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Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

World Journal of Gastroenterology 2017年第36期23卷 6628-6638页

作者： Karen Dubois-Camacho Payton A Ottum Daniel Franco-Munoz Marjorie De la Fuente Alejandro Torres-Riquelme David Díaz-Jiménez Mauricio Olivares-Morales Gonzalo Astudillo Rodrigo Quera marcela a hermoso Innate Immunity Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile Neuroimmunology Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile Division of Research Clínica Las Condes Gastroenterology Department Inflammatory Bowel Disease ProgramClínica Las Condes

Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible *** glucocorticoids(GCs)are widely used as anti-inflammatory therapy in *** the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of ***,this treatment often results in detrimental side *** downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery *** clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse *** remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to *** this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with *** thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

关键词： Inflammatory bowel diseases Ulcerative colitis Crohn's disease Glucocorticoid dependence Glucocorticoid resistance

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Soluble ST2:A new and promising activity marker in ulcerative colitis

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World Journal of Gastroenterology 2011年第17期17卷 2181-2190页

作者： David Díaz-Jiménez Lucía E Núez Caroll J Beltrán Enzo Candia Cristóbal Suazo Manuel varez-Lobos María-Julieta González marcela a hermoso Rodrigo Quera Disciplinary Program of Immunology Institute of Biomedical SciencesFaculty of MedicineUniversidad de ChileSantiagoCL 8380453Chile Department of Clinical Investigation Hospital Clínico de la Universidad de ChileSantiagoCL 8380456Chile Laboratory of Oncology and Molecular Genetics Colorectal Surgery UnitClínica Las CondesLo Fontecilla 441SantiagoCL 7591046Chile Department of Gastroenterology Pontificia Universidad Católica de ChileSantiagoCL 8380074Chile Cell and Molecular Biology Program Biomedical Sciences InstituteFaculty of MedicineUniversidad de ChileSantiagoCL 8380453Chile Gastroenterology Unit Department of Internal MedicineHospital Clínico de la Universidad de ChileSantiagoCL 8380456Chile Gastroenterology Unit Clínica Las CondesLo Fontecilla 441SantiagoCL 7591046Chile

AIM:To correlate circulating soluble ST2(sST2) levels with the severity of ulcerative colitis(UC) and serum levels of pro-inflammatory cytokines,and to demonstrate the predictive power of sST2 levels for differentiation between active and inactive ***:We recruited 153 patients:82 with UC,26 with Crohn's disease(CD) and 43 disease controls [non-inflammatory bowel disease(IBD)].Subjects were excluded if they had diagnosis of asthma,autoimmune diseases or *** serum levels of sST2 and pro-inflammatory cytokines [pg/mL;median(25th-75th)] as well as clinical features,endoscopic and histological features,were subjected to *** sST2 performance for discrimination between active and inactive UC,non-IBD and healthy controls(HC) was determined with regard to sensitivity and specificity,and Spearman's rank correlation coefficient(r).To validate the method,the area under the curve(AUC) of receiver-operator characteristic(ROC) was determined(AUC,95% CI) and the total ST2 content of the colonic mucosa in UC patients was correlated with circulating levels of ***:The serum sST2 value was significantly higher in patients with active [235.80(90.65-367.90) pg/mL] rather than inactive UC [33.19(20.04-65.32) pg/mL],based on clinical,endoscopic and histopathological characteristics,as well as compared with non-IBD and HC(P < 0.001).The median level of sST2 in CD patients was 54.17(35.02-122.0) pg/mL,significantly higher than that of the HC group only(P < 0.01).The cutoff was set at 74.87 pg/mL to compare active with inactive UC in a multicenter cohort of *** of sensitivity,specificity,and ability to correctly classify UC,according to activity,were 83.33%,83.33% and 83.33%,*** AUC of the ROC curve to assess the ability of this molecule to discriminate between active vs inactive UC was 0.92(0.86-0.97,P < 0.0001).The serum levels of sST2 in patients with UC significantly correlated with endoscopic and histo-pathological scores(r =

关键词： Inflammatory bowel disease Ulcerative colitis Soluble ST2 Biomarkers

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