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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/29158269/the-glucocorticoid-receptor-is-a-key-player-for-prostate-cancer-cell-survival-and-a-target-for-improved-anti-androgen-therapy
#1
Martin Puhr, Julia Hoefer, Andrea Eigentler, Christian Ploner, Florian Handle, Georg Schaefer, Jan Kroon, Angela Leo, Isabel M Heidegger, Iris E Eder, Zoran Culig, Gabri van der Pluijm, Helmut Klocker
PURPOSE: The major obstacle in the management of advanced prostate cancer (PCa) is the occurrence of resistance to endocrine-therapy. Although the androgen receptor (AR) has been linked to therapy failure, the underlying escape mechanisms have not been fully clarified. Being closely related to the AR, the glucocorticoid receptor (GR) has been suggested to play a role in enzalutamide and docetaxel resistance. Given that glucocorticoids are frequently applied to PCa patients, it is essential to unravel the exact role of the GR in PCa progression...
November 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29151100/correlation-between-cosyntropin-stimulation-study-and-disease-severity-in-children-with-fluid-and-catecholamine-refractory-shock-in-the-pediatric-and-cardiovascular-intensive-care-unit
#2
Pallavi Iyer, Brittany Harrington, Jeffrey J Fadrowski, Erica Sibinga, Ernest K Amankwah
BACKGROUND: The cosyntropin stimulation study (CSS) measures the patient's ability to adequately mount a cortisol response. Clinically, CSS results may not be used to guide hydrocortisone use. The objective of this study was to examine how the CSS results are associated with clinical parameters, mortality/disease severity, and use of glucocorticoids in pediatric patients with catecholamine- and fluid-resistant shock. METHODS: This was a retrospective cohort study of patients who had a CSS during 2009-2014 in the intensive care unit at a children's hospital...
November 17, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29146967/splenic-glucocorticoid-resistance-following-psychosocial-stress-requires-physical-injury
#3
Sandra Foertsch, Andrea M Füchsl, Sandra D Faller, Hannah Hölzer, Dominik Langgartner, Joanna Messmann, Gudrun Strauß, Stefan O Reber
Mice exposed to chronic subordinate colony housing (CSC) stress show glucocorticoid (GC) resistance of in vitro lipopolysaccharide (LPS)-stimulated splenocytes, increased anxiety and colitis. Similar effects were reported in wounded mice exposed to social disruption (SDR). Here we show that CSC exposure induced GC resistance in isolated and in vitro LPS-stimulated, but not unstimulated, splenocytes, and these effects were absent when CD11b(+) splenocytes were depleted. Moreover, re-active coping behaviour during CSC correlated with the attacks and bites received by the resident, which in turn highly correlated with the dimension of splenic GC resistance, as with basal and LPS-induced in vitro splenocyte viability...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29145259/impulse-oscillometry-system-as-an-alternative-diagnostic-method-for-chronic-obstructive-pulmonary-disease
#4
Xia Wei, Zhihong Shi, Yajuan Cui, Jiuyun Mi, Zhengquan Ma, Jingting Ren, Jie Li, Shudi Xu, Youmin Guo
We aimed to compare impulse oscillation system (IOS) and traditional pulmonary function tests (PFTs) for the assessment of the severity of chronic obstructive pulmonary disease (COPD), and to assess the use of IOS parameters to identify patients who were forced expiratory volume in 1 second (FEV1)%pred < 50%.Patients with COPD (n = 215) were enrolled at the Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong University between October 2014 and September 2016. All patients were assessed by traditional PFT and IOS...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29141867/host-resistance-to-endotoxic-shock-requires-the-neuroendocrine-regulation-of-group-1-innate-lymphoid-cells
#5
Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, Eric Vivier, Sophie Ugolini
Upon infection, the immune system produces inflammatory mediators important for pathogen clearance. However, inflammation can also have deleterious effect on the host and is tightly regulated. Immune system-derived cytokines stimulate the hypothalamic-pituitary-adrenal (HPA) axis, triggering endogenous glucocorticoid production. Through interaction with ubiquitously expressed glucocorticoid receptors (GRs), this steroid hormone has pleiotropic effects on many cell types. Using a genetic mouse model in which the gene encoding the GR is selectively deleted in NKp46(+) innate lymphoid cells (ILCs), we demonstrated a major role for the HPA pathway in host resistance to endotoxin-induced septic shock...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29138984/11%C3%AE-hydroxysteroid-dehydrogenases-and-hypertension-in-the-metabolic-syndrome
#6
REVIEW
Matthew A Bailey
The metabolic syndrome describes a clustering of risk factors-visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension-that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25-30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome...
