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https://www.readbyqxmd.com/read/28827803/host-regulation-of-liver-fibroproliferative-pathology-during-experimental-schistosomiasis-via-interleukin-4-receptor-alpha
#1
Justin Komguep Nono, Hlumani Ndlovu, Nada Abdel Aziz, Thabo Mpotje, Lerato Hlaka, Frank Brombacher
Interleukin-4 receptor (IL-4Rα) is critical for the initiation of type-2 immune responses and implicated in the pathogenesis of experimental schistosomiasis. IL-4Rα mediated type-2 responses are critical for the control of pathology during acute schistosomiasis. However, type-2 responses tightly associate with fibrogranulomatous inflammation that drives host pathology during chronic schistosomiasis. To address such controversy on the role of IL-4Rα, we generated a novel inducible IL-4Rα-deficient mouse model that allows for temporal knockdown of il-4rα gene after oral administration of Tamoxifen...
August 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28827578/low-dose-tamoxifen-treatment-in-juvenile-males-has-long-term-adverse-effects-on-the-reproductive-system-implications-for-inducible-transgenics
#2
Saloni H Patel, Laura O'Hara, Nina Atanassova, Sarah E Smith, Michael K Curley, Diane Rebourcet, Annalucia L Darbey, Anne-Louise Gannon, Richard M Sharpe, Lee B Smith
The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, but >40% of publications that have used tamoxifen to generate conditional knockouts have not reported even the minimum appropriate controls...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819071/genetic-and-non-genetic-factors-associated-with-protein-abundance-of-flavin-containing-monooxygenase-3-in-human-liver
#3
Meijuan Xu, Deepak Kumar Bhatt, Catherine K Yeung, Katrina G Claw, Amarjit S Chaudhry, Andrea Gaedigk, Robin E Pearce, Ulrich Broeckel, Roger Gaedigk, Debbie Nickerson, Erin Schuetz, Allan E Rettie, Steven Leeder, Kenneth E Thummel, Bhagwat Prasad
Hepatic flavin-containing monooxygenase 3 (FMO3) metabolizes a broad array of nucleophilic heteroatom (e.g., N or S)-containing xenobiotics (e.g., amphetamine, sulindac, benzydamine, ranitidine, tamoxifen, nicotine, and ethioniamide), as well as endogenous compounds (e.g., catecholamine and trimethylamine). To predict the effect of genetic and non-genetic factors on the hepatic metabolism of FMO3 substrates, we quantified FMO3 protein abundance in human liver microsomes (HLM; n=445) by LC-MS/MS proteomics. Genotyping/gene-resequencing, mRNA expression, and functional activity (with benzydamine as a probe substrate) of FMO3 were also performed...
August 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#4
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28816986/efficacy-and-safety-of-endocrine-monotherapy-as-first-line-treatment-for-hormone-sensitive-advanced-breast-cancer-a-network-meta-analysis
#5
Jingwen Zhang, Yanhong Huang, Changyi Wang, Yuanfang He, Shukai Zheng, Kusheng Wu
BACKGROUND: Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. METHODS: We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816086/inducible-knockout-of-mouse-zfhx3-emphasizes-its-key-role-in-setting-the-pace-and-amplitude-of-the-adult-circadian-clock
#6
Ashleigh G Wilcox, Lucie Vizor, Michael J Parsons, Gareth Banks, Patrick M Nolan
The transcription factor zinc finger homeobox 3 (ZFHX3) plays a key role in coupling intracellular transcriptional-translational oscillations with intercellular synchrony in mouse suprachiasmatic nucleus (SCN). However, like many key players in central nervous system function, ZFHX3 serves an important role in neurulation and neuronal terminal differentiation while retaining discrete additional functions in the adult SCN. Recently, using a dominant missense mutation in mouse Zfhx3, we established that this gene can modify circadian period and sleep in adult animals...
