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https://www.readbyqxmd.com/read/28814238/structural-insights-for-drugs-developed-for-phospholipase-d-enzymes
#1
Kimberly Stieglitz
BACKGROUND: In recent years human phospholipase D enzymes (PLD1 and PLD2 isozymes) have emerged as drug targets for various diseases such as cardiovascular disease, cancer, infectious diseases and neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The interest in PLD as a drug target is due to the fact that PLD enzymes belong to a superfamily of phospholipases that are essential to intracellular and extracellular signaling. Many bioactive lipid signaling molecules are generated by these enzymes including phosphatidic and lysophosphatidic acid, arachidonic acid, and diacylglycerol (DAG)...
August 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28811679/bisphenol-a-does-not-mimic-estrogen-in-the-promotion-of-the-in-vitro-response-of-murine-dendritic-cells-to-toll-like-receptor-ligands
#2
Marita Chakhtoura, Uma Sriram, Michelle Heayn, Joshua Wonsidler, Christopher Doyle, Joudy-Ann Dinnall, Stefania Gallucci, Rebecca A Roberts
Sex hormones affect immune responses and might promote autoimmunity. Endocrine disrupting chemicals such as bisphenol A (BPA) may mimic their immune effects. Conventional dendritic cells (cDCs) are pivotal initiators of immune responses upon activation by danger signals coming from pathogens or distressed tissues through triggering of the Toll-like receptors (TLRs). We generated in vitro murine cDCs in the absence of estrogens and measured the effects of exogenously added estrogen or BPA on their differentiation and activation by the TLR ligands LPS and CpG...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28810190/design-synthesis-and-biological-evaluation-of-novel-2-methoxyestradiol-analogs-as-dual-selective-estrogen-receptor-modulators-serms-and-antiangiogenic-agents
#3
Kejing Lao, Yejun Wang, Mingqi Chen, Jingjing Zhang, Qidong You, Hua Xiang
2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological evaluation was performed on their anti-proliferative activities against 5 different cell lines. The results indicated that most compounds exhibited good activities, in which compound 24c and 30c showed the best activity with low micromolar IC50 (2.73 μM -7...
August 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28810041/morphologic-and-postoperative-fixation-characteristics-of-the-macular-epiretinal-membrane-in-young-patients-undergoing-surgery
#4
Tian Tian, Chunli Chen, Haiying Jin, Qi Zhang, Yu Xu, Shiyuan Wang, Xiang Zhang, Peiquan Zhao
BACKGROUND AND OBJECTIVE: To describe morphologic characteristics, surgical outcomes, postoperative preferred retinal loci (PRL), and fixation stability of epiretinal membranes (ERMs) in young patients. PATIENTS AND METHODS: This retrospective study analyzed 43 eyes of 41 young patients (age range: 0.8 years to 28 years) with ERMs, which were divided into two groups: secondary ERMs (SERMs; n = 28) and idiopathic ERMs (IERMs; n = 13). All 43 eyes underwent 25-gauge vitrectomy and membrane peeling...
August 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28743853/-new-methods-for-the-evaluation-of-bone-quality-relationship-between-bone-resorption-inhibitors-and-bony-quality
#5
Takashi Nagai, Koji Ishikawa, Takuma Kuroda, Yusuke Oshita, Keizo Sakamoto, Katsunori Inagaki
Bone resorption inhibitors used in Japan are bisphosphonate, selective estrogen receptor modulators(SERMs), denosumab, eldecalcitol, and calcitonin. The structural and material properties of bone quality are important factors in osteoporosis treatment. In contrast to improvements in bone density, those in bone quality are difficult to clinically determine as no simple test is available and changes are difficult to detect. Numerous reports have been published on the mechanisms by which bone resorption inhibitors increase bone density and suppress bone fractures...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28739487/the-ros-mediated-activation-of-il-6-stat3-signaling-pathway-is-involved-in-the-27-hydroxycholesterol-induced-cellular-senescence-in-nerve-cells
#6
Jiao Liu, Yun Liu, Juan Chen, Chunyan Hu, Mengying Teng, Kailin Jiao, Zhaoxia Shen, Dongmei Zhu, Jia Yue, Zhong Li, Yuan Li
The oxysterol 27-hydroxycholesterol (27HC) is a selective estrogen receptor modulator (SERMs), which like endogenous estrogen 17β-estradiol (E2) induces the proliferation of ER-positive breast cancer cells in vitro. Interestingly, the observation that 27HC induces adverse effects in neural system, distinguishing it from E2. It has been suggested that high levels of circulating cholesterol increase the entry of 27HC into the brain, which may induce learning and memory impairment. Based on this evidence, 27HC may be associated with neurodegenerative processes and interrupted cholesterol homeostasis in the brain...
