater but not always the anti-estrogenic activity. This can be explained by an incomplete removal of anti-estrogenic micropollutants or by formation of transformation products (TPs) which retain the activity. The present study investigates the degradation of the anti-estrogenic pharmaceutical tamoxifen in pure water, regarding TP formation and related anti-estrogenic effect using Arxula adeninivorans yeast estrogen screen (A-YES)...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29200666/prevention-of-memory-impairment-and-neurotrophic-factors-increased-by-lithium-in-wistar-rats-submitted-to-pneumococcal-meningitis-model
#14
Lutiana R Simões, Roberta R E S Abreu, Jaqueline S Generoso, Jéssica A Goularte, Allan Collodel, Vijayasree Vayalanellore Giridharan, Anitha Christy Sigamani Arumanayagam, Samira S Valvassori, João Quevedo, Tatiana Barichello
The aim of this study was to investigate the effects of lithium on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) expression in the hippocampus and on memory in experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a neuroprotective agent with many effects on the brain. In this study, animals received either artificial cerebrospinal fluid or Streptococcus pneumoniae suspension at a concentration of 5 × 109 CFU/mL...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29199129/evaluating-estrogenic-and-anti-estrogenic-effect-of-endocrine-disrupting-chemicals-edcs-by-zebrafish-danio-rerio-embryo-based-vitellogenin-1-vtg1-mrna-expression
#15
Minjie Chen, Jie Zhang, Shaochen Pang, Chang Wang, Ling Wang, Yonghua Sun, Maoyong Song, Yong Liang
By measuring the vitellogenin 1 (vtg1) expression through quantitative PCR and in situ hybridization, we used the zebrafish embryo as an in vivo model to access the estrogenic or anti-estrogenic effects of several endocrine disrupting chemicals (EDCs), such as natural estrogen 17β-estradiol (E2), estriol (E3), synthetic hormones including diethylstilbestrol (DES), 4-octyl phenol (OP), bisphenol A (BPA), tamoxifen (TMX) and 3-(2,3-dibromopropyl) isocyanurate (TBC). According to our data, the estrogenic effect of the tested chemicals was ranked as: DES>E2>E3>OP > BPA, which is consistent with various in vivo and in vitro models...
November 30, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29197846/severe-recurrent-hypothermia-in-an-elderly-patient-with-refractory-mania-associated-with-atypical-antipsychotic-valproic-acid-and-oxcarbazepine-therapy
#16
Oluwadamilare O Ajayi, Suzanne Holroyd
Hypothermia is a rare but serious condition that has been associated with various psychiatric medications. We present a 76-year-old woman with refractory mania who developed multiple episodes of severe hypothermia associated with several psychiatric medications including olanzapine, quetiapine, valproic acid and oxcarbazepine. These episodes resolved following discontinuation of the agents. The patient had never experienced hypothermia before, despite having been on these or similar agents for many years. With traditional treatments for mania not feasible, other medications were used to treat her including lithium, clonazepam, gabapentin and the novel protein kinase c inhibitor tamoxifen...
December 2, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29190923/prognostic-values-of-distinct-cbx-family-members-in-breast-cancer
#17
Yuan-Ke Liang, Hao-Yu Lin, Chun-Fa Chen, De Zeng
Chromobox (CBX) family proteins are canonical components in polycomb repressive complexes 1 (PRC1), with epigenetic regulatory function and transcriptionally repressing target genes via chromatin modification. A plethora of studies have highlighted the function specifications among CBX family members in various cancer, including lung cancer, colon cancer and breast cancer. Nevertheless, the functions and prognostic roles of distinct CBX family members in breast cancer (BC) remain elusive. In this study, we reported the prognostic values of CBX family members in patients with BC through analysis of a series of databases, including CCLE, ONCOMINE, Xena Public Data Hubs, and Kaplan-Meier plotter...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190716/suppression-of-cancer-stemness-by-upregulating-ligand-of-numb-protein-x1-in-colorectal-carcinoma
#18
Lin Ma, Lan Wang, Yating Shan, Muhammad Nafees, Elshoura Ihab, Ruhui Zhang, Fangjun Wang, Wu Yin
Cancer stem-like cells (CSCs) have been reported to play major roles in tumorigenesis, tumor relapse, and metastasis after therapy against colorectal carcinoma (CRC). Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb. Although several studies indicate LNX1 could be a potential suppressor of cancer diseases, the functions of LNX1 in mediating cancer stemness remain poorly understood...
2017: PloS One
https://www.readbyqxmd.com/read/29189180/design-synthesis-and-anti-breast-cancer-activity-of-some-novel-substituted-isoxazoles-as-anti-breast-cancer-agent
#19
Santosh N Mokale, Nikhil S Sakle, Swati A Bhavale, Deepak K Lokwani, Vishakha Shelke
A novel series of isoxazole (S21-S30) derivatives were designed, synthesized and screened for their anticancer activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. The synthesized derivative has ability to inhibit the growth of the human breast cancer cell line at low concentrations. In-vivo anticancer activity was performed on virgin female sprague dawley rats. The result shows that the compound S23 has more selectivity and marked estrogen modulator activity than the standard tamoxifen...
November 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29187823/voluntary-exercise-improves-cardiac-function-and-prevents-cardiac-remodeling-in-a-mouse-model-of-dilated-cardiomyopathy
#20
Robin Deloux, Damien Vitiello, Nathalie Mougenot, Philippe Noirez, Zhenlin Li, Mathias Mericskay, Arnaud Ferry, Onnik Agbulut
Objective: Despite the indubitable beneficial effect of exercise to prevent of cardiovascular diseases, there is still a lack of studies investigating the impact of exercise in non-ischemic dilated cardiomyopathy. Here, we investigated the impact of voluntary exercise on cardiac function in a mouse model of non-ischemic dilated cardiomyopathy (αMHC-MerCreMer:Sf/Sf), induced by cardiac-specific inactivation of the Serum Response Factor. Materials and Methods: Seven days after tamoxifen injection, 20 αMHC-MerCreMer:Sf/Sf mice were assigned to sedentary (n = 8) and exercise (n = 12) groups...
2017: Frontiers in Physiology
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