August 1, 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28814243/a-pharmacokinetic-pharmacodynamic-model-of-tamoxifen-and-endoxifen-to-predict-their-distribution-and-effects-on-inhibition-of-tumor-growth
#7
Shengyue Yuan, Qingrong Sun, Yao Chen, Jun Liao
BACKGROUND: Tamoxifen is widely used in the therapy for breast cancer and has three major metabolites, N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen. Endoxifen has played a major role in the inhibition of tumor growth of breast cancer and the tumor growth is related to endoxifen concentration. OBJECTIVES: The aim of this study was to develop a pharmacokinetic-pharmacodynamic model to predict the distribution of tamoxifen and endoxifen quantitatively, and to discover the anti-tumor effect patterns of tamoxifen and endoxifen...
August 15, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28812763/enhancing-the-solubility-and-bioactivity-of-anticancer-drug-tamoxifen-by-water-soluble-pillar-6-arene-based-host-guest-complexation
#8
Liqing Shangguan, Qi Chen, Bingbing Shi, Feihe Huang
A water-soluble pillar[6]arene functions as a solubilizing agent to enhance the solubility and bioactivity of poorly water-soluble anticancer drug tamoxifen by host-guest complexation between it and tamoxifen.
August 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28811827/pharmacodynamics-and-medicinal-chemistry-of-an-external-chinese-herbal-formula-for-mammary-precancerous-lesions
#9
Ruixue Chen, Guijuan Zhang, Yi Ma, Fengjie Bie, Hongxia Fan, Min Ma
Ruyan Neixiao Cream (RYNXC) is a traditional Chinese herbal formula for treating mammary precancerous disease. This study was carried out to investigate in vivo anticancer effect of RYNXC and multiple constituents. 32 virginal Sprague-Dawley rats were randomly divided into blank control group (BC), mammary precancer models group (MODEL), tamoxifen group (TAM), and Ruyan Neixiao Cream group (RYNXC). TAM was intervened by tamoxifen; RYNXC was intervened by Ruyan Neixiao Cream. The chromatographic separation was performed by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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
#10
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/28806084/photochemical-activation-of-tertiary-amines-for-applications-in-studying-cell-physiology
#11
Naeem Asad, Davide Deodato, Xin Lan, Magnus B Widegren, David Lee Phillips, Lili Du, Timothy M Dore
Representative tertiary amines were linked to the 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group (PPG) to create photoactivatable forms suitable for use in studying cell physiology. The photoactivation of tamoxifen and 4-hydroxytamoxifen, which can be used to activate Cre recombinase and CRISPR-Cas9 gene editing, demonstrated that highly efficient release of bioactive molecules could be achieved through 1- and 2-photon excitation (1PE and 2PE). CyHQ-protected anilines underwent a photo-aza-Claisen rearrangement instead of releasing amines...
August 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28802897/the-different-effects-of-lithium-and-tamoxifen-on-memory-formation-and-the-levels-of-neurotrophic-factors-in-the-brain-of-male-and-female-rats
#12
Samira S Valvassori, Cenita Borges, Roger B Varela, Daniela V Bavaresco, Guilherme Bianchini, Edemilson Mariot, Camila O Arent, Wilson R Resende, Josiane Budni, João Quevedo
Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28 days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition)...
August 9, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28802188/risk-of-uterine-cancer-for-brca1-and-brca2-mutation-carriers
#13
Y C Lee, R L Milne, S Lheureux, M Friedlander, S A McLachlan, K L Martin, M Q Bernardini, C Smith, S Picken, S Nesci, J L Hopper, K A Phillips
BACKGROUND: Whether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery. AIM: This multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population. METHODS: Eligible mutation carriers were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) cohort study, had a uterus present and no history of uterine cancer at cohort entry...