July 21, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28734560/deciding-on-breast-cancer-risk-reduction-the-role-of-counseling-in-individual-decision-making-a-qualitative-study
#7
Sarah B Blakeslee, Worta McCaskill-Stevens, Patricia A Parker, Christine M Gunn, Hanna Bandos, Therese B Bevers, Tracy A Battaglia, Angela Fagerlin, Jacqueline Müller-Nordhorn, Christine Holmberg
OBJECTIVES: The presentation of risks and benefits in clinical practice is common particularly in situations in which treatment recommendations involve trade-offs. The treatment of breast cancer risk with selective estrogen receptor modulators (SERMs) is such a decision. We investigated the influence of health care provider (HCP) counseling on women's decision-making. METHODS: Thirty breast cancer risk counseling sessions were recorded from April 2012-August 2013 at a comprehensive cancer center and at a safety-net, community hospital in the US...
June 27, 2017: Patient Education and Counseling
https://www.readbyqxmd.com/read/28727344/-to-where-and-until-when-handle-the-osteoporosis
#8
Brigitte Uebelhart, Serge Ferrari
Estrogen replacement therapy, selective modulators of the estrogen receptor (SERMs), bisphophonates and denosumab are antiresorptive therapies which can be used for several years. Teriparatide is still the only bone forming agent available, its use is limited to 24 months. Except the absence of new fragility fractures, there is no well defined target in the treatment of osteoporosis. Nevertheless persistence of high fracture risk (prevalent fractures and/or low BMD) on therapy indicates to maintain or intensify the treatment...
April 19, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28717268/empiric-medical-therapy-with-hormonal-agents-for-idiopathic-male-infertility
#9
REVIEW
Nicholas N Tadros, Edmund S Sabanegh
INTRODUCTION: Infertility affects approximately 15% of all couples, and male factor contribute to up to 50% of cases. Unfortunately, the cause of male infertility is unknown in about 30% of these cases. Infertility of unknown origin is classified as idiopathic male infertility when abnormal semen parameters are present. Despite not having a definable cause, these men may respond to treatment. This review focuses on the use of empiric hormonal therapies for idiopathic male infertility...
July 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28706360/osteoporosis-prevention-and-management
#10
Muralidhar V Pai
Osteoporosis, defined by BMD at the hip or lumbar spine that is less than or equal to 2.5 standard deviations below the mean BMD of a young-adult reference population, is the most common bone disease in humans affecting both sexes and all races. It's a silent killer affecting the quality of life due to fractures and postural changes. In osteoporosis there is an imbalance between bone formation and bone resorption in favor of latter. Preventive measures and treatments are available to combat this evil. Counseling is the integral part of prevention as well as treatment of osteoporosis...
August 2017: Journal of Obstetrics and Gynaecology of India
https://www.readbyqxmd.com/read/28699698/reduced-dosing-and-liability-in-methadone-maintenance-treatment-by-targeting-oestrogen-signal-for-morphine-addiction
#11
Yao-Chang Chiang, Ruey-Yun Wang, Chieh-Liang Huang, Shue-Hwa Chen, Wen-Jing Ho, Hsien-Yuan Lane, Ing-Kang Ho, Hwei-Ting Yang, Wen-Lung Ma
Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. There have gender differences reported in response to MMT. This study discovered that the estrogen-response element single nucleotide polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone catabolic enzyme) responded differently to MMT dosing. Oestradiol was associated with high MMT dosing, high enantiomer (R- or S-) of 2-ethylidene-1,5-dimethyl-3,3-dipheny-pyrrolidine (EDDP; methadone metabolite) to methadone ratio and increased drug-seeking behaviour, implicating oestradiol-CYP-EDDP/methadone axis decreasing MMT efficacy...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28692232/-osteoporosis-in-menopausal-women-between-40-and-65-years-old-an-algorithm-for-the-gynaecologist
#12
Anna Surbone, Nicolas Vulliemoz, Elena Gonzalez-Rodriguez, Jean-Paul Chatelain, Olivier Lamy
Osteoporosis is a bone disease that promotes the development of fragility fractures. An algorithm is proposed for the gynaecologists'use to diagnose and treat osteoporosis in young menopausal women. The fracture risk can be calculated with the FRAX tool. If the 10-year fracture risk is ≥ 10 %, a bone densitometry is recommended, and the result is integrated in the FRAX tool. If the risk is between 10 and 20 %, a treatment should be discussed individually and, in some cases, a pharmacologic preventive treatment, by menopause hormonal treatment or SERMs, can be initiated...
October 26, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28690107/preventing-invasive-breast-cancer-using-endocrine-therapy
#13
Mangesh A Thorat, Jack Cuzick
Developments in breast cancer treatment have resulted in reduction in breast cancer mortality in the developed world. However incidence continues to rise and greater use of preventive interventions including the use of therapeutic agents is needed to control this burden. High quality evidence from 9 major trials involving more than 83000 participants shows that selective oestrogen receptor modulators (SERMs) reduce breast cancer incidence by 38%. Combined results from 2 large trials with 8424 participants show that aromatase inhibitors (AIs) reduce breast cancer incidence by 53%...
