Search

Your search keyword '"Franca, Raffaella"' showing total 142 results
Start Over Author "Franca, Raffaella"
142 results on '"Franca, Raffaella"'

5. Impact of mercaptopurine metabolites on disease outcome in the AIEOP‐BFM 2009 protocol for acute lymphoblastic leukemia

Author

Franca, Raffaella, primary, Stocco, Gabriele, additional, Kiren, Valentina, additional, Tessitore, Antimo, additional, Fagioli, Franca, additional, Quarello, Paola, additional, Bertorello, Nicoletta, additional, Rizzari, Carmelo, additional, Colombini, Antonella, additional, Bettini, Laura Rachele, additional, Locatelli, Franco, additional, Vinti, Luciana, additional, Girardi, Katia, additional, Silvestri, Daniela, additional, Valsecchi, Maria Grazia, additional, Decorti, Giuliana, additional, and Rabusin, Marco, additional

Published
2023
Full Text
View/download PDF

6. Impact of Mercaptopurine Metabolites on Disease Outcome in the AIEOP‐BFM ALL 2009 Protocol for Acute Lymphoblastic Leukemia.

Author

Franca, Raffaella, Stocco, Gabriele, Kiren, Valentina, Tessitore, Antimo, Fagioli, Franca, Quarello, Paola, Bertorello, Nicoletta, Rizzari, Carmelo, Colombini, Antonella, Bettini, Laura Rachele, Locatelli, Franco, Vinti, Luciana, Girardi, Katia, Silvestri, Daniela, Valsecchi, Maria Grazia, Decorti, Giuliana, and Rabusin, Marco

Subjects
LYMPHOBLASTIC leukemia, ACUTE leukemia, HIGH performance liquid chromatography, PROPORTIONAL hazards models, LEUCOCYTES, ERYTHROCYTES, SINGLE nucleotide polymorphisms
Abstract

In the maintenance phase of Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)‐ Berlin‐Frankfurt‐Muenster (BFM) acute lymphoblastic leukemia (ALL) 2009 protocol, mercaptopurine (MP) is given at the planned dose of 50 mg/m2/day; however, dose adjustments are routinely performed to target patients' white blood cells to the optimal range of 2,000–3,000 cells/μL. Pediatric patients with ALL (n = 290, age: median (1st–3rd quartile): 4.8 (3.0–8.1) years; boys: 56.9%) were enrolled mainly in 4 medium‐large Italian pediatric hospitals; 14.1% of patients relapsed after a median (1st–3rd quartile) follow‐up time of 4.43 (3.82–5.46) years from maintenance beginning. MP metabolites (thionucleotide (TGN) and methyl‐derivatives (MMPN)) were measured in the erythrocytes of 387 blood samples of 200 patients by high performance liquid chromatography with ultraviolet detection. Single‐nucleotide polymorphisms (SNPs; (rs1800462, rs1800460, and rs1142345 in TPMT gene, rs116855232 in NUDT15, rs1127354, rs7270101, rs6051702 in ITPA, and rs2413739 in PACSIN2) were characterized by Taqman SNP genotyping assays. Cox proportional hazard models did not show an impact of TGN levels and variability on relapse. In contrast, after multivariate analysis, relapse hazard ratio (HR) increased in children with ALL of the intermediate risk arm compared with those in standard risk arm (3.44, 95% confidence interval (CI), 1.31–9.05, P = 0.012), and in carriers of the PACSIN2 rs2413739 T allele compared with those with the CC genotype (heterozygotes CT: HR, 2.32, 95% CI, 0.90–5.97, P = 0.081; and homozygous TT: HR, 4.14, 95% CI, 1.54–11.11, P = 0.005). Future studies are needed to confirm the lack of impact of TGN levels and variability on relapse in the AIEOP‐BFM ALL trials, and to clarify the mechanism of PACSIN2 rs2413739 on outcome. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

10. A Novel ELISA-Based Peptide Biosensor Assay for Screening ABL1 Activity in vitro: A Challenge for Precision Therapy in BCR-ABL1 and BCR-ABL1 Like Leukemias

Author

Montecchini, Oksana, primary, Braidotti, Stefania, additional, Franca, Raffaella, additional, Zudeh, Giulia, additional, Boni, Christian, additional, Sorio, Claudio, additional, Toffoletti, Eleonora, additional, Rabusin, Marco, additional, Tommasini, Alberto, additional, Decorti, Giuliana, additional, and Stocco, Gabriele, additional

