<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Lucafò, Marianna</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Selvestrel, Davide</style></author><author><style face="normal" font="default" size="100%">Curci, Debora</style></author><author><style face="normal" font="default" size="100%">Pugnetti, Letizia</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pharmacogenetics of treatments for inflammatory bowel disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Expert Opin Drug Metab Toxicol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Expert Opin Drug Metab Toxicol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">Epigenesis, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Gastrointestinal Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Markers</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Pharmacogenetics</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">14</style></volume><pages><style face="normal" font="default" size="100%">1209-1223</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;INTRODUCTION: &lt;/b&gt;Inflammatory bowel disease is a chronic inflammation of the gut whose pathogenesis is still unclear. Although no curative therapy is currently available, a number of drugs are used in induction and maintenance therapy; however, for most of these drugs, a high inter-individual variability in response is observed. Among the factors of this variability, genetics plays an important role. Areas covered: This review summarizes the results of pharmacogenetic studies, considering the most important drugs used and in particular aminosalycilates, glucocorticoids, thiopurines, monoclonal antibodies and thalidomide. Most studies used a candidate gene approach, even if significant breakthroughs have been obtained recently from applying genome-wide studies. When available, also investigations considering epigenetics and pharmacogenetic dosing guidelines have been included. Expert opinion: Only for thiopurines, genetic markers identified as predictors of efficacy or adverse events have allowed the development of dosing guidelines. For the other drugs, encouraging results are available and great expectations rely on the study of epigenetics and integration with pharmacokinetic information, especially useful for biologics. However, to improve therapy of IBD patients with these drugs, for implementation in the clinics of pharmacogenetics, informatic clinical decision support systems and training about pharmacogenetics of health providers are needed.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/30465611?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Granzotto, Marilena</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Rabusin, Marco</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Epratuzumab and Blinatumomab as Therapeutic Antibodies for Treatment of Pediatric Acute Lymphoblastic Leukemia: Current Status and Future Perspectives.</style></title><secondary-title><style face="normal" font="default" size="100%">Curr Med Chem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Curr. Med. Chem.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Antibodies, Bispecific</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Monoclonal</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Monoclonal, Humanized</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Clinical Trials as Topic</style></keyword><keyword><style  face="normal" font="default" size="100%">Half-Life</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Precursor Cell Lymphoblastic Leukemia-Lymphoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Sialic Acid Binding Ig-like Lectin 2</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">24</style></volume><pages><style face="normal" font="default" size="100%">1050-1065</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;More than 85% of children affected by acute lymphoblastic leukemia (ALL) are successfully treated; however relapse remains a remarkable clinical concern, with 50-60% of relapsing patients facing a fatal outcome. Management of relapsed patients includes standardized intensive risk-adapted regimens based on conventional drugs, and hematopoietic stem cells transplantation for patients with unfavourable features. Biological drugs, in particular the monoclonal antibody epratuzumab and the bi-functional recombinant single chain peptide blinatumomab, have been recently recognized as novel potential agents to be integrated in salvage ALL therapy to further improve rescue outcome.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;A systematic search of peer-reviewed scientific literature and clinical trials in public databases has been carried out. Both clinical and pre-clinical studies have been included to summarize recent evidence on epratuzumab and blinatumomab for salvage ALL therapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Sixty-two papers and 25 clinical trials were included. Although not all patients responded properly to these agents, their use in relapsed and refractory pediatric ALL seems promising.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Phase 3 studies have recently begun and more consistent results about epratuzumab and blinatumomab safety and efficacy in comparison to conventional therapies are expected in the next years. Epratuzumab seems safe in the dosing scheme proposed in ALL, but its efficacy over the conventional chemotherapy is still questionable. Blinatumomab has shown promising results in high risk cases such as elder adult patients and conclusive studies on pediatric ALL are needed. Patient inter-individual variability to these agents has not been investigated in depth, but this issue needs to be addressed, in particular for blinatumomab.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28088906?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Arrigo, Serena</style></author><author><style face="normal" font="default" size="100%">Barabino, Arrigo</style></author><author><style face="normal" font="default" size="100%">Aloi, Marina</style></author><author><style face="normal" font="default" size="100%">Martinelli, Massimo</style></author><author><style face="normal" font="default" size="100%">Miele, Erasmo</style></author><author><style face="normal" font="default" size="100%">Knafelz, Daniela</style></author><author><style face="normal" font="default" size="100%">Romano, Claudio</style></author><author><style face="normal" font="default" size="100%">Naviglio, Samuele</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Cuzzoni, Eva</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Multicentric Case-Control Study on Azathioprine Dose and Pharmacokinetics in Early-onset Pediatric Inflammatory Bowel Disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Inflamm Bowel Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Inflamm. Bowel Dis.