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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/28091621/differential-susceptibility-and-maturation-of-thymocyte-subsets-during-salmonella-typhimurium-infection-insights-on-the-roles-of-glucocorticoids-and-interferon-gamma
#1
Shamik Majumdar, Mukta Deobagkar-Lele, Vasista Adiga, Abinaya Raghavan, Nitin Wadhwa, Syed Moiz Ahmed, Supriya Rajendra Rananaware, Subhashish Chakraborty, Omana Joy, Dipankar Nandi
The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4(-)CD8(-) double negative (DN) thymocytes is observed. Second, CD4(+)CD8(+) double positive (DP) thymocytes, mainly in the DP1 (CD5(lo)CD3(lo)) and DP2 (CD5(hi)CD3(int)), but not DP3 (CD5(int)CD3(hi)), subsets are reduced...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#2
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28068412/a-comparison-of-gene-expression-profiles-between-glucocorticoid-responder-and-non-responder-bovine-trabecular-meshwork-cells-using-rna-sequencing
#3
Jaclyn Y Bermudez, Hannah C Webber, Bartley Brown, Terry A Braun, Abbot F Clark, Weiming Mao
The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain...
2017: PloS One
https://www.readbyqxmd.com/read/28061324/oral-corticosterone-administration-reduces-insulitis-but-promotes-insulin-resistance-and-hyperglycemia-in-male-nonobese-diabetic-mice
#4
Susan J Burke, Heidi M Batdorf, Adrianna E Eder, Michael D Karlstad, David H Burk, Robert C Noland, Z Elizabeth Floyd, J Jason Collier
Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic...
January 4, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28046097/glucocorticoid-insensitivity-in-virally-infected-airway-epithelial-cells-is-dependent-on-transforming-growth-factor-%C3%AE-activity
#5
Yuxiu C Xia, Asmaa Radwan, Christine R Keenan, Shenna Y Langenbach, Meina Li, Danica Radojicic, Sarah L Londrigan, Rosa C Gualano, Alastair G Stewart
Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28045461/antidepressant-responsiveness-in-adulthood-is-permanently-impaired-after-neonatal-destruction-of-the-neurogenic-pool
#6
S Yu, I Zutshi, R Stoffel, J Zhang, A P Ventura-Silva, N Sousa, P S Costa, F Holsboer, A Patchev, O F X Almeida
The dynamic turnover of hippocampal neurons is implicated in the regulation of cognitive and affective behavior. Extending our previous demonstration that administration of dexamethasone (ND) to neonatal rats depletes the resident population of neural precursor cells (NPC) and restrains the size of the neurogenic regions, we now show that the adverse effects of ND persist into adulthood. Specifically, ND impairs repletion of the neurogenic pool and neurogenesis; ND also compromises cognitive performance, the ability to actively adapt to an acute stressor and, the efficacy of glucocorticoid (GC) negative feedback...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28036309/rapid-transmission-of-multidrug-resistant-corynebacterium-striatum-among-susceptible-patients-in-a-tertiary-hospital-in-china
#7
Junrui Wang, Yanyan Wang, Xiaoli Du, Jinghua Cui, Kai Wang, Lipeng Zhang, Yanqiu Han
INTRODUCTION: With increasing reports about Corynebacterium striatum, its potential pathogenicity and clinical significance are drawing more attention in recent years. METHODOLOGY: During a 14-month period, Corynebacterium striatum strains were routinely isolated in lower respiratory tract samples of the inpatients in a tertiary hospital in China, and the suspected isolates were identified with VITEK-2 ANC card and 16S rRNA sequencing technique, respectively. Pulsed-field gel electrophoresis (PFGE) was employed to discriminate different clones, and biofilm-producing abilities of different strains were compared...
