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Book ; Online: Pharmacogenomics and Personalized Medicine

Cecchin, Erika / Stocco, Gabriele

2020

Keywords	Medicine ; CYP2C9 ; VKORC1 ; warfarin ; warfarin initiation phase of therapy ; INR ; pharmacogenetics study ; pharmacogenomics ; pharmacogenetics ; genotype ; phenotype ; alleles ; precision medicine ; pharmacotranscriptomics ; high-throughput analysis ; childhood acute lymphoblastic leukemia ; clopidogrel ; acenocoumarol ; CDSS ; implementation ; azathioprine ; inflammatory bowel disease ; glutathione-S transferase ; pharmacokinetics ; nucleoside analogs ; microRNAs ; gene expression ; drug resistance ; AML ; cisplatin ; nephrotoxicity ; kidney injury ; genetic polymorphisms ; pre-emptive ; panel ; breast cancer subtype ; miRNA ; pathway ; crosstalk network ; precision drugs ; ovarian cancer ; platinum resistance ; focal copy number alterations ; whole exome sequencing ; personalized medicine ; human genetics ; pharmacology
Size	1 electronic resource (208 pages)
Publisher	MDPI - Multidisciplinary Digital Publishing Institute
Publishing place	Basel, Switzerland
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021044075
ISBN	9783039367313 ; 3039367315
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Perspectives on Rational Drug Design and Therapy for Pediatric Precision Medicine.

Stocco, Gabriele

Current medicinal chemistry

2018 Volume 25, Issue 24, Page(s) 2762–2763

MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Autoimmune Diseases/therapy ; Biological Products/therapeutic use ; Child ; Drug Design ; Humans ; Inflammatory Bowel Diseases/therapy ; Precision Medicine
Chemical Substances	Antibodies, Monoclonal ; Biological Products
Language	English
Publishing date	2018-07-17
Publishing country	United Arab Emirates
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/092986732524180704125041
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Article ; Online: Decrease in Mycophenolate Mofetil Plasma Concentration in the Presence of Antibiotics: A Case Report in a Cystic Fibrosis Patient with Lung Transplant.

Ponis, Giuliano / Decorti, Giuliana / Barbi, Egidio / Stocco, Gabriele / Maschio, Massimo

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising ... ...

Abstract	Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug-drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.
MeSH term(s)	Humans ; Middle Aged ; Mycophenolic Acid/therapeutic use ; Mycophenolic Acid/pharmacology ; Cystic Fibrosis/complications ; Cystic Fibrosis/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Immunosuppressive Agents/adverse effects ; Lung Transplantation ; Enzyme Inhibitors
Chemical Substances	Mycophenolic Acid (HU9DX48N0T) ; Anti-Bacterial Agents ; Immunosuppressive Agents ; Enzyme Inhibitors
Language	English
Publishing date	2024-02-17
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042358
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Challenges in Therapeutic Drug Monitoring: Optimizing Biological Treatments in Patients With Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases.

Papamichael, Konstantinos / Stocco, Gabriele / Ruiz Del Agua, Ainhoa

Therapeutic drug monitoring

2023 Volume 45, Issue 5, Page(s) 579–590

Abstract: Background: Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and ...

Abstract	Background: Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective. Methods: This narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review. Results: Proactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti-tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times. Conclusions: Despite several knowledge gaps regarding proactive TDM of anti-tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future.
MeSH term(s)	Humans ; Child ; Infliximab/therapeutic use ; Adalimumab/therapeutic use ; Drug Monitoring ; Inflammatory Bowel Diseases/drug therapy ; Necrosis/chemically induced ; Necrosis/drug therapy ; Gastrointestinal Agents/therapeutic use
Chemical Substances	Infliximab (B72HH48FLU) ; Adalimumab (FYS6T7F842) ; Gastrointestinal Agents
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0000000000001095
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Article ; Online: Pharmacogenomics and Personalized Medicine.

Cecchin, Erika / Stocco, Gabriele

Genes

2020 Volume 11, Issue 6

Abstract: Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, ...

Abstract	Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including the study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of the inter-individual variability in drug metabolism. In this Special Issue, we collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastractures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.
MeSH term(s)	Biomarkers ; Humans ; Pharmacogenetics ; Pharmacogenomic Testing ; Precision Medicine
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-06-22
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes11060679
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Article ; Online: Biomarkers for gastrointestinal adverse events related to thiopurine therapy.