Published
2021
Full Text
View/download PDF

17. PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity

Author

Stocco, Gabriele, Yang, Wenjian, Crews, Kristine R., Thierfelder, William E., Decorti, Giuliana, Londero, Margherita, Franca, Raffaella, Rabusin, Marco, Valsecchi, Maria Grazia, Pei, Deqing, Cheng, Cheng, Paugh, Steven W., Ramsey, Laura B., Diouf, Barthelemy, McCorkle, Joseph Robert, Jones, Terreia S., Pui, Ching-Hon, Relling, Mary V., and Evans, William E.

Published
2012
Full Text
View/download PDF

21. Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants

Author

Lucafò, Marianna, primary, Stocco, Gabriele, additional, Martelossi, Stefano, additional, Favretto, Diego, additional, Franca, Raffaella, additional, Malusà, Noelia, additional, Lora, Angela, additional, Bramuzzo, Matteo, additional, Naviglio, Samuele, additional, Cecchin, Erika, additional, Toffoli, Giuseppe, additional, Ventura, Alessandro, additional, and Decorti, Giuliana, additional

Published
2019
Full Text
View/download PDF

25. Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients.

Author

Lucafò, Marianna, Franzin, Martina, Lagatolla, Cristina, Franca, Raffaella, Bramuzzo, Matteo, Stocco, Gabriele, and Decorti, Giuliana

Subjects
GUT microbiome, ANTINEOPLASTIC agents, INFLAMMATORY bowel diseases, JUVENILE idiopathic arthritis, IMMUNOLOGIC diseases, IMMUNOSUPPRESSIVE agents
Abstract

Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute lymphoblastic leukemia (ALL), are pathological conditions affecting the pediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity. Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy. In particular, the effect of intestinal microflora through translocation, immunomodulation, metabolism, enzymatic degradation, and reduction of bacterial diversity seems to be one of the reasons of interindividual variability in the therapeutic response. Although the extent of the role of intestinal microflora in chemotherapy and immunosuppression remains still unresolved, current evidence on bacterial compositional shifts will be taken in consideration together with clinical response to drugs for a better and personalized therapy. This review is focused on the effect of the intestinal microbiota on the efficacy of pharmacological therapy of agents used to treat IBD, JIA, and ALL. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

28. Multicentric Case–Control Study on Azathioprine Dose and Pharmacokinetics in Early-onset Pediatric Inflammatory Bowel Disease

Author

Stocco, Gabriele, primary, Martelossi, Stefano, additional, Arrigo, Serena, additional, Barabino, Arrigo, additional, Aloi, Marina, additional, Martinelli, Massimo, additional, Miele, Erasmo, additional, Knafelz, Daniela, additional, Romano, Claudio, additional, Naviglio, Samuele, additional, Favretto, Diego, additional, Cuzzoni, Eva, additional, Franca, Raffaella, additional, Decorti, Giuliana, additional, and Ventura, Alessandro, additional

Published
2017
Full Text
View/download PDF

29. ITPA genetic polymorphism is possibly associated with survival rate in Korean children with acute lymphoblastic leukemia

Author

STOCCO, GABRIELE, FRANCA, RAFFAELLA, LONDERO, MARGHERITA, DECORTI, GIULIANA, Stocco, Gabriele, Franca, Raffaella, Londero, Margherita, and Decorti, Giuliana

Subjects
pharmacogenomics
Abstract

Comment on "Pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and ITPA polymorphism." Kim H, Kang HJ, Kim HJ, Jang MK, Kim NH, Oh Y, Han BD, Choi JY, Kim CW, Lee JW, et al. PLoS One. 2012; 7(9):e45558. Epub 2012 Sep 24.

Published
2013

30. DMET™ Plus array delivers results in good concordance with those of several lower-throughput genotyping methods in patient samples

Author

STOCCO, GABRIELE, FRANCA, RAFFAELLA, LONDERO, MARGHERITA, DECORTI, GIULIANA, Stocco, Gabriele, Franca, Raffaella, Londero, Margherita, and Decorti, Giuliana

Subjects
Pharmacogenomics
Abstract

Comment on "Concordance of DMET plus genotyping results with those of orthogonal genotyping methods" Fernandez CA, Smith C, Yang W, Lorier R, Crews KR, Kornegay N, Hicks JK, Stewart CF, Kawedia JD, Ramsey LB, et al. Clin Pharmacol Ther. 2012 Sep; 92(3):360-5. Epub 2012 Aug 8.

