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Tamoxifen

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https://www.readbyqxmd.com/read/28526959/adjuvant-tamoxifen-but-not-aromatase-inhibitor-therapy-decreases-serum-levels-of-the-wnt-inhibitor-dickkopf-1-while-not-affecting-sclerostin-in-breast-cancer-patients
#1
Andy Göbel, Jan D Kuhlmann, Theresa Link, Pauline Wimberger, Andrew J Browne, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner
PURPOSE: Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive...
May 19, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28522855/phosphoserine-aminotransferase-1-is-associated-to-poor-outcome-on-tamoxifen-therapy-in-recurrent-breast-cancer
#2
Tommaso De Marchi, Mieke A Timmermans, Anieta M Sieuwerts, Marcel Smid, Maxime P Look, Nicolai Grebenchtchikov, Fred C G J Sweep, Jan G Smits, Viktor Magdolen, Carolien H M van Deurzen, John A Foekens, Arzu Umar, John W Martens
In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient's time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521859/-evaluation-of-primary-adherence-to-medications-in-patients-with-chronic-conditions-a-retrospective-cohort-study
#3
Francisco Emiliano Peper, Santiago Esteban, Sergio Adrian Terrasa
OBJECTIVES: To assess the proportion of members of a private health insurance at the Hospital Italiano de Buenos Aires with primary adherence to, 1) bisphosphonates for secondary prevention of osteoporotic fractures, 2) insulin and metformin in type 2 diabetes, and 3) tamoxifen in the context of treatment of breast cancer. DESIGN: Retrospective cohort study to determine the proportion of primary treatment adherence during 2012 and 2013. SITE: Hospital Italiano de Buenos Aires, Argentina...
May 15, 2017: Atencion Primaria
https://www.readbyqxmd.com/read/28521362/association-of-common-genetic-variants-with-contralateral-breast-cancer-risk-in-the-wecare-study
#4
Mark E Robson, Anne S Reiner, Jennifer D Brooks, Patrick J Concannon, Esther M John, Lene Mellemkjaer, Leslie Bernstein, Kathleen E Malone, Julia A Knight, Charles F Lynch, Meghan Woods, Xiaolin Liang, Robert W Haile, David J Duggan, Roy E Shore, Susan A Smith, Duncan C Thomas, Daniel O Stram, Jonine L Bernstein
Background: Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown. Methods: Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28515111/racial%C3%A2-differences-in-adjuvant-endocrine-therapy-use-and-discontinuation-in-association-with-mortality-among-medicare-breast-cancer-patients-by-receptor-status
#5
Albert J Farias, Xianglin L Du
BACKGROUND: There are racial disparities in breast cancer mortality. Our purpose was to determine whether racial/ethnic differences in use and discontinuation of AET differed by hormone receptor status and whether discontinuation was associated with mortality. METHODS: We conducted a retrospective cohort study with SEER/Medicare dataset of women age 65 years or older diagnosed with stage I-III breast cancer in Medicare Part-D from 2007-2009, stratified by hormone receptor status...
May 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28511462/story-of-a-giant-endometrial-polyp-in-asymptomatic-postmenopausal-female
#6
Jahnavi Meena, Rahul Manchanda, Sudhir Kulkarni, Nirmal Bhargava, Priyanka Mahawar
Endometrial polyps are localized overgrowth of endometrial glands and stoma through the uterine cavity. They are associated with postmenopausal bleeding, infertility and menorrhagia and are affected by unbalanced oestrogen therapy or increased frequency of tamoxifen exposure. We report a case of giant endometrial polyp in postmenopausal female without vaginal bleeding and hormone or drug use. A 65-year-old, postmenopausal female P3L2 with hypertension and Diabetes Mellitus (DM) came for routine health check-up...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507152/embryonic-transcription-factor-sox9-drives-breast-cancer-endocrine-resistance
#7
Rinath Jeselsohn, MacIntosh Cornwell, Matthew Pun, Gilles Buchwalter, Mai Nguyen, Clyde Bango, Ying Huang, Yanan Kuang, Cloud Paweletz, Xiaoyong Fu, Agostina Nardone, Carmine De Angelis, Simone Detre, Andrew Dodson, Hisham Mohammed, Jason S Carroll, Michaela Bowden, Prakash Rao, Henry W Long, Fugen Li, Mitchell Dowsett, Rachel Schiff, Myles Brown
The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28506582/dual-functional-small-molecule-fluorescent-probes-for-image-guided-estrogen-receptor-specific-targeting-coupled-potent-antiproliferative-potency-for-breast-cancer-therapy
#8
Lu Yang, Zhiye Hu, Junjie Luo, Chu Tang, Silong Zhang, Wentao Ning, Chune Dong, Jian Huang, Xianjun Liu, Hai-Bing Zhou
A strategy by integrating biological imaging into early stages of the drug discovery process can improve our understanding of drug activity during preclinical and clinical study. In this article, we designed and synthesized coumarin-based nonsteroidal type fluorescence ligands for drug-target binding imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER binding affinity and 3e (IC50=0.012μM) exhibited excellent ERα antagonistic activity, its antiproliferative potency in breast cancer MCF-7 cells is equipotent to the approved drug tamoxifen...