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Age of Onset</style></keyword><keyword><style  face="normal" font="default" size="100%">Antimetabolites</style></keyword><keyword><style  face="normal" font="default" size="100%">Azathioprine</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Chromatography, High Pressure Liquid</style></keyword><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">Erythrocytes</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Guanine Nucleotides</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mercaptopurine</style></keyword><keyword><style  face="normal" font="default" size="100%">Methyltransferases</style></keyword><keyword><style  face="normal" font="default" size="100%">Thioguanine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 04</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">23</style></volume><pages><style face="normal" font="default" size="100%">628-634</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Early-onset inflammatory bowel disease (IBD) is generally aggressive, with a high probability of complications and need of surgery. Despite the introduction of highly effective biological drugs, treatment with azathioprine continues to be important even for early-onset IBD; however, in these patients azathioprine response seems to be reduced. This study evaluated azathioprine doses, metabolite concentrations, and their associations with patients' age in children with IBD treated at 6 tertiary pediatric referral centers.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Azathioprine doses, metabolites, and clinical effects were assessed after at least 3 months of therapy in 17 early-onset (age &lt; 6 yr, cases) and 51 nonearly-onset (aged &gt; 12 and &lt;18 yrs, controls) patients with IBD. Azathioprine dose was titrated on therapeutic efficacy (response and adverse effects). Azathioprine metabolites and thiopurine methyltransferase activity were determined by high-performance liquid chromatography with ultra violet-vis detection (HPLC-UV) methods.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Frequency of patients in remission was similar among early-onset and control groups, respectively (82% and 84%, P value = 0.72). Early-onset patients required higher doses of azathioprine (median 2.7 versus 2.0 mg·kg·d, P value = 1.1 × 10). Different doses resulted in comparable azathioprine active thioguanine nucleotide metabolite concentrations (median 263 versus 366 pmol/8 × 10 erythrocytes, P value = 0.41) and methylmercaptopurine nucleotide concentrations (median 1455 versus 1532 pmol/8 × 10 erythrocytes, P value = 0.60). Lower ratios between thioguanine nucleotide metabolites and azathioprine doses were found in early-onset patients (median 98 versus 184 pmol/8 × 10 erythrocytes·mg·kg·d, P value = 0.017). Interestingly, early-onset patients presented also higher thiopurine methyltransferase activity (median 476 versus 350 nmol methylmercaptopurine/mg hemoglobin/h, P-value = 0.046).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;This study demonstrated that patients with early-onset IBD present increased inactivating azathioprine metabolism, likely because of elevated activity of the enzyme thiopurine methyltransferase.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28296824?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Cuzzoni, Eva</style></author><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Lucafò, Marianna</style></author><author><style face="normal" font="default" size="100%">Pelin, Marco</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Pasini, Andrea</style></author><author><style face="normal" font="default" size="100%">Montini, Giovanni</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome.</style></title><secondary-title><style face="normal" font="default" size="100%">Pharmacogenomics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Pharmacogenomics</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">1631-48</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Idiopathic nephrotic syndrome represents the most common type of primary glomerular disease in children: glucocorticoids (GCs) are the first-line therapy, even if considerable interindividual differences in thepir efficacy and side effects have been reported. Immunosuppressive and anti-inflammatory effects of these drugs are mainly due to the GC-mediated transcription regulation of pro- and anti-inflammatory genes. This mechanism of action is the result of a complex multistep pathway that involves the glucocorticoid receptor and several other proteins, encoded by polymorphic genes. Aim of this review is to highlight the current knowledge on genetic variants that could affect GC response, particularly focusing on children with idiopathic nephrotic syndrome.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">14</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26419298?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Giurici, Nagua</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Rabusin, Marco</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.</style></title><secondary-title><style face="normal" font="default" size="100%">Int J Mol Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Int J Mol Sci</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">18601-27</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26266406?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Pelin, Marco</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Cuzzoni, Eva</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?</style></title><secondary-title><style face="normal" font="default" size="100%">World J Gastroenterol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">World J. Gastroenterol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">6-Mercaptopurine</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Azathioprine</style></keyword><keyword><style  face="normal" font="default" size="100%">Glutathione</style></keyword><keyword><style  face="normal" font="default" size="100%">Glutathione Transferase</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunosuppressive Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidative Stress</style></keyword><keyword><style  face="normal" font="default" size="100%">Pharmacogenetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Apr 7</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">20</style></volume><pages><style face="normal" font="default" size="100%">3534-41</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease (IBD). In vivo it is active after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of isoforms M and A of the enzyme glutathione-S-transferase (GST) may increase its speed. Indeed, in pediatric patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites. In addition to increase the activation of azathioprine to mercaptopurine, GSTs may contribute to azathioprine effects even by modulating GSH consumption, oxidative stress and apoptosis. Therefore, genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">13</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24707136?