Zudeh, Giulia / Franca, Raffaella / Stocco, Gabriele / Decorti, Giuliana

World journal of gastroenterology

2021 Volume 27, Issue 38, Page(s) 6348–6356

Abstract: Thiopurines are immunomodulators used in the treatment of acute lymphoblastic leukemia and inflammatory bowel diseases. Adverse reactions to these agents are one of the main causes of treatment discontinuation or interruption. Myelosuppression is the ... ...

Abstract	Thiopurines are immunomodulators used in the treatment of acute lymphoblastic leukemia and inflammatory bowel diseases. Adverse reactions to these agents are one of the main causes of treatment discontinuation or interruption. Myelosuppression is the most frequent adverse effect; however, approximately 5%-20% of patients develop gastrointestinal toxicity. The identification of biomarkers able to prevent and/or monitor these adverse reactions would be useful for clinicians for the proactive management of long-term thiopurine therapy. In this editorial, we discuss evidence supporting the use of
MeSH term(s)	Azathioprine/adverse effects ; Biomarkers ; Humans ; Immunologic Factors ; Mercaptopurine/adverse effects ; Methyltransferases/genetics ; Pyrophosphatases
Chemical Substances	Biomarkers ; Immunologic Factors ; Mercaptopurine (E7WED276I5) ; Methyltransferases (EC 2.1.1.-) ; Pyrophosphatases (EC 3.6.1.-) ; Azathioprine (MRK240IY2L)
Language	English
Publishing date	2021-02-28
Publishing country	United States
Document type	Editorial
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v27.i38.6348
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Article ; Online: Expression profiles of the lncRNA antisense GAS5-AS1 in colon biopsies from pediatric inflammatory bowel disease patients and its role in regulating sense transcript GAS5.

Curci, Debora / Franzin, Martina / Zudeh, Giulia / Bramuzzo, Matteo / Lega, Sara / Decorti, Giuliana / Stocco, Gabriele / Lucafò, Marianna

European journal of pediatrics

2024 Volume 183, Issue 4, Page(s) 1657–1665

Abstract: The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this ... ...

Abstract	The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this study aims to detect whether GAS5-AS1 and GAS5 levels are related to IBD clinical parameters and investigate their correlation in vitro. Twenty-six IBD pediatric patients were enrolled; paired inflamed and non-inflamed intestinal biopsies were collected. We evaluated GAS5 and GAS5-AS1 levels by real-time PCR. The role of GAS5 and GAS5-AS1 was assessed in vitro by transient silencing in THP1-derived macrophages. GAS5-AS1 and GAS5 levels were associated with patients' clinical parameters; GAS5-AS1 expression was downregulated in inflamed tissues and inversely correlated with disease activity. A positive correlation between GAS5-AS1 and GAS5 levels was observed in non-inflamed biopsies. On THP1-derived macrophages, a reduced amount of both GAS5-AS1 and GAS5 was observed; accordingly, matrix metalloproteinase (MMP) 9 was increased. After GAS5-AS1 silencing, a downregulation of GAS5 was found, whereas no effect was detected on GAS5-AS1 after GAS5 silencing. Conclusion: This study provided for the first time new insights into the potential role of GAS5-AS1 in IBD. GAS5-AS1 modulates GAS5 levels in vitro and may serve as a potential IBD diagnostic biomarker. What is Known: • GAS5 is involved in regulating intestinal MMP-2 and MMP-9 in pediatric patients with IBD; • GAS5-AS1 has never been investigated in the context of IBD; • GAS5-AS1 regulates the expression of GAS5, increasing its stability in tissues and in vitro cell models of cancer. What is New: • GAS5-AS1 correlated with GAS5 and IBD clinical parameters; • GAS5-AS1 can modulate GAS5 levels in macrophages; • GAS5-AS1 may serve as potential IBD diagnostic biomarker.
MeSH term(s)	Humans ; Child ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/genetics ; Biopsy ; Biomarkers ; Colon/metabolism
Chemical Substances	RNA, Long Noncoding ; Biomarkers
Language	English
Publishing date	2024-01-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	194196-3
ISSN	1432-1076 ; 0340-6199 ; 0943-9676
ISSN (online)	1432-