May 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28505536/design-synthesis-molecular-docking-and-cytotoxic-evaluation-of-novel-2-furybenzimidazoles-as-vegfr-2-inhibitors
#9
Mona A Abdullaziz, Heba T Abdel-Mohsen, Ahmed M El Kerdawy, Fatma A F Ragab, Mamdouh M Ali, Sherifa M Abu-Bakr, Adel S Girgis, Hoda I El Diwani
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21...
April 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28504114/a-shortened-tamoxifen-induction-scheme-to-induce-creer-recombinase-without-side-effects-on-the-male-mouse-skeleton
#10
Ferran Jardí, Michaël R Laurent, Vanessa Dubois, Rougin Khalil, Ludo Deboel, Dieter Schollaert, Ludo Van Den Bosch, Brigitte Decallonne, Geert Carmeliet, Frank Claessens, Dirk Vanderschueren
The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or antagonistic actions on several tissues, including bone. The off-target effects of tamoxifen are one of the most widely recognized pitfalls of tamoxifen-inducible Cre recombinases (CreERs), potentially confounding the phenotypic findings. Still, the validation of tamoxifen induction schemes that minimize the side effects of the drug has not been addressed. Here, we compared the side effects on the skeleton and other androgen-responsive targets of a shortened tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard protocol (4 doses) and determined their efficiency in inducing CreER-mediated gene deletion...
May 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28503414/adult-onset-deletion-of-the-prader-willi-syndrome-susceptibility-gene-snord116-in-mice-results-in-reduced-feeding-and-increased-fat-mass
#11
Louise Purtell, Yue Qi, Lesley Campbell, Amanda Sainsbury, Herbert Herzog
BACKGROUND: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in the aetiology of Prader-Willi syndrome (PWS), a disease associated with hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to lead to increased food intake but not to the development of obesity. To determine the role of Snord116 independent of potential compensatory developmental factors, we investigated the effects of conditional adult-onset deletion of Snord116 in mice. METHODS: Deletion of Snord116 was induced at 8 weeks of age by oral administration of tamoxifen to male Snord(lox/lox); ROSA(cre/+) mice, with vehicle-treated mice used as controls...
April 2017: Translational pediatrics
https://www.readbyqxmd.com/read/28502695/selective-activation-of-estrogen-receptor-%C3%AE-activation-function-1-is-sufficient-to-prevent-obesity-steatosis-and-insulin-resistance-in-mouse
#12
Maeva Guillaume, Sandra Handgraaf, Aurélie Fabre, Isabelle Raymond-Letron, Elodie Riant, Alexandra Montagner, Alexia Vinel, Melissa Buscato, Natalia Smirnova, Coralie Fontaine, Hervé Guillou, Jean-François Arnal, Pierre Gourdy
Estrogen receptor α (ERα) regulates gene transcription through two activation functions (ERα-AF1 and ERα-AF2). We recently found that the protection conferred by 17β-estradiol against obesity and insulin resistance requires ERα-AF2 but not ERα-AF1. However, the interplay between the two ERα-AFs is poorly understood in vivo and the metabolic influence of a specific ERα-AF1 action remains to be explored. To this end, wild-type, ERα-deficient, or ERα-AF1-deficient ovariectomized female mice were fed a high-fat diet and concomitantly administered with vehicle or tamoxifen, a selective ER modulator that acts as a ERα-AF1 agonist/ERα-AF2 antagonist...