August 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28799536/estrogen-receptor-esr1-mutation-in-bone-metastases-from-breast-cancer
#14
Stephan Bartels, Matthias Christgen, Angelina Luft, Sascha Persing, Kai Jödecke, Ulrich Lehmann, Hans Kreipe
Activating mutations of estrogen receptor α gene (ESR1) in breast cancer can cause endocrine resistance of metastatic tumor cells. The skeleton belongs to the metastatic sides frequently affected by breast cancer. The prevalence of ESR1 mutation in bone metastasis and the corresponding phenotype are not known. In this study bone metastases from breast cancer (n=231) were analyzed for ESR1 mutation. In 27 patients (12%) (median age 73 years, range: 55-82 years) activating mutations of ESR1 were detected. The most frequent mutation was p...
August 11, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28798474/cyp2c19-2-and-cyp2c19-17-variants-and-effect-of-tamoxifen-on-breast-cancer-recurrence-analysis-of-the-international-tamoxifen-pharmacogenomics-consortium-dataset
#15
Per Damkier, Anders Kjærsgaard, Kimberly A Barker, Deidre Cronin-Fenton, Anatasha Crawford, Ylva Hellberg, Emilius A M Janssen, Carl Langefeld, Thomas P Ahern, Timothy L Lash
The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#16
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28782393/chemical-composition-and-cytotoxic-activity-of-garcinia-atroviridis-griff-ex-t-anders-essential-oils-in-combination-with-tamoxifen
#17
Wen-Nee Tan, Jia-Qin Lim, Fatin Afiqah, Nik Nur Syazni Nik Mohamed Kamal, Fatin Athirah Abdul Aziz, Woei-Yenn Tong, Chean-Ring Leong, Jun-Wei Lim
Garcinia atroviridis Griff. ex T. Anders. is used as a medication agent in folkloric medicine. The present study was to examine the chemical composition of the stem bark and leaf of G. atroviridis as well as their cytotoxic effects against MCF-7 cells. The constituents obtained by hydrodistillation were identified using GC-MS. The stem bark oil (EO-SB) composed mainly the palmitoleic acid (51.9%) and palmitic acid (21.9%), while the leaf oil (EO-L) was dominated by (E)-β-farnesene (58.5%) and β-caryophyllene (16...
August 7, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28776283/tamoxifen-therapy-benefit-for-patients-with-70-gene-signature-high-and-low-risk
#18
Laura J van 't Veer, Christina Yau, Nancy Y Yu, Christopher C Benz, Bo Nordenskjöld, Tommy Fornander, Olle Stål, Laura J Esserman, Linda Sofie Lindström
BACKGROUND: Breast cancer molecular prognostic tools that predict recurrence risk have mainly been established on endocrine-treated patients and thus are not optimal for the evaluation of benefit from endocrine therapy. The Stockholm tamoxifen (STO-3) trial which randomized postmenopausal node-negative patients to 2-year tamoxifen (followed by an optional randomization for an additional 3-year tamoxifen vs nil), versus no adjuvant treatment, provides a unique opportunity to evaluate long-term 20-year benefit of endocrine therapy within prognostic risk classes of the 70-gene prognosis signature that was developed on adjuvantly untreated patients...
August 4, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28775043/oestrogen-inhibition-reverses-pulmonary-arterial-hypertension-and-associated-metabolic-defects
#19
Xinping Chen, Eric D Austin, Megha Talati, Joshua P Fessel, Eric H Farber-Eger, Evan L Brittain, Anna R Hemnes, James E Loyd, James West
Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice.The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28768570/primary-cytoreductive-surgery-and-adjuvant-hormonal-monotherapy-in-women-with-advanced-low-grade-serous-ovarian-carcinoma-reducing-overtreatment-without-compromising-survival
#20
Amanda N Fader, Jennifer Bergstrom, Amelia Jernigan, Edward J Tanner, Kara Long Roche, Rebecca L Stone, Kimberly L Levinson, Stephanie Ricci, Stephanie Wethingon, Tian-Li Wang, Ie-Ming Shih, Bin Yang, Gloria Zhang, Deborah K Armstrong, Stephanie Gaillard, Chad Michener, Robert DeBernardo, Peter G Rose
OBJECTIVES: Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). METHODS: A retrospective study was performed at two academic cancer centers...
July 30, 2017: Gynecologic Oncology
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