November 14, 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/29138818/%C3%AE-%C3%A2-ecdysterone-promotes-autophagy-and-inhibits-apoptosis-in-osteoporotic-rats
#7
Yang-Hua Tang, Zhen-Shuang Yue, Da-Wei Xin, Lin-Ru Zeng, Zhen-Fei Xiong, Zhong-Qing Hu, Can-Da Xu
Osteoporosis is an aging process of skeletal tissues with characteristics of reductions in bone mass and microarchitectural deterioration of bone tissue. The present study aimed to investigate the effects of glucocorticoid‑induced osteoporosis on osteoblasts and to examine the roles of β‑ecdysterone (β‑Ecd) involved. In the present study, an in vivo model of osteoporosis was established through the subcutaneous implantation of prednisolone (PRED) into Sprague‑Dawley rats, with or without a subcutaneous injection of β‑Ecd (5 or 10 mg/kg body weight)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29133777/acute-lymphoblastic-leukemia-patient-with-variant-atf7ip-pdgfrb-fusion-and-favorable-response-to-tyrosine-kinase-inhibitor-treatment-a-case-report
#8
Ge Zhang, Yanle Zhang, Jianrong Wu, Yan Chen, Zhigui Ma
BACKGROUND Chromosomal translocations involving the PDGFRB gene have been reported in a broad spectrum of hematological malignancies. An ATF7IP/PDGFRB fusion was recently identified in a Philadelphia chromosome-like (Ph-like) B-progenitor acute lymphoblastic leukemia (B-ALL) patient. Here we report on a special case of a Ph-like ALL patient who had a variant ATF7IP/PDGFRB fusion. CASE REPORT In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively...
November 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29130617/dendritic-cell-phenotype-in-severe-asthma-reflects-clinical-responsiveness-to-glucocorticoids
#9
Emma S Chambers, Alexandra M Nanzer, Paul E Pfeffer, David F Richards, Adrian R Martineau, Christopher J Griffiths, Christopher J Corrigan, Catherine M Hawrylowicz
BACKGROUND: Subsets of patients with severe asthma remain symptomatic despite prolonged, high dosage glucocorticoid therapy. We hypothesised that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. OBJECTIVE: To compare peripheral blood leukocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid sensitive (SS) and steroid resistant (SR) asthmatics...
November 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29125588/glucocorticoids-cause-gender-dependent-reversal-of-hepatic-fibrosis-in-the-mdr2-knockout-mouse-model
#10
Anca D Petrescu, Stephanie Grant, Gabriel Frampton, Jessica Kain, Karam Hadidi, Elaina Williams, Matthew McMillin, Sharon DeMorrow
Hepatic cholestasis is associated with a significant suppression of the hypothalamus-pituitary-adrenal axis (HPA). In the present study, we tested the hypothesis that activation of the HPA axis by corticosterone treatment can reverse liver inflammation and fibrosis in a multidrug resistance protein 2 knockout (MDR2KO) transgenic mouse model of hepatic cholestasis. Friend Virus B NIH-Jackson (FVBN) control and MDR2KO male and female mice were treated with vehicle or corticosterone for two weeks, then serum and liver analyses of hepatic cholestasis markers were performed...
November 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29122152/biologic-agents-for-the-treatment-of-hypereosinophilic-syndromes
#11
Fei Li Kuang, Amy D Klion
Hypereosinophilic syndromes (HES) are a heterogeneous group of rare disorders defined by the presence of marked peripheral or tissue eosinophilia resulting in end-organ damage. Although conventional therapies, including glucocorticoids, hydroxyurea, and IFN-α, are initially effective in reducing eosinophilia and symptoms in a majority of patients with platelet-derived growth factor mutation-negative HES, the development of resistance and treatment-related toxicity are common. In contrast, targeted therapy with the tyrosine kinase inhibitor, imatinib, is well tolerated but effective only in the subset of patients with HES with a primary myeloid disorder...
November 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29118587/consequences-of-different-corticosteroids-on-serum-potassium-and-prostate-specific-antigen-in-patients-receiving-abiraterone-for-castration-resistant-prostate-cancer-a-retrospective-observational-study
#12
Masaomi Tatsuzawa, Ryuichi Ogawa, Naoki Kinjo, Soan Kim, Fumitaka Shimizu, Yoshiro Sakamoto, Kazuyo Shimojima, Hirotoshi Echizen, Akihisa Miyazaki
Background: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. Methods: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0...
