|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease:Effect of N-acetyl transferase polymorphisms显示文摘AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate(5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase(NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides(TGN) and methymercaptopurine nucleotides(MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients(3 females and 9 males, median age 16 years) with inflammatory bowel disease(6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines(7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase(ITPA) and thiopurine methyl transferase(TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 108 erythrocytes(range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations(absolutemean reduction 109 pmol/8 × 108 erythrocytes) was observed(median 221 pmol/8 × 108 erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration(P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study. | Gabriele Stocco Eva Cuzzoni Sara De Iudicibus Diego Favretto Noelia Malusà Stefano Martelossi Elena Pozzi Paolo Lionetti Alessandro Ventura Giuliana Decorti | 2015 | World Journal of Gastroenterology2015，21，12： | 5 |
| 2 | Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events显示文摘Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine. | Elena Genova Federica Cavion Marianna Lucafò Luigina De Leo Marco Pelin Gabriele Stocco Giuliana Decorti | 2019 | World Journal of Stem Cells2019，11，12： | 4 |
| 3 | Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?显示文摘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.reserved. | Gabriele Stocco Marco Pelin Raffaella Franca Sara De Iudicibus Eva Cuzzoni Diego Favretto Stefano Martelossi Alessandro Ventura Giuliana Decorti | 2014 | World Journal of Gastroenterology2014，20，13： | 2 |
| 4 | StAR PROTEIN AND THE REGULATION OF STEROID HORMONE BIOSYNTHESIS显示文摘 | Douglas M Stocco | 2001 | Annual Review of Physiology2001，，： | 2 |
| 5 | Dimethoate inhibits steroidogenesis by disrupting transcription of the steroidogenic acute regulatory (STAR) gene 显示文摘 | Walsh LP Webster DR Stocco DM | 2000 | J Endocrinol2000，167，： | 1 |
| 6 | Multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression:more complicated than we thought显示文摘 | Stocco DM Wang X Jo Y | 2005 | Mol Endocrinol2005，19，11： | 1 |
| 7 | Steroidogenic acute regulatory protein: The StAR still shines brightly显示文摘 | Clark B J Stocco D M | 1997 | Mol Cell Endocrinol1997，134，： | 1 |
| 8 | Inflammatory bowel disease显示文摘 | Gabriele Stocco Giuliana Decorti Fiora Bartoli Stefano Martelossi Alessandro Ventura | 2007 | The Lancet . 2007 (9584)2007，，9584： | 1 |
| 9 | Tracking the role of a star in the sky of the new millennium 显示文摘 | Stocco DM | 2001 | Mol Endocrinol2001，15，8： | 1 |
| 10 | Involvement of multiple transcription factors in the regulation of steroidogenic acute regulatory protein gene expression 显示文摘 | Manna PR Wang XJ Stocco DM | 2003 | Steroids2003，68，14： | 1 |
| 11 | A StAR search: implications in controlling steroidogenesis显示文摘 | Stocco D M | 1997 | Biol Reprod1997，56，： | 1 |
| 12 | The molecular control of corpus luteum formation, function, and regression显示文摘 | Stocco C Telleria C Gibori G | 2007 | Endocr Rev2007，28，1： | 1 |
| 13 | Identification of regulatory elements in the Cypl9 proximal promoter in rat luteal cells 显示文摘 | Stocco C Kwintkiewicz J Cai Z | 2007 | Mol Endocrinol2007，39，4： | 1 |
| 14 | Elements involved in the regulation of the StAR genes显示文摘 | STOCCO D M CLARK B J REINHART A J | 2001 | Molecular and Cellular Endocrinology2001，177，12： | 1 |
| 15 | Down-regulation of steroidogenic acute regulatory (StAR) protein in rat Leydig cells: implications for regulation of testosterone production during aging显示文摘 | Leers-Sucheta S Stocco DM Azhar S | 1999 | Mech Ageing Dev1999，107，2： | 1 |
| 16 | Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH,prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats显示文摘 | Weber KS Setchell KD Stocco DM | 2001 | J Endocrinol2001，170，3： | 1 |
| 17 | Multilocus genotypes of relevance for drug metabolizing enzymes and therapy with thiopurines in patients with acute lymphoblastic leukemia 显示文摘 | Stocco G Franca R Verzeguassi F | 2012 | Front Genet2012，3，： | 1 |
| 18 | StAR protein and the regulation of steroid hormone biosynthesis 显示文摘 | Stocco D M | 2001 | Annual Rev Physiol2001，63，： | 1 |
| 19 | Assessment of the role of activator protein-1 on transcription of the mouse steroidogenic acute regulatory protein gene显示文摘 | Manna PR Eubank DW Stocco DM | 2004 | Mol Endocrinol2004，18，3： | 1 |
| 20 | Stimulatory effect of progesterone on the expression of steroidogenic acute regulatory protein in MA-10 Leydig cells显示文摘 | Schwarzenbach H Manna P R Stocco D M | 2003 | Biology of Reproduction2003，68，3： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员