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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/28648630/resolution-of-a-steroid-resistant-hypereosinophilic-immune-diathesis-with-mepolizumab-and-concomitant-amelioration-of-a-mixed-thrombotic-microangiopathy
#1
J Justin Mulvey, Cynthia Magro, Amy Chadburn
The anaphylatoxins produced by an unbridled complement cascade in atypical hemolytic uremic syndrome (aHUS) can alter the leukocyte environment in tissues and peripheral blood, causing clinically significant eosinophilia. While the membrane attack complex and C5a anaphlatoxin can be suppressed with anti-C5 biologics, the production of C3a is still capable of driving a destructive hypereosinophilic syndrome in spite of anticomplement therapy. The side-effects of glucocorticoids in treating hypereosinophilic syndrome limit their therapeutic index in long-term treatment and this behooves the use of alternative strategies...
May 2, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28647094/long-term-prognosis-of-hematogenous-vertebral-osteomyelitis-mortality-quality-of-life-and-pain
#2
Terufumi Kokabu, Masahiko Takahata, Nobuhisa Ishiguro, Norimasa Iwasaki
BACKGROUND: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. METHODS: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course...
June 21, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#3
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28645097/raman-spectroscopy-differentiates-between-sensitive-and-resistant-multiple-myeloma-cell-lines
#4
Domenico Franco, Sebastiano Trusso, Enza Fazio, Alessandro Allegra, Caterina Musolino, Antonio Speciale, Francesco Cimino, Antonella Saija, Fortunato Neri, Marco S Nicolò, Salvatore P P Guglielmino
Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM...
June 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28641635/-application-of-mir-182-for-determination-of-glucocorticoid-resistant-patients-with-lymphoid-malignancy
#5
Ying-Wei Hu, Shi-Yu Chen, Yan-Hui Xie
OBJECTIVE: To validate the clinical relationship between miR-182 and glucocorticoid-resistance in patients with lymphoid malignancy. METHODS: Real-time quantitative PCR(qRT-PCR) was employed to detect the expression of miR-182 in lymphoma patients (68 cases, the specimens indluded bone marrow of 20 cases, and plasma of 48 cases), multiple myeloma patients (24 cases, the specimens included bone marrow of 14 cases and plasma of 10 cases), ALL patients (3 cases, specimen was plasma of 3 cases) and non-lymphotic system disorder patients (18 cases, specimens included bone marrow of 8 cases and plasma of 10 cases)...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641145/lack-of-association-between-deletion-polymorphism-of-bim-gene-and-in-vitro-drug-sensitivity-in-b-cell-precursor-acute-lymphoblastic-leukemia
#6
Meixian Huang, Kunio Miyake, Keiko Kagami, Masako Abe, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Nobutaka Kiyokawa, Kanji Sugita, Takeshi Inukai
A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy...
June 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28619709/loss-of-fam46c-promotes-cell-survival-in-myeloma
#7
Yuan Xiao Zhu, Chang-Xin Shi, Laura A Bruins, Patrick Jedlowski, Xuewei Wang, K Martin Kortüm, Moulun Luo, Jonathan Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28609678/glucocorticoid-mediated-activation-of-gsk3%C3%AE-promotes-tau-phosphorylation-and-impairs-memory-in-type-2-diabetes
#8
Aditi Dey, Shuai Hao, Marlena Wosiski-Kuhn, Alexis M Stranahan
Type 2 diabetes is increasingly recognized as a risk factor for Alzheimer's disease, but the underlying mechanisms remain poorly understood. Hyperphosphorylation of the microtubule-associated protein tau has been reported in rodent models of diabetes, including db/db mice, which exhibit insulin resistance and chronically elevated glucocorticoids due to leptin receptor insufficiency. In this report, we investigated endocrine mechanisms for hippocampal tau phosphorylation in db/db and wild-type mice. By separately manipulating peripheral and intrahippocampal corticosterone levels, we determined that hippocampal corticosteroid exposure promotes tau phosphorylation and activates glycogen synthase kinase 3β (GSK3β)...
May 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#9
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28585089/combination-of-cationic-dexamethasone-derivative-and-stat3-inhibitor-wp1066-for-aggressive-melanoma-a-strategy-for-repurposing-a-phase-i-clinical-trial-drug
#10
Samaresh Sau, Sujan Kumar Mondal, Sushil K Kashaw, Arun K Iyer, Rajkumar Banerjee
Glucocorticoid, such as dexamethasone (Dex) is often used along with chemotherapy to antagonize side effects of chemotherapy. However, sustained use of Dex frequently develops drug resistance in patients. As a strategy to re-induce drug sensitivity, we planned to modify Dex by chemically conjugating it with twin ten carbon aliphatic chain containing cationic lipid. The resultant molecule, DX10, inhibited STAT3 activation through lowering the production of IL-6. To enhance the STAT3 inhibitory effect of DX10, we used WP (a commercially available STAT3 inhibitor) along with DX10...
June 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28582465/differential-regulation-of-cell-death-pathways-by-the-microenvironment-correlates-with-chemoresistance-and-survival-in-leukaemia
#11
Malak Yahia Qattan, Emyr Yosef Bakker, Ramkumar Rajendran, Daphne Wei-Chen Chen, Vaskar Saha, Jizhong Liu, Leo Zeef, Jean-Marc Schwartz, Luciano Mutti, Constantinos Demonacos, Marija Krstic-Demonacos
Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM)...