Published
2013

31. PACSIN2rs2413739 influence on thiopurine pharmacokinetics: validation studies in pediatric patients

Author

Franca, Raffaella, Stocco, Gabriele, Favretto, Diego, Giurici, Nagua, del Rizzo, Irene, Locatelli, Franco, Vinti, Luciana, Biondi, Andrea, Colombini, Antonella, Fagioli, Franca, Barisone, Elena, Pelin, Marco, Martellossi, Stefano, Ventura, Alessandro, Decorti, Giuliana, and Rabusin, Marco

Abstract

The aim of the study was to validate the impact of the single-nucleotide polymorphism rs2413739 (T > C) in the PACSIN2gene on thiopurines pharmacological parameters and clinical response in an Italian cohort of pediatric patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). In ALL, PACSIN2rs2413739 T allele was associated with a significant reduction of TPMT activity in erythrocytes (p= 0.0094, linear mixed-effect model, multivariate analysis considering TPMTgenotype) and increased severe gastrointestinal toxicity during consolidation therapy (p= 0.049). A similar trend was present also for severe hematological toxicity during maintenance. In IBD, no significant effect of rs2413739 could be found on TPMT activity, however azathioprine effectiveness was reduced in patients carrying the T allele (linear mixed effect, p= 0.0058). In PBMC from healthy donors, a positive correlation between PACSIN2 and TPMT protein concentration could be detected (linear mixed effect, p= 0.045). These results support the role of PACSIN2polymorphism on TPMT activity and mercaptopurine adverse effects in patients with ALL. Further evidence on PBMC and pediatric patients with IBD supports an association between PACSIN2 variants, TPMT activity, and thiopurines effects, even if more studies are needed since some of these effects may be tissue specific.

Published
2020
Full Text
View/download PDF

34. Heterodimeric amino acid transporters: glycoprotein domain(s) involved in functional subunit interaction

Author

Franca, Raffaella

Subjects
GLYCOPROTEINS + GLYCOPEPTIDES (BIOCHEMISTRY), AMINOSÄURENTRANSPORT (MEMBRANBIOLOGIE), PIPIDAE (ZOOLOGIE), AMINO ACID TRANSPORT (MEMBRANE BIOLOGY), STRUCTURE-FUNCTION RELATIONSHIP OF BIOMOLECULES, STRUKTUR-FUNKTIONSBEZIEHUNG DER BIOMOLEKÜLE, Life sciences, GLYKOPROTEINE + GLYKOPEPTIDE (BIOCHEMIE), PIPIDAE (ZOOLOGY)
Published
2004
Full Text
View/download PDF

36. Deletion of Glutathione-S-Transferase M1 Reduces Azathioprine Metabolite Concentrations in Young Patients With Inflammatory Bowel Disease

Author

Stocco, Gabriele, primary, Cuzzoni, Eva, additional, De Iudicibus, Sara, additional, Franca, Raffaella, additional, Favretto, Diego, additional, Malusà, Noelia, additional, Londero, Margherita, additional, Cont, Gabriele, additional, Bartoli, Fiora, additional, Martelossi, Stefano, additional, Ventura, Alessandro, additional, and Decorti, Giuliana, additional

Published
2014
Full Text
View/download PDF

44. The ectopic FOF1 ATP synthase of rat liver is modulated in acute cholestasis by the inhibitor protein IF1.

Author

Giorgio, Valentina, Bisetto, Elena, Franca, Raffaella, Harris, David A., Passamonti, Sabina, and Lippe, Giovanna

Subjects
CHOLESTASIS, CELL membranes, PROTEINS, MITOCHONDRIA, LIPOPROTEINS
Abstract