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Rebora, Paola</style></author><author><style face="normal" font="default" size="100%">Athanasakis, Emmanouil</style></author><author><style face="normal" font="default" size="100%">Favretto, Diego</style></author><author><style face="normal" font="default" size="100%">Verzegnassi, Federico</style></author><author><style face="normal" font="default" size="100%">Basso, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Tommasini, Alberto</style></author><author><style face="normal" font="default" size="100%">Valsecchi, Maria Grazia</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Rabusin, Marco</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TNF-α SNP rs1800629 and risk of relapse in childhood acute lymphoblastic leukemia: relation to immunophenotype.</style></title><secondary-title><style face="normal" font="default" size="100%">Pharmacogenomics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Pharmacogenomics</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Neoplasm</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Leukemia, Lymphocytic, Chronic, B-Cell</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Precursor Cell Lymphoblastic Leukemia-Lymphoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Recurrence</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Assessment</style></keyword><keyword><style  face="normal" font="default" size="100%">Steroids</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Necrosis Factor-alpha</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Apr</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">619-27</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;AIM: &lt;/b&gt;In the AIEOP-BFM ALL (Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt Münster acute lymphoblastic leukemia) 2000 protocol, 70% of relapsed patients had favorable prognostic features and fell within less intensive polychemotherapeutic regimens, suggesting the need for better assessing lower risk stratification.&lt;/p&gt;&lt;p&gt;&lt;b&gt;MATERIALS &amp; METHODS: &lt;/b&gt;A novel two-phase study design selected 614 children to be genotyped for TNF-α SNP rs1800629 (-308G&gt;A). A weighted Cox model was applied to evaluate the SNP effect on hazard of relapse, adjusting for immunophenotype, risk group, age and gender and including interaction terms.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Significant interaction was found with immunophenotypes (p = 0.0007, with minor allele genotypes being adverse genetic markers in B-cell acute lymphoblastic leukemia and protective ones in T-cell acute lymphoblastic leukemia), and also with risk protocols (p = 0.0041, with minor allele genotypes as prognostic factor of relapse for standard risk patients [only one T-cell acute lymphoblastic leukemia in the subgroup analyzed]).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;The presence of at least one A allele in TNF-α SNP rs1800629 should suggest a closer monitoring in B-cell acute lymphoblastic leukemia standard risk patients.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24798719?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Addobbati, Riccardo</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Personalized therapies in pediatric inflammatory and autoimmune diseases.</style></title><secondary-title><style face="normal" font="default" size="100%">Curr Pharm Des</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Curr. Pharm. Des.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Arthritis, Rheumatoid</style></keyword><keyword><style  face="normal" font="default" size="100%">Autoimmune Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunogenetic Phenomena</style></keyword><keyword><style  face="normal" font="default" size="100%">Individualized Medicine</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Pharmacogenetics</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">18</style></volume><pages><style face="normal" font="default" size="100%">5766-75</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Pediatric inflammatory and autoimmune diseases are a wide array of systemic or organ-specific conditions, characterized by an exaggerated immune reactivity, which generally occurs in immunogenetically predisposed children. Among the most important ones, in terms of their diffusion and morbidity in the population worldwide, pediatric inflammatory bowel disease (IBD) and juvenile rheumatoid arthritis (JRA) have to be considered. The aim of personalized therapy is to give to each patient the most appropriate drug and dose regimen, in order to maximize treatment response and reduce the risk of adverse events. In general, several therapeutic options exist for pediatric inflammatory and autoimmune conditions, therefore the perspective of pharmacological tools that allow identification of patients with increased risk of treatment issues related to a particular medication, in terms of lack of efficacy or increased probability of adverse events, is particularly desirable and promising. The present review will be focused on the personalized therapy approaches already available or in development for pediatric patients with IBD or JRA, comprising pharmacokinetic, pharmacodynamic and pharmacogenetic assays.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">35</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22726111?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Franca, Raffaella</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease.</style></title><secondary-title><style face="normal" font="default" size="100%">World J Gastroenterol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">World J. Gastroenterol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Drug Resistance</style></keyword><keyword><style  face="normal" font="default" size="100%">Glucocorticoids</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">P-Glycoproteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Glucocorticoid</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription, Genetic</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Mar 7</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">17</style></volume><pages><style face="normal" font="default" size="100%">1095-108</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn's disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity. However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormone-free GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient's specific genetic background, thus improving on efficacy and safety rates.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21448414?dopt=Abstract</style></custom1></record></records></xml>