December 30, 2016: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/28035377/histone-deacetylases-meet-microrna-associated-mmp-9-expression-regulation-in-glucocorticoid-sensitive-and-resistant-cell-lines
#8
Marwa Hentati-Kallel, Sébastien Le Jan, Philippe Bernard, Frank Antonicelli, Aurélie Trussardi-Régnier
Glucocorticoids are largely used in the treatment of inflammatory pathologies and/or hematological malignancies and regulate the expression of a variety of genes involved in inflammation or metastasis such as matrix metalloproteinases (MMP). Long-term exposure to glucocorticoids can result in failure of responsiveness, which is often associated with an unwanted gene expression. Epigenetic mechanisms are involved in gene expression modulated after development of glucocorticoid resistance but how these mechanisms take place must be further studied...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28035367/redistribution-of-adrenomedullary-nicotinic-acetylcholine-receptor-subunits-and-the-effect-on-circulating-epinephrine-levels-in-a-murine-model-of-acute-asthma
#9
Xi Chen, Juntao Feng, Chengping Hu, Qingwu Qin, Yuanyuan Li, Ling Qin
The lack of circulating epinephrine (EPI) in the pathogenesis of asthma has long been attributed to the lack of adrenergic nerves in human airways. However, in this study we considered that EPI levels are regulated by EPI release in addition to synthesis. Nicotinic acetylcholine receptors (nAChRs) have been shown to control EPI release, and we hypothesized that redistribution of nAChR subunits modulates EPI release and circulating EPI levels. Using a mouse model of asthma, circulating EPI levels were measured by enzyme-linked immunosorbent assays...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28030791/dexamethasone-induces-docetaxel-and-cisplatin-resistance-partially-through-up-regulating-kr%C3%A3-ppel-like-factor-5-in-triple-negative-breast-cancer
#10
Zhen Li, Jian Dong, Tianning Zou, Chengzhi Du, Siyuan Li, Ceshi Chen, Rong Liu, Kunhua Wang
PURPOSE: Dexamethasone (Dex), a glucocorticoid (GC), is used as a pretreatment drug in cancer patients undergoing chemotherapy. Dex functions by binding to the glucocorticoid receptor (GR) to prevent allergic reactions and severe chemotherapeutic side effects such as nausea and vomiting. However, the mechanisms by which Dex causes chemoresistance remain unknown. METHODS: We used docetaxel and cisplatin to treat triple-negative breast cancer (TNBC) cells with or without Dex and assessed cell proliferation using a sulforhodamine B colorimetric (SRB) assay...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28007534/fkbp5-polymorphism-is-associated-with-insulin-resistance-in-children-and-adolescents-with-obesity
#11
Marta Fichna, Izabela Krzyśko-Pieczka, Magdalena Żurawek, Bogda Skowrońska, Danuta Januszkiewicz-Lewandowska, Piotr Fichna
OBJECTIVE: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis...
December 19, 2016: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/27999674/development-and-validation-of-a-novel-bioassay-to-determine-glucocorticoid-sensitivity
#12
Emily L Williams, Madeleine L Stimpson, Peter L Collins, Doyo G Enki, Ashish Sinha, Richard W Lee, Ashwin D Dhanda
BACKGROUND: Glucocorticoids (GCs) remain the first line treatment for almost all non-infectious inflammatory diseases, ranging from acute asthma to rheumatoid arthritis. However, across all conditions, patients have a variable response to GCs with approximately 30% being non-responders. This group of GC resistant patients is typically exposed to high-dose GCs and their side-effects before more appropriate immunotherapy is instituted. Hence, there is a pressing clinical need for a predictive biomarker of GC responsiveness...
2016: Biomarker Research
https://www.readbyqxmd.com/read/27998642/bone-histomorphometry-in-de-novo-renal-transplant-recipients-indicates-a-further-decline-in%C3%A2-bone-resorption-1-year-posttransplantation
#13
Pieter Evenepoel, Geert J Behets, Liesbeth Viaene, Patrick C D'Haese
Renal transplantation is believed to have a major impact on bone health. The present prospective observational bone biopsy study aimed to define the natural history of bone histomorphometry parameters in contemporaneous de novo renal transplant recipients. Paired bone biopsies were performed at the time of transplantation and at one-year posttransplantation in an unselected cohort of 36 patients referred for deceased kidney replacement. Parameters of mineral metabolism and circulating bone turnover markers were monitored as well...
December 17, 2016: Kidney International
https://www.readbyqxmd.com/read/27997270/molecular-interactions-of-dioxins-and-dlcs-with-the-ketosteroid-receptors-an-in-silico-risk-assessment-approach
#14
Mohemmed Faraz Khan, M Mumtaz Alam, Garima Verma, Wasim Akhtar, Moshahid A Rizvi, Asif Ali, Mymoona Akhter, M Shaquiquzzaman
Dioxins and dioxin like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects...