July 6, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28657580/phytochemicals-targeting-estrogen-receptors-beneficial-rather-than-adverse-effects
#14
REVIEW
Sylvain Lecomte, Florence Demay, François Ferrière, Farzad Pakdel
In mammals, the effects of estrogen are mainly mediated by two different estrogen receptors, ERα and ERβ. These proteins are members of the nuclear receptor family, characterized by distinct structural and functional domains, and participate in the regulation of different biological processes, including cell growth, survival and differentiation. The two estrogen receptor (ER) subtypes are generated from two distinct genes and have partially distinct expression patterns. Their activities are modulated differently by a range of natural and synthetic ligands...
June 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28646880/6-shogaol-a-neuroactive-compound-of-ginger-jahe-gajah-induced-neuritogenic-activity-via-ngf-responsive-pathways-in-pc-12-cells
#15
Syntyche Ling Sing Seow, Sok Lai Hong, Guan Serm Lee, Sri Nurestri Abd Malek, Vikineswary Sabaratnam
BACKGROUND: Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jahe gajah (Zingiber officinale var officinale) has shown numerous pharmacological activities, including neuroprotective and anti-neuroinflammatory activities. The aim of this study was to investigate the potential of 6-shogaol to mimic the neuritogenic activity of nerve growth factor (NGF) in rat pheochromocytoma (PC-12) cells...
June 24, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28642035/improving-the-efficacy-of-hormone-therapy-in-breast-cancer-the-role-of-cholesterol-metabolism-in-serm-mediated-autophagy-cell-differentiation-and-death
#16
REVIEW
Julie Leignadier, Florence Dalenc, Marc Poirot, Sandrine Silvente-Poirot
Breast cancer (BC) is one of the most common female cancers in the world, with estrogen receptor (ER)-positive BC the most frequent subtype. Tamoxifen (Tam) is an effective drug that competitively binds to the ER and is routinely used for the treatment of ER-positive BC. However, a number of ER-positive BC do not respond to Tam treatment and acquired resistance is often observed, constituting a major challenge for extending patient life expectancy. The mechanisms responsible for these treatment failures remain unclear, indicating the requirement for other targets and better predictors for patient response to Tam...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28615284/tcl1a-single-nucleotide-polymorphisms-and-estrogen-mediated-toll-like-receptor-myd88-dependent-nuclear-factor-%C3%AE%C2%BAb-activation-single-nucleotide-polymorphism-and-selective-estrogen-receptor-modulator-dependent-modification-of-inflammation-and-immune-response
#17
Ming-Fen Ho, James N Ingle, Tim Bongartz, Krishna R Kalari, Paul E Goss, Lois E Shepherd, Taisei Mushiroda, Michiaki Kubo, Liewei Wang, Richard M Weinshilboum
In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy for breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol, but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the downstream expression of a series of cytokines and chemokines and had a striking effect on nuclear factor κB (NF-κB) transcriptional activity...
August 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28591668/the-selective-estrogen-receptor-modulators-serms-raloxifene-and-tamoxifen-improve-anp-levels-and-decrease-nuclear-translocation-of-nf-kb-in-estrogen-deficient-rats
#18
Aline Z Lamas, Andrews M Nascimento, Ana Raquel S Medeiros, Izabela F Caliman, Polyana L M Dalpiaz, Luciana B Firmes, Glauciene J Sousa, Phablo Wendell C Oliveira, Tadeu U Andrade, Adelina M Reis, Sônia A Gouvea, Nazaré S Bissoli
BACKGROUND: The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported...
March 16, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28583434/27-hydroxycholesterol-a-novel-player-in-molecular-carcinogenesis-of-breast-and-prostate-cancer
#19
REVIEW
Gurdeep Marwarha, Shaneabbas Raza, Kimberly Hammer, Othman Ghribi
Several studies have suggested an etiological role for hypercholesterolemia in the pathogenesis of breast cancer and prostate cancer (PCa). However, the molecular mechanisms that underlie and mediate the hypercholesterolemia-fostered increased risk for breast cancer and PCa are yet to be determined. The discovery that the most abundant cholesterol oxidized metabolite in the plasma, 27 hydroxycholesterol (27-OHC), is a selective estrogen receptor modulator (SERM) and an agonist of Liver X receptors (LXR) partially fills the void in our understanding and knowledge of the mechanisms that may link hypercholesterolemia to development and progression of breast cancer and PCa...
June 2, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28570956/worry-and-risk-perception-of-breast-cancer-in-a-prevention-trial-of-low-dose-tamoxifen-in-midlife-postmenopausal-hormone-users
#20
Gabriella Rondanina, Matteo Puntoni, Aliana Guerrieri-Gonzaga, Domenico Marra, Bernardo Bonanni, Andrea DeCensi
OBJECTIVE: There is increasing interest in combining postmenopausal hormone therapy (HT) and SERMs in midlife women. We previously showed that refusal to participate in a prevention trial of low dose tamoxifen in HT users was associated with higher worry about breast cancer. Given this counterintuitive finding, we studied which factors influenced worry and risk perception of breast cancer. METHODS: We assessed the relationships of breast cancer worry and risk perception with age, age at menopause, Gail risk, education, adherence to mammographic screening, BMI, smoking, physical activity, alcohol use, anxiety and depression in 457 midlife HT users who were eligible to participate in the trial...
May 29, 2017: Breast: Official Journal of the European Society of Mastology
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