@article {10510,
	title = {Role of the Long Non-Coding RNA Growth Arrest-Specific 5 in Glucocorticoid Response in Children with Inflammatory Bowel Disease.},
	journal = {Basic Clin Pharmacol Toxicol},
	volume = {122},
	year = {2018},
	month = {2018 Jan},
	pages = {87-93},
	abstract = {<p>Glucocorticoids (GCs) are widely employed in inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in inflammatory bowel disease (IBD). Given the high incidence of suboptimal response, associated with a significant number of side-effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to respond poorly to GCs is extremely important. Recent evidence suggests that the long non-coding RNA (lncRNA) GAS5 could be a potential marker of GC resistance. To address this issue, we evaluated the association between the lncRNA GAS5 and the efficacy of steroids, in terms of inhibition of proliferation, in two cell lines derived from colon and ovarian cancers, to confirm the sensitivity and specificity of these lncRNAs. These cells showed a different sensitivity to GCs and revealed differential expression of GAS5 after treatment. GAS5 was up-regulated in GC-resistant cells and accumulated more in the cytoplasm compared to the nucleus in response to the drug. The functions of GAS5 were assessed by silencing, and we found that GAS5 knock-down reduced the proliferation during GC treatment. Furthermore, for the first time, we measured GAS5 levels in 19 paediatric IBD patients at diagnosis and after the first cycle of GCs, and we demonstrated an up-regulation of the lncRNA in patients with unfavourable steroid response. Our preliminary results indicate that GAS5 could be considered a novel pharmacogenomic marker useful for the personalization of GC therapy.</p>},
	keywords = {Biomarkers, Cell Line, Tumor, Cell Proliferation, Child, Drug Resistance, Female, Gene Knockdown Techniques, Glucocorticoids, Humans, Inflammatory Bowel Diseases, Male, Patient Selection, Pharmacogenomic Testing, Precision Medicine, RNA, Long Noncoding, RNA, Small Interfering, Treatment Outcome, Up-Regulation},
	issn = {1742-7843},
	doi = {10.1111/bcpt.12851},
	author = {Lucaf{\`o}, Marianna and Di Silvestre, Alessia and Romano, Maurizio and Avian, Alice and Antonelli, Roberta and Martelossi, Stefano and Naviglio, Samuele and Tommasini, Alberto and Stocco, Gabriele and Ventura, Alessandro and Decorti, Giuliana and De Iudicibus, Sara}
}
@article {7779,
	title = {Role of oxidative stress mediated by glutathione-s-transferase in thiopurines{\textquoteright} toxic effects.},
	journal = {Chem Res Toxicol},
	volume = {28},
	year = {2015},
	month = {2015 Jun 15},
	pages = {1186-95},
	abstract = {<p>Azathioprine (AZA), 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) are antimetabolite drugs, widely used as immunosuppressants and anticancer agents. Despite their proven efficacy, a high incidence of toxic effects in patients during standard-dose therapy is recorded. The aim of this study is to explain, from a mechanistic point of view, the clinical evidence showing a significant role of glutathione-S-transferase (GST)-M1 genotype on AZA toxicity in inflammatory bowel disease patients. To this aim, the human nontumor IHH and HCEC cell lines were chosen as predictive models of the hepatic and intestinal tissues, respectively. AZA, but not 6-MP and 6-TG, induced a concentration-dependent superoxide anion production that seemed dependent on GSH depletion. N-Acetylcysteine reduced the AZA antiproliferative effect in both cell lines, and GST-M1 overexpression increased both superoxide anion production and cytotoxicity, especially in transfected HCEC cells. In this study, an in vitro model to study thiopurines{\textquoteright} metabolism has been set up and helped us to demonstrate, for the first time, a clear role of GST-M1 in modulating AZA cytotoxicity, with a close dependency on superoxide anion production. These results provide the molecular basis to shed light on the clinical evidence suggesting a role of GST-M1 genotype in influencing the toxic effects of AZA treatment.</p>},
	issn = {1520-5010},
	doi = {10.1021/acs.chemrestox.5b00019},
	author = {Pelin, Marco and De Iudicibus, Sara and Fusco, Laura and Taboga, Eleonora and Pellizzari, Giulia and Lagatolla, Cristina and Martelossi, Stefano and Ventura, Alessandro and Decorti, Giuliana and Stocco, Gabriele}
}