December 20, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27993966/characterization-of-an-abiraterone-ultraresponsive-phenotype-in-castration-resistant-prostate-cancer-patient-derived-xenografts
#15
Hung-Ming Lam, Ryan McMullin, Holly Nguyen, Ilsa Coleman, Michael Gormley, Roman Gulati, Lisha Brown, Sarah Holt, Weimin Li, Deborah S Ricci, Karin Verstraeten, Shibu Thomas, Elahe A Mostaghel, Peter S Nelson, Robert Vessella, Eva Corey
PURPOSE: To identify the molecular signature associated with abiraterone acetate (AA) response and mechanisms underlying AA resistance in castration-resistant prostate cancer patient-derived xenografts (PDXs). EXPERIMENTAL DESIGN: SCID mice bearing LuCaP 136CR, 77CR, 96CR, and 35CR PDXs were treated with AA. Tumor volume and prostate-specific antigen were monitored, and tumors were harvested 7 days post-treatment or at end of study for gene expression and immunohistochemical studies...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27987128/the-role-of-glucocorticoid-receptor-in-prostate-cancer-progression-from-bench-to-bedside
#16
REVIEW
Jieping Hu, Qingke Chen
Glucocorticoids are a common class of adjuvant drugs for the treatment of castration-resistant prostate cancer (CRPC) combined with antitumour or antiandrogen agents. Glucocorticoids are administered clinically because they ameliorate toxic side effects and have inhibitory effects on adrenal androgen production, acting as a pituitary suppressant. However, their effects on prostate cancer cells especially the castration resistance prostate cancer cells are poorly defined. Glucocorticoids exert effects depend to a great extent on glucocorticoid receptor...
December 16, 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27982079/ginsenoside-rg1-attenuates-ultraviolet-b-induced-glucocortisides-resistance-in-keratinocytes-via-nrf2-hdac2-signalling
#17
Jun Li, Dong Liu, Jinfeng Wu, Daniel Zhang, Binbin Cheng, Yani Zhang, Zifei Yin, Yuan Wang, Juan Du, Changquan Ling
Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells)...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27980230/a-childhood-acute-lymphoblastic-leukemia-specific-lncrna-implicated-in-prednisolone-resistance-cell-proliferation-and-migration
#18
Manon Ouimet, Simon Drouin, Mathieu Lajoie, Maxime Caron, Pascal St-Onge, Romain Gioia, Chantal Richer, Daniel Sinnett
Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer and, despite an 85% cure rate, still represents a major cause of disease-related death in children. Recent studies have implicated long non-coding RNAs (lncRNAs) in cALL etiology, progression, and treatment response. However, barring some exceptions little is known about the functional impact of lncRNAs on cancer biology, which limits their potential as potential therapeutic targets. We wanted to investigate the functional role of lncRNAs identified as specifically overexpressed in pre-B cALL by whole-transcriptome sequencing...
December 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27979924/tumor-suppressors-btg1-and-ikzf1-cooperate-during-mouse-leukemia-development-and-increase-relapse-risk-in-b-cell-precursor-acute-lymphoblastic-leukemia-patients
#19
Blanca Scheijen, Judith M Boer, Rene' Marke, Esther Tijchon, Dorette van Ingen Schenau, Esme' Waanders, Liesbeth van Emst, Laurens T van der Meer, Rob Pieters, Gabriele Escherich, Martin A Horstmann, Edwin Sonneveld, Nicola Venn, Rosemary Sutton, Luciano Dalla-Pozza, Roland P Kuiper, Peter M Hoogerbrugge, Monique L den Boer, Frank N van Leeuwen
Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single copy losses of BTG1 were significantly enriched in IKZF1-deleted B-cell precursor acute lymphoblastic leukemia (P=0...
December 15, 2016: Haematologica
https://www.readbyqxmd.com/read/27960157/chorein-sensitive-orai1-expression-and-store-operated-ca2-entry-in-rhabdomyosarcoma-cells
#20
Willi Yu, Sabina Honisch, Sebastian Schmidt, Jing Yan, Evi Schmid, Saad Alkahtani, Abdullah A AlKahtane, Saud Alarifi, Christos Stournaras, Florian Lang
BACKGROUND: Chorein, a protein encoded by VPS13A (vacuolar protein sorting-associated protein 13A), is defective in chorea acanthocytosis, a rare disease characterized by acanthocytosis of red blood cells and neuronal cell death with progressive hyperkinetic movement disorder, cognitive dysfunction, behavioral abnormalities and chronic hyperkalemia. Chorein is highly expressed in ZF rhabdomyosarcoma cells and counteracts apoptosis of those cells. Chorein is effective in part by interacting with and fostering stimulation of phosphoinositide-3-kinase (PI3K)-p85-subunit...
2016: Cellular Physiology and Biochemistry
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