May 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28500839/evaluating-the-efficacy-of-post-surgery-adjuvant-therapies-used-for-ductal-carcinoma-in-situ-patients-a-network-meta-analysis
#13
Li Wang, Yaoxiong Xia, Dequan Liu, Yueqin Zeng, Li Chang, Lan Li, Yu Hou, Lv Ge, Wenhui Li, Zhijie Liu
OBJECTIVE: Post-surgery adjuvant therapies are very important for patients suffering from ductal carcinoma in situ (DCIS). In this study we conducted a network meta-analysis (NMA) to evaluate the efficacy of different post-surgery adjuvant therapies including tamoxifen, anastrozole and radiation therapy (RT) and their combinations (RT+ tamoxifen and RT+ anastrozole). METHODS: We searched several databases, including Embase, MEDLINE / PUBMED, Cochrane Library, and Science Citation Index, for relevant studies...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28500323/development-of-an-inducible-mouse-model-of-irfp713-to-track-recombinase-activity-and-tumour-development-in-vivo
#14
Andreas K Hock, Eric C Cheung, Timothy J Humpton, Tiziana Monteverde, Viola Paulus-Hock, Pearl Lee, Ewan McGhee, Alessandro Scopelliti, Daniel J Murphy, Douglas Strathdee, Karen Blyth, Karen H Vousden
While the use of bioluminescent proteins for molecular imaging is a powerful technology to further our understanding of complex processes, fluorescent labeling with visible light fluorescent proteins such as GFP and RFP suffers from poor tissue penetration and high background autofluorescence. To overcome these limitations, we generated an inducible knock-in mouse model of iRFP713. This model was used to assess Cre activity in a Rosa Cre-ER background and quantify Cre activity upon different tamoxifen treatments in several organs...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500289/stapled-big3-helical-peptide-erap-potentiates-anti-tumour-activity-for-breast-cancer-therapeutics
#15
Tetsuro Yoshimaru, Keisuke Aihara, Masato Komatsu, Yosuke Matsushita, Yasumasa Okazaki, Shinya Toyokuni, Junko Honda, Mitsunori Sasa, Yasuo Miyoshi, Akira Otaka, Toyomasa Katagiri
Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500244/tamoxifen-reduces-hepatic-vldl-production-and-gh-secretion-in-women-a-possible-mechanism-for-steatosis-development
#16
Vita Birzniece, P Hugh R Barrett, Ken K Y Ho
CONTEXT: Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. AIM: To investigate whether tamoxifen reduces hepatic VLDL secretion. DESIGN: Eight healthy, normolipidemic women (age 64...
May 12, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28498888/cardiomyocyte-specific-loss-of-mitochondrial-p32-c1qbp-causes-cardiomyopathy-and-activates-stress-responses
#17
Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima, Dongchon Kang
Aims: Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. The goal of this study was to examine the physiological function of mitochondrial p32/C1qbp in the heart...
May 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28498717/melatonin-as-a-versatile-molecule-to-design-novel-multitarget-hybrids-against-neurodegeneration
#18
Eva Ramos, Javier Egea, Cristóbal de Los Ríos, José Marco-Contelles, Alejandro Romero
Melatonin is an indoleamine produced mainly in the pineal gland. The natural decline of melatonin levels with aging strongly contributes to the development of neurodegenerative disorders. Pleiotropic actions displayed by melatonin prevent several processes involved in neurodegeneration such as neuroinflammation, oxidative stress, excitotoxicity and/or apoptosis. This review focuses on a number of melatonin hybrids resulting from the juxtaposition of tacrine, berberine, tamoxifen, curcumin, N,N-dibenzyl(N-methyl)amine, among others, with potential therapeutic effects for the treatment of neurodegenerative diseases...
May 12, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28498399/dual-inhibition-of-igf1r-and-er-enhances-response-to-trastuzumab-in-her2-positive-breast-cancer-cells
#19
Martina S J McDermott, Alexandra Canonici, Laura Ivers, Brigid C Browne, Stephen F Madden, Neil A O'Brien, John Crown, Norma O'Donovan
Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive...
April 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497301/various-regulatory-modes-for-circadian-rhythmicity-and-sexual-dimorphism-in-the-non-neuronal-cardiac-cholinergic-system
#20
Shino Oikawa, Yuko Kai, Asuka Mano, Hisayuki Ohata, Takahiro Nemoto, Yoshihiko Kakinuma
Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern...
May 11, 2017: Journal of Cardiovascular Translational Research
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