2017: PloS One
https://www.readbyqxmd.com/read/28580301/adipose-stem-cells-from-obese-patients-show-specific-differences-in-the-metabolic-regulators-vitamin-d-and-gas5
#12
Laura M Pérez, Beatriz de Lucas, Victoria V Lunyak, Beatriz G Gálvez
Adipose tissue is a significant source of mesenchymal stem cells for regenerative therapies; however, caution should be taken as their environmental niche can affect their functional properties. We have previously demonstrated the negative impact of obesity on the function of adipose-derived stem cells (ASCs). Here we have evaluated other possible properties and targets that are altered by obesity such as the recently described long non-coding molecule Gas5, which is involved in glucocorticoid resistance. Using ASCs isolated from obese (oASCs) and control subjects (cASCs), we have analyzed additional metabolic and inflammatory conditions that could be related with their impaired therapeutic potential and consequently their possible usefulness in the clinic...
September 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28578424/aminophylline-restores-glucocorticoid-sensitivity-in-a-guinea-pig-model-of-sudden-sensorineural-hearing-loss-induced-by-lipopolysaccharide
#13
Qiong-Qiong Zhou, Yan-Hong Dai, Xiao-Ping Du, Jie Hou, Hui Qi, Wan-Dong She
Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578002/mir-124-contributes-to-glucocorticoid-resistance-in-acute-lymphoblastic-leukemia-by-promoting-proliferation-inhibiting-apoptosis-and-targeting-the-glucocorticoid-receptor
#14
Yan-Ni Liang, Yan-Lai Tang, Zhi-Yong Ke, Yue-Qin Chen, Xue-Qun Luo, Hua Zhang, Li-Bin Huang
Acute lymphoblastic leukemia (ALL) is characterized by the accumulation of abnormal lymphoblasts in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, some children with ALL still relapsed. Glucocorticoid (GC) resistance is an important clinical problem for ALL treatment failure. Therefore, further understanding of the mechanism of GC resistance and exploring novel therapeutic strategies are crucial for improving treatment outcome. The reported involvement of microRNAs (miRNAs) in drug resistance implied that deregulated miRNA expression might contribute to GC treatment response of ALL...
May 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28551889/maternal-magnesium-restriction-elevates-glucocorticoid-stress-and-inflammation-in-the-placenta-and-fetus-of-wnin-rat-dams
#15
Anju Elizabeth Thomas, Padmavathi J N Inagadapa, Sugeetha Jeyapal, Naga Muralidhar Merugu, Rajender Rao Kalashikam, Raghunath Manchala
Magnesium plays a major role in many vital functions in the body. We reported earlier that maternal magnesium restriction altered body composition, fat metabolism, and insulin resistance in WNIN rat offspring and was associated with increased glucocorticoid stress in the offspring in their later life. We hypothesize that increased glucocorticoid stress and inflammation which originate in Mg restricted rat dams is transmitted through placenta to the fetus and underlie the metabolic disturbances in the later life of the offspring...
May 27, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28551822/glucocorticoid-therapy-causes-contradictory-changes-of-serum-wnt-signaling-related-molecules-in-systemic-autoimmune-diseases
#16
Mai Kawazoe, Kaichi Kaneko, Kotaro Shikano, Natsuko Kusunoki, Toshihiro Nanki, Shinichi Kawai
The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation...
May 27, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28539578/drug-induced-inhibition-of-angiotensin-converting-enzyme-and-dipeptidyl-peptidase-4-results-in-nearly-therapy-resistant-bradykinin-induced-angioedema-a-case-report
#17
Janina Hahn, Susanne Trainotti, Thomas K Hoffmann, Jens Greve
BACKGROUND Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. CASE REPORT We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue...
May 25, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28535268/evaluation-of-the-glucocorticoid-receptor-as-a-biomarker-of-treatment-response-in-vogt-koyanagi-harada-disease
#18
Cristhian A Urzua, Julia Guerrero, Hector Gatica, Victor Velasquez, Annelise Goecke
Purpose: This study is aimed to investigate the role of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMC) as biomarkers of glucocorticoid (GC) resistance and to validate a set of clinical predictive factors in patients with Vogt-Koyanagi-Harada (VKH) disease. Methods: This was a prospective cohort study that included a total of 21 patients with VKH. A complete ophthalmologic evaluation was carried out at baseline that recorded the presence of any clinical predictive factors (visual acuity ≤ 20/200, tinnitus, chronic disease, and fundus depigmentation)...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28529722/recent-advances-in-understanding-cushing-disease-resistance-to-glucocorticoid-negative-feedback-and-somatic-usp8-mutations
#19
REVIEW
Eleni Daniel, John Newell-Price
Cushing's disease is a rare disease with a characteristic phenotype due to significant hypercortisolism driven by over-secretion of adrenocorticotropic hormone and to high morbidity and mortality if untreated. It is caused by a corticotroph adenoma of the pituitary, but the exact mechanisms leading to tumorigenesis are not clear. Recent advances in molecular biology such as the discovery of somatic mutations of the ubiquitin-specific peptidase 8 ( USP8) gene allow new insights into the pathogenesis, which could be translated into exciting and much-needed therapeutic applications...
2017: F1000Research
https://www.readbyqxmd.com/read/28528362/budesonide-fluticasone-propionate-and-azithromycin-do-not-modulate-the-membrane-vesicle-release-by-thp-1-macrophages-and-respiratory-pathogens-during-macrophage-infection
#20
Charlotte Volgers, Gert E Grauls, Pauline H M Hellebrand, Paul H M Savelkoul, Frank R M Stassen
Patients with more severe chronic obstructive pulmonary disease frequently experience exacerbations and it is estimated that up to 50% of these exacerbations are associated with bacterial infections. The mainstay treatment for these infection-related exacerbations constitutes the administration of glucocorticoids, alone or in combination with antibiotics. A recent line of evidence demonstrates that many hormones including the steroid beclomethasone can also directly affect bacterial growth, virulence, and antibiotic resistance...
May 20, 2017: Inflammopharmacology
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