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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/27903230/glucocorticoid-receptor-interacting-co-regulators-putative-candidates-for-future-drug-targeting-therapy
#1
Alessia Di Silvestre, Marianna Lucafò, Sara De Iudicibus, Alessandro Ventura, Stefano Martelossi, Gabriele Stocco, Giuliana Decorti
Glucocorticoids (GCs) are largely used in different inflammatory, autoimmune and proliferative diseases. To date their mechanism of action is not completely clear and more studies are necessary, in particular to explain the great interindividual variability in clinical response. In this panorama the glucocorticoid receptor (GR) has an important role: in fact it regulates the pharmacological response thanks to the capability to interact with different molecules (DNA, RNA, ncRNA and proteins) that are known to influence its activity...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27903154/type-2-diabetes-mellitus-and-cancer-the-role-of-pharmacotherapy
#2
Gadi Shlomai, Brian Neel, Derek LeRoith, Emily Jane Gallagher
Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27896363/oxygen-ultra-fine-bubbles-water-administration-prevents-bone-loss-of-glucocorticoid-induced-osteoporosis-in-mice-by-suppressing-osteoclast-differentiation
#3
T Noguchi, K Ebina, M Hirao, T Morimoto, K Koizumi, K Kitaguchi, H Matsuoka, T Iwahashi, H Yoshikawa
: Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro. INTRODUCTION: Ultra-fine bubbles (<200 nm in diameter) have several unique properties, and they are tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on glucocorticoid-induced osteoporosis (GIO) model mice...
November 28, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#4
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#5
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumour suppressors and oncogenes. In mouse models the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the 'sphingolipid rheostat' from ceramide to sphingosine-1-phosphate (S1P)...
November 21, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27861636/association-between-higher-serum-cortisol-levels-and-decreased-insulin-secretion-in-a-general-population
#6
Aya Kamba, Makoto Daimon, Hiroshi Murakami, Hideyuki Otaka, Kota Matsuki, Eri Sato, Jutaro Tanabe, Shinobu Takayasu, Yuki Matsuhashi, Miyuki Yanagimachi, Ken Terui, Kazunori Kageyama, Itoyo Tokuda, Ippei Takahashi, Shigeyuki Nakaji
Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study...
2016: PloS One
https://www.readbyqxmd.com/read/27858284/role-of-cannabinoid-receptor-1-in-human-adipose-tissue-for-lipolysis-regulation-and-insulin-resistance
#7
Cherno O Sidibeh, Maria J Pereira, Joey Lau Börjesson, Prasad G Kamble, Stanko Skrtic, Petros Katsogiannos, Magnus Sundbom, Maria K Svensson, Jan W Eriksson
We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed...
November 17, 2016: Endocrine
https://www.readbyqxmd.com/read/27856655/glucocorticoids-and-chronic-inflammation
#8
REVIEW
Rainer H Straub, Maurizio Cutolo
Glucocorticoids are steroid hormones that once bound to their receptor interact with the DNA binding domain. Almost 1000-2000 genes are sensitive to their effects, including immune/inflammatory response genes. However, their role in pathophysiology and therapy is still debated. We performed a literature survey using the key words glucocorticoids, inflammation, autoimmune disease, rheumatology and adrenal glands in order to define important targets for this review on glucocorticoids. Considering endogenous/exogenous glucocorticoids in chronic inflammatory diseases brought up five major points for discussion: inadequately low production of endogenous cortisol relative to systemic inflammation (the disproportion principle); changes of the systemic and local cortisol-to-cortisone shuttle (reactivation and degradation of cortisol); inflammation-induced glucocorticoid resistance; highlights of present glucocorticoid therapy; and the role of circadian rhythms in action of cortisol...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#9
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27849045/deletion-of-neurotrophin-signaling-through-the-glucocorticoid-receptor-pathway-causes-tau-neuropathology
#10
Margarita Arango-Lievano, Camille Peguet, Matthias Catteau, Marie-Laure Parmentier, Synphen Wu, Moses V Chao, Stephen D Ginsberg, Freddy Jeanneteau