Rat liver plasma membranes contain FOF1 complexes (ecto-FOF1) displaying a similar molecular weight to the mitochondrial FOF1 ATP synthase, as evidenced by Blue Native PAGE. Their ATPase activity was stably reduced in short-term extra-hepatic cholestasis. Immunoblotting and immunoprecipitation analyses demonstrated that the reduction in activity was not due to a decreased expression of ecto-FOF1 complexes, but to an increased level of an inhibitory protein, ecto-IF1, bound to ecto-FOF1. Since cholestasis down regulates the hepatic uptake of HDL-cholesterol, and ecto-FOF1 has been shown to mediate SR-BI-independent hepatic uptake of HDL-cholesterol, these findings provide support to the hypothesis that ecto-FOF1 contributes to the fine control of reverse cholesterol transport, in parallel with SR-BI. No activity change of the mitochondrial FOF1 ATP synthase (m-FOF1), or any variation of its association with m-IF1 was observed in cholestasis, indicating that ecto-IF1 expression level is modulated independently from that of ecto-FOF1, m-IF1 and m-FOF1. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

46. PACSIN2rs2413739 Polymorphism and Thiopurine Pharmacokinetics: Validation Studies in Pediatric Patients

Author

Stocco, Gabriele, Franca, Raffaella, Favretto, Diego, Giurici, Nagua, Ventura, Alessandro, Decorti, Giuliana, Vinti, Luciana, Colombini, Antonella, Brivio, Erica, Bettini, Laura Rachele, Bini, Ilaria, Sismondi, Francesca, Mandese, Alessandra, Malusà, Noelia, Martelossi, Stefano, and Rabusin, Marco

Abstract

Thiopurines such as thioguanine (TG), mercaptopurine (MP) and its prodrug azathioprine (AZA) are key antileukemic and immunosuppressive drugs in the treatment of several pediatric diseases such as acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD): their therapeutic action is affected by the enzyme thiopurine-S-methyltransferase (TPMT) whose encoding gene is polymorphic and whose enzymatic activity is also trans-regulated by the intronic single nucleotide polymorphism (SNP) rs2413739 (T>C) in the PACSIN2gene.

Published
2017
Full Text
View/download PDF

47. The ectopic FOF1 ATP synthase of rat liver is modulated in acute cholestasis by the inhibitor protein IF1.

Author

Giorgio, Valentina, Bisetto, Elena, Franca, Raffaella, Harris, David A., Passamonti, Sabina, and Lippe, Giovanna

Subjects
*CHOLESTASIS, *CELL membranes, *PROTEINS, *MITOCHONDRIA, *LIPOPROTEINS
Abstract

Rat liver plasma membranes contain FOF1 complexes (ecto-FOF1) displaying a similar molecular weight to the mitochondrial FOF1 ATP synthase, as evidenced by Blue Native PAGE. Their ATPase activity was stably reduced in short-term extra-hepatic cholestasis. Immunoblotting and immunoprecipitation analyses demonstrated that the reduction in activity was not due to a decreased expression of ecto-FOF1 complexes, but to an increased level of an inhibitory protein, ecto-IF1, bound to ecto-FOF1. Since cholestasis down regulates the hepatic uptake of HDL-cholesterol, and ecto-FOF1 has been shown to mediate SR-BI-independent hepatic uptake of HDL-cholesterol, these findings provide support to the hypothesis that ecto-FOF1 contributes to the fine control of reverse cholesterol transport, in parallel with SR-BI. No activity change of the mitochondrial FOF1 ATP synthase (m-FOF1), or any variation of its association with m-IF1 was observed in cholestasis, indicating that ecto-IF1 expression level is modulated independently from that of ecto-FOF1, m-IF1 and m-FOF1. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

48. Terapia di precisione per malattie autoimmuni mediate da chinasi: sviluppo di un sistema in vitro per la diagnosi e il monitoraggio clinico

Author

BRAIDOTTI, STEFANIA, Braidotti, Stefania, STOCCO, GABRIELE, and FRANCA, RAFFAELLA

Subjects
AGS, Peptide biosensor, iPSC, JAK inhibitor, precision medicine, Settore BIO/14 - Farmacologia
Abstract

