%0 Journal Article %J Clin Pharmacol Ther %D 2016 %T In vitro sensitivity to methyl-prednisolone is associated with clinical response in pediatric idiopathic nephrotic syndrome. %A Cuzzoni, E %A De Iudicibus, S %A Stocco, G %A Favretto, D %A Pelin, M %A Messina, G %A Ghio, L %A Monti, E %A Pasini, A %A Montini, G %A Decorti, G %X

The aim of this study was to evaluate the in vitro steroid sensitivity as a predictor of clinical response to glucocorticoids in childhood idiopathic nephrotic syndrome (INS). Seventy-four patients (median age 4.33, interquartile range [IQR] 2.82-7.23; 63.5% male) were enrolled in a prospective multicenter study: in vitro steroid inhibition of patients' peripheral blood mononuclear cell proliferation was evaluated by [methyl-(3) H] thymidine incorporation assay at disease onset (T0) and after 4 weeks (T4) of treatment. Steroid dependence was associated with increased in vitro sensitivity at T4 assessed both as drug concentration inducing 50% of inhibition (IC50 ; odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24-0.85; P = 0.0094) and maximum inhibition at the highest drug concentration (Imax ; OR = 1.13, 95% CI = 1.02-1.31; P = 0.017). IC50 > 4.4 nM and Imax < 92% at T4 were good predictors for optimal clinical response. These results suggest that this test may be useful for predicting the response to glucocorticoid therapy in pediatric INS.

%B Clin Pharmacol Ther %V 100 %P 268-74 %8 2016 Sep %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27007551?dopt=Abstract %R 10.1002/cpt.372 %0 Journal Article %J Curr Mol Med %D 2015 %T Long noncoding RNA GAS5: a novel marker involved in glucocorticoid response. %A Lucafo, M %A De Iudicibus, S %A Di Silvestre, A %A Pelin, M %A Candussio, L %A Martelossi, S %A Tommasini, A %A Piscianz, E %A Ventura, A %A Decorti, G %K Adult %K Cell Proliferation %K Female %K Gene Expression Regulation %K Glucocorticoids %K Humans %K Leukocytes, Mononuclear %K Male %K Methylprednisolone %K Middle Aged %K Receptors, Glucocorticoid %K RNA, Long Noncoding %K Transcription, Genetic %X

Glucocorticoids (GCs) exert their effects through regulation of gene expression after activation in the cytoplasm of the glucocorticoid receptor (GR) encoded by NR3C1 gene. A negative feedback mechanism resulting in GR autoregulation has been demonstrated through the binding of the activated receptor to intragenic sequences called GRE-like elements, contained in GR gene. The long noncoding RNA growth arrest-specific transcript 5 (GAS5) interacts with the activated GR suppressing its transcriptional activity. The aim of this study was to evaluate the possible role of GAS5 and NR3C1 gene expression in the antiproliferative effect of methylprednisolone in peripheral blood mononuclear cells and to correlate the expression with individual sensitivity to GCs. Subjects being poor responders to GCs presented higher levels of GAS5 and NR3C1 in comparison with good responders. We suggest that abnormal levels of GAS5 may alter GC effectiveness, probably interfering with the mechanism of GR autoregulation.

%B Curr Mol Med %V 15 %P 94-9 %8 2015 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/25601472?dopt=Abstract %0 Journal Article %J Aliment Pharmacol Ther %D 2012 %T Letter: TPMT activity and age in IBD patients. %A Stocco, G %A De Iudicibus, S %A Cuzzoni, E %A Decorti, G %A Martelossi, S %A Ventura, A %K Azathioprine %K Humans %K Immunosuppressive Agents %K Inflammatory Bowel Diseases %K Thioguanine %B Aliment Pharmacol Ther %V 35 %P 966-7; author reply 967-9 %8 2012 Apr %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/22436044?dopt=Abstract %R 10.1111/j.1365-2036.2012.05027.x