Glucocorticoid resistance is a risk factor for Alzheimer's disease (AD). Molecular and cellular mechanisms of glucocorticoid resistance in the brain have remained unknown and are potential therapeutic targets. Phosphorylation of glucocorticoid receptors (GR) by brain-derived neurotrophic factor (BDNF) signaling integrates both pathways for remodeling synaptic structure and plasticity. The goal of this study is to test the role of the BDNF-dependent pathway on glucocorticoid signaling in a mouse model of glucocorticoid resistance...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835038/family-matters-collaboration-and-conflict-among-the-steroid-receptors-raises-a-need-for-group-therapy
#11
Matthew J Sikora
Antiestrogen therapies targeting the function of estrogen receptor (ER) have been the cornerstone of therapy for ER+ breast cancer for decades. However, as long as these therapies have been in use, it has also been evident that response to antiestrogen therapy is not based solely on ER expression but that other factors modify breast cancer antiestrogen response. Such factors may include ER's relatives in the steroid hormone receptor (HR) family, androgen receptor (AR), progesterone receptor (PR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR)...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27834956/a-bak-dependent-mitochondrial-amplification-step-contributes-to-smac-mimetic-glucocorticoid-induced-necroptosis
#12
Katharina Rohde, Lara Kleinesudeik, Stefanie Roesler, Oliver Löwe, Juliana Heidler, Katrin Schröder, Ilka Wittig, Stefan Dröse, Simone Fulda
Necroptosis is a form of programmed cell death that critically depends on RIP3 and MLKL. However, the contribution of mitochondria to necroptosis is still poorly understood. In the present study, we discovered that mitochondrial perturbations play a critical role in Smac mimetic/Dexamethasone (Dexa)-induced necroptosis independently of death receptor ligands. We demonstrate that the Smac mimetic BV6 and Dexa cooperate to trigger necroptotic cell death in acute lymphoblastic leukemia (ALL) cells that are deficient in caspase activation due to absent caspase-8 expression or pharmacological inhibition by the caspase inhibitor zVAD...
November 11, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27834289/the-metabolic-effects-of-prazosin-on-skeletal-muscle-insulin-resistance-in-glucocorticoid-treated-male-rats
#13
Emily C Dunford, Erin R Mandel, Sepideh Mohajeri, Tara L Haas, Michael C Riddell
High dose glucocorticoids (GC) induce skeletal muscle atrophy, insulin resistance and reduced muscle capillarization. Identification of treatments to prevent or reverse capillary rarefaction and metabolic deterioration caused by prolonged elevations in GCs would be therapeutically beneficial. Chronic administration of prazosin, α1-adrenergic antagonist, increases skeletal muscle capillarization, in healthy rodents and recently, a rodent model of elevated GCs and hyperglycemia. The purpose of this study was to determine whether prazosin administration would improve glucose tolerance and insulin sensitivity, through prazosin mediated sparing of capillary rarefaction, in this rodent model of increased GC exposure...
November 9, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27833094/enhanced-sensitivity-to-glucocorticoids-in-cytarabine-resistant-aml
#14
D Malani, A Murumägi, B Yadav, M Kontro, S Eldfors, A Kumar, R Karjalainen, M M Majumder, P Ojamies, T Pemovska, K Wennerberg, C Heckman, K Porkka, M Wolf, T Aittokallio, O Kallioniemi
We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27828596/experimental-model-of-glucocorticoid-induced-insulin-resistance
#15
Beatriz Bertolaccini Martínez, Ana Carolina Couto Pereira, Júlio Henrique Muzetti, Fernando de Paiva Telles, Fiorita Gonzáles Lopes Mundim, Manoel Araújo Teixeira
PURPOSE: To evaluate metabolic effects in experimental model of glucocorticoid-induced insulin resistance. METHODS: Twenty Wistar male rats were randomly divided into two groups, which were treated with intraperitoneally injected dexamethasone 1mg/Kg/day for ten days consecutively (Group D; n=10) and placebo (Group C; n=10). The variables analyzed were: from the first to the 10th day - body weight (before and after treatment); food and water daily consumption; on the 10th day - glycemia, insulinemia, HOMA-beta and HOMA-IR...