Questo progetto si concentra sulle tirosin chinasi della famiglia JAK e sui suoi inibitori, JAKi, e ha l'obiettivo di sviluppare strumenti in vitro per la personalizzazione nelle malattie oncoematologiche e autoimmuni, come la sindrome di Aicardi-Goutieres (AGS). Il primo tool è un saggio ELISA in vitro basato su biosensori peptidici (PJAK2-L e PJAK2-S) per misurare l'attività aberrante di JAK2. Il secondo invece è la creazione di neuroni derivati da cellule staminali pluripotenti indotte (iPSC) per testare la sicurezza e l'efficacia dei JAKi in modelli paziente-specifici di AGS. Le linee cellulari oncoematologiche (HEL, SET-2 e MHH-CALL-4) caratterizzate da alterazioni genetiche che portano all’attivazione della pathway JAK2-STAT5, hanno mostrato che HEL e SET-2 erano sensibili ai JAKi ruxolitinib, baricitinib, tofacitinib e pacritinib. Abbiamo ottimizzato il protocollo ELISA lavorando prima sulla tirosina chinasi ABL1 come pubblicato (Montecchini, Braidotti et. al, 2021, Front Pharmacol) e applicando poi la metodologia ai peptidi PJAK2-L e PJAK2-S, ma senza successo dal momento che i peptidi non sono stati fosforilati dopo l'incubazione dei lisati ottenuti dalle linee cellulari. Il saggio è stato quindi eseguito sulla chinasi JAK2 immunoprecipitata a partire da lisati della linea HEL; emerge un segnale di fosforilazione rilevante per PJAK2-L rispetto al background (intensità di fluorescenza: HEL lisato, 2510,26±931,01; HEL lisato + PJAK2-L, 87710,99± 3278,33, P 2, 5 μM) ha aumentato la vitalità cellulare in AGS2-iPSC rispetto ai controlli BJ-iPSC ( P 2.5 μM) increased cell viability in AGS2-iPSC compared to controls BJ-iPSC (P

Published
2023

49. PACSIN2 as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells

Author

Giulia Zudeh, Raffaella Franca, Marianna Lucafò, Erik J Bonten, Matteo Bramuzzo, Riccardo Sgarra, Cristina Lagatolla, Martina Franzin, William E Evans, Giuliana Decorti, Gabriele Stocco, Zudeh, Giulia, Franca, Raffaella, Lucafò, Marianna, Bonten, Erik J, Bramuzzo, Matteo, Sgarra, Riccardo, Lagatolla, Cristina, Franzin, Martina, Evans, William E, Decorti, Giuliana, and Stocco, Gabriele

Subjects
pharmacogenomics, personalized therapy, lymphoid cells, autophagy, pediatric patients, pharmacogenomic, Ecology, thiopurines, Health, Toxicology and Mutagenesis, PACSIN2, intestinal cells, Plant Science, TPMT, inflammatory bowel disease, Biochemistry, Genetics and Molecular Biology (miscellaneous), intestinal cell, thiopurine, lymphoid cell, pediatric patient
Abstract

PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve autophagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of inflammatory bowel disease pediatric patients at diagnosis. PACSIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein–protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cytotoxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy.

Published
2023

50. Pharmacogenetics of treatments for inflammatory bowel disease

Author

Raffaella Franca, Giuliana Decorti, Davide Selvestrel, Marianna Lucafò, Gabriele Stocco, Debora Curci, Letizia Pugnetti, Lucafò, Marianna, Franca, Raffaella, Selvestrel, Davide, Curci, Debora, Pugnetti, Letizia, Decorti, Giuliana, and Stocco, Gabriele

Subjects
Genetic Markers, 0301 basic medicine, medicine.medical_specialty, Biologic, Biologics, Toxicology, Clinical decision support system, Inflammatory bowel disease, Epigenesis, Genetic, Dose-Response Relationship, 03 medical and health sciences, 0302 clinical medicine, Genetic, Gastrointestinal Agents, Maintenance therapy, inflammatory bowel disease, thalidomide, thiopurine, Gastrointestinal Agent, Genetic Marker, medicine, Humans, Genetic Predisposition to Disease, Dosing, Intensive care medicine, Adverse effect, Pharmacology, Gastrointestinal agent, glucocorticoids, Dose-Response Relationship, Drug, thiopurines, business.industry, Pharmacogenetic, Inflammatory Bowel Disease, General Medicine, pharmacogenetics, Inflammatory Bowel Diseases, Pharmacogenetics, medicine.disease, Thalidomide, 030104 developmental biology, glucocorticoid, 030211 gastroenterology & hepatology, Drug, business, Epigenesis, Human, medicine.drug
Abstract

INTRODUCTION 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.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results