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| 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 | Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with crohn's disease显示文摘Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders. | Andrea Taddio Alberto Tommasini Erica Valencic Ettore Biagi Giuliana Decorti Sara De Iudicibus Eva Cuzzoni Giuseppe Gaipa Raffaela Badolato Alberto Prandini Andrea Biondi Alessandro Ventura | 2015 | World Journal of Gastroenterology2015，21，14： | 2 |
| 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 | Evidence for genomic changes in transgenic rice (Oryza sativa L.) recovered from protoplasts显示文摘 | Phan Huy Bao Simona Granata Stefano Castiglione Gejiao Wang Chiara Giordani Elena Cuzzoni Giuseppe Damiani Claudio Bandi Swapan K. Datta Karabi Datta Ingo Potrykus Anna Callegarin Francesco Sala | 1996 | Transgenic Research1996，，2： | 1 |
| 5 | Association between BclI polymorphism in the NR3C1 gene and ( in vitro) individual variations in lymphocyte responses to methylprednisolane 显示文摘 | Cuzzoni E De Iudicibus S Bartoli F | 2012 | Br J Clin Pharmacol2012，73，： | 1 |
| 6 | First-linechemo therapy with vinorelbine, gemcitabine, and carboplatin in the treatmentof brain metastas esfrom non-small·-celllung can cer: a phase IIstudy显示文摘 | Bernardo G Cuzzoni Q Strada M R | 2002 | CancerInvest2002，20，3： | 1 |
| 7 | First-line chemotherapy with vinorelbine, gemcitabine, and carhoplatin in the treatment of brain matastases from non-small-cell lung cancer: a phase Ⅱ study 显示文摘 | Bernardo G Cuzzoni Q Strada MR | 2002 | Cancer Invest2002，20，3： | 1 |
| 8 | First-line chemotherapy with vinorelbine, gemcitabine and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: a phase Ⅱ study 显示文摘 | Bemardo G Cuzzoni Q Strada MR | 2002 | Cancer Invest2002，20，3： | 1 |
| 9 | Molecular analysis of the genome of transgenic rice(Oryza sati- va L)plant produced via particle bombardments or in- tact cell dectroporatlo显示文摘 | Arrecibia A Gentinetta E Cuzzoni E | 1998 | Molecular Breeding1998，4，： | 1 |
| 10 | First-line chemotherapy with vinorelbine,gemcitabine,and carboplatin in the treatment of brain metastases from non-Small cell lung cancer:a phase Ⅱ study显示文摘 | Bemardo G Cuzzoni Q Strada MR | 2002 | Cancer Invest2002，20，3： | 1 |
| 11 | Decreased release of the angiogenic peptide vascular endothelial growth factor in Alzheimer's disease:recovering effect with insulin and DHEA sulfate显示文摘 | Solerte SB Ferrari E Cuzzoni G | 2005 | Dement Geriatr Cogn Disord2005，19，1： | 1 |
| 12 | First-line chemotherapy with vinorelbine,gemcitabine,and carboplatin in the treatment of brain metastases from non-small-cell lung cancer:a phase II study显示文摘 | Bernardo G Cuzzoni Q Strada MR | 2002 | Cancer Invest2002，20，3： | 1 |
| 13 | First-line chemotherapy with vinorelbine,gemcitabine,and carboplatin in the trearment of brain metastases from non-small-cell lung cancer:a phaseⅡstudy显示文摘 | Bernardo G Cuzzoni Q S trada MR | | 0，，03： | 1 |
| 14 | First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: a phase II study 显示文摘 | Bernardo G Cuzzoni Q | 2002 | Cancer Invest2002，20，3： | 1 |
| 15 | First-line chemotherapy with vinorelbine, gemeitabine, and carboplatin in the treatment of brain metas- tases from non-small-cell lung cancer: a phase II study 显示文摘 | Bernardo G Cuzzoni Q Strada MR | 2002 | Cancer in- vest2002，20，3： | 1 |
| 16 | Firist-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain matastases from non-small-cell lung cancer: a phase Ⅱstudy 显示文摘 | Cuzzoni Q Strada MR | 2002 | Cancer Investigation2002，20，3： | 1 |
| 17 | Firist-lin chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain mataatasea from non-small-cell lung cancer: A phaseⅡ study显示文摘 | Bernardo G Cuzzoni Q Strada MR | 2002 | Cancer Investigation2002，20，3： | 1 |
| 18 | Influence of water activity and reaction temperature of ribose-lysine and glucose -lysine Millard systems on mutagenicity,absorbance and content of furfurals显示文摘 | Cuzzoni M T Stoppini G Gazzani G | 1988 | Food Chem Toxicol1988，26，10： | 1 |
| 19 | Dele- tion of glutathione-S-transferase M1 reduces aza- thioprine metabolite concentrations in young pa- tients with inflammatory bowel disease显示文摘 | Stocco G Cuzzoni E De Iudicibus S | 2014 | J Clin Gastroenterol2014，48，1： | 1 |
| 20 | Fate of lymphocytes after withdrawal of tofacitinib treatment显示文摘 | Piscianz E Valencic E Cuzzoni E | 2014 | PLoS One2014，9，1： | 1 |
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