October 2016: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/27825347/non-neuronal-cholinergic-system-contributes-to-corticosteroid-resistance-in-chronic-obstructive-pulmonary-disease-patients
#16
Javier Milara, Angela Cervera, Alfredo de Diego, Celia Sanz, Gustavo Juan, Amadeu Gavaldà, Montserrat Miralpeix, Esteban Morcillo, Julio Cortijo
BACKGROUND: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect...
November 8, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27824928/carbenoxolone-disodium-treatment-for-canine-pituitary-dependent-hyperadrenocorticism
#17
Takahiro Teshima, Hirotaka Matsumoto, Tomoko Okusa, Rion Uchiyama, Hidekazu Koyama
Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their resistance to negative feedback by glucocorticoids. In some animal species, including dogs, the aberrant expression of 11β-hydroxysteroid dehydrogenase (11HSD), a cortisol metabolic enzyme, is observed in corticotroph tumors. We previously reported that carbenoxolone (CBX), an inhibitor of 11HSD, suppressed ACTH secretion from the pituitary gland, and decreased cortisol concentrations in healthy dogs...
2016: PloS One
https://www.readbyqxmd.com/read/27822713/dexamethasone-alters-the-appetite-regulation-via-induction-of-hypothalamic-insulin-resistance-in-rat-brain
#18
Ragitha Chruvattil, Shreya Banerjee, Sarmi Nath, Jatin Machhi, Gitika Kharkwal, Mange Ram Yadav, Sarita Gupta
Elevated levels of glucocorticoid, a steroid hormone released in response to stress, have been implicated in the pathophysiology of diabetes, which is now known to extend its effect on brain functions. Hence, we aimed to investigate the status of brain insulin signaling in response to dexamethasone (a synthetic glucocorticoid) treatment in female Charles Foster rat. This model exhibited pronounced hyperinsulinemia and glucose intolerance with loss in appetite and body weight. Immunoblotting of insulin receptor (INSR)-PI3kinase-AKT demonstrated reduced insulin signaling in hypothalamus but no change in hippocampus, cortex, and cerebellum in dexamethasone-treated rats as compared to vehicle-treated rats, signifying the diversity of distribution and function of insulin in different brain regions...
November 7, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27817791/-advances-in-clinical-research-on-c1q-nephropathy
#19
Juan Yang, Bi-Li Zhang
C1q nephropathy is a rare type of glomerulonephritis manifested as the deposition of C1q in the glomerular mesangium during immunofluorescent staining. Systemic lupus erythematosus and type I membranoproliferative glomerulonephropathy need to be excluded in the diagnosis of C1q nephropathy. C1q nephropathy has various manifestations under a light microscope, mainly including minimal change disease, focal segmental glomerulosclerosis, and proliferative glomerulonephritis. This disease is mainly manifested as persistent proteinuria or nephrotic syndrome and occurs more frequently in boys...
November 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/27815034/continuous-corticosterone-delivery-via-the-drinking-water-or-pellet-implantation-a-comparative-study-in-mice
#20
Sylvia J Gasparini, Marie-Christin Weber, Holger Henneicke, Sarah Kim, Hong Zhou, Markus J Seibel
In order to investigate the effects of glucocorticoid excess in rodent models, reliable methods of continuous glucocorticoid delivery are essential. The current study compares two methods of corticosterone (CS) delivery in regards to their ability to induce typical adverse outcomes such as fat accrual, insulin resistance, sarcopenia and bone loss. Eight-week-old mice received CS for 4weeks either via the drinking water (25-100μgCS/mL) or through weekly surgical implantation of slow release pellets containing 1...
November 2, 2016: Steroids
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