2017: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/29115514/polygonum-multiflorm-alleviates-glucocorticoid%C3%A2-induced-osteoporosis-and-wnt-signaling-pathway
#13
Manru Zhou, Jingkai Wu, Yongjie Yu, Yajun Yang, Jin Li, Liao Cui, Weimin Yao, Yuyu Liu
It is known that long‑term excessive administration of glucocorticoid (GC) results in osteoporosis. The present study aimed to evaluate the protective effects of Polygonum multiflorm (PM) on the bone tissue of rats with GC‑induced osteoporosis (GIO). A total of 90 6‑month‑old female Sprague Dawley rats (weight range, 190‑210 g) were randomly divided into nine groups: Control (normal saline); prednisone (GC; 6 mg·kg‑1·d‑1; Model); GC plus PMR30 (the 30% ethanol eluent fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMR30 (M) (200 mg·kg‑1·d‑1); GC plus PMR30 (L) (100 mg·kg‑1·d‑1); GC plus PMRF (fat‑soluble fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMRF (M) (200 mg·kg‑1·d‑1); GC plus PMRF (L) (100 mg·kg‑1·d‑1); GC plus calcitriol (CAL; 0...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29110911/blau-syndrome-with-good-reponses-to-tocilizumab-a-case-report-and-focused-literature-review
#14
Li Lu, Min Shen, Dongbin Jiang, Yanmin Li, Xiaolong Zheng, Yao Li, Zhixun Li, Leilei Zhang, Jungen Tang, Yanke Guo, Shengyun Liu, Zhaohui Zheng, Guanmin Gao, Quancheng Kan
OBJECTIVES: Blau syndrome (BS), a rare auto-inflammatory granulomatous disease, is a progressive disorder. Usually the maintenance dose of glucocorticoid may not be tapered below 15 mg per day while immunosuppressives is used. There has been some experience with biologic agents in refractory BS patients. The objective of this study is to describe the case of a BS patient benefiting from Tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor. METHODS: We report the first Chinese patient with BS who was resistant to currently available therapies but had rapid quiescence after using Tocilizumab...
September 25, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29110392/nhe3-blockade-ameliorates-type-2-diabetes-mellitus-via-inhibition-of-sglt1-mediated-glucose-absorption-in-the-small-intestine
#15
Leo K Y Chan, Yi Wang, Enders K W Ng, Po Sing Leung
AIM: Na(+) /H(+) exchanger 3 (NHE3) is an exchanger localized to the small intestinal brush border membrane (BBM). Here, we unraveled the role of NHE3 in SGLT1-mediated small intestinal BBM glucose absorption and functional implication in type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Human jejunal samples were obtained from patients undergoing gastrectomy. (14) C-glucose absorption was measured by liquid scintillation counting. NHE3 expression was suppressed by siRNA-mediated knockdown or augmented in Caco2 cells...
November 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29107989/insight-into-glucocorticoid-receptor-signalling-through-interactome-model-analysis
#16
Emyr Bakker, Kun Tian, Luciano Mutti, Constantinos Demonacos, Jean-Marc Schwartz, Marija Krstic-Demonacos
Glucocorticoid hormones (GCs) are used to treat a variety of diseases because of their potent anti-inflammatory effect and their ability to induce apoptosis in lymphoid malignancies through the glucocorticoid receptor (GR). Despite ongoing research, high glucocorticoid efficacy and widespread usage in medicine, resistance, disease relapse and toxicity remain factors that need addressing. Understanding the mechanisms of glucocorticoid signalling and how resistance may arise is highly important towards improving therapy...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29106996/chronic-rhinosinusitis-endotypes-biomarkers-and-treatment-response
#17
Jose Gurrola, Larry Borish
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS impacts prognosis and most importantly is necessary as the basis for making therapeutic decisions. The need for individualized defining of pathogenic mechanisms prior to initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics where, barring an influence from their off-target anti-inflammatory pharmacological effects, an understanding of the role of individual biome predicts likelihood of therapeutic benefit...
October 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29106815/high-dose-glucocorticoids-treatment-does-not-induce-severe-hyperglycemia-in-young-patients-with-autoimmune-diseases-by-cgms
#18
Ying Zhou, Yan Zhao, Tao Yuan, Nan Jiang, Yingyue Dong, Yunjiao Yang, Li Wang, Jiuliang Zhao, Le Min, Weigang Zhao
INTRODUCTION: High-dose glucocorticoids (HDG) are used in the treatment of autoimmune diseases. Glucocorticoids-induced hyperglycemia (GIH) is often described in elderly patients. In young patients with autoimmune diseases, however, the risk for GIH has not been well characterized. METHODS: Twenty-four inpatients (median age 32 years (interquatile range 25-42)) with exacerbations of autoimmune diseases, receiving 1-2mg/kg/day prednisone or equivalent methylprednisone, were recruited...
November 6, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29101238/glucocorticoid-resistance-is-reverted-by-lck-inhibition-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#19
Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocorticoid (GC) treatment. These patients, classified as Prednisone Poor Responders (PPR), have poorer outcome compared to the other pediatric T-ALL patients receiving a high-risk adapted therapy. Since glucocorticoids are administered to ALL patients during all the different phases of therapy, GC resistance represents an important challenge to be addressed in order to improve the outcome for these patients. Mechanisms underlying resistance are not yet fully unraveled, thus our research focused on the identification of deregulated signaling pathways to point out new targeted approaches...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29098400/histone-deacetylase-2-expression-and-activity-in-children-with-nephrotic-syndrome-with-different-glucocorticoid-response
#20
Feng-Jun Guan, Qian-Qian Peng, Lin-Li Wang, Xue-Bo Yan, Chen Dong, Xiao-Hua Jiang
BACKGROUND: Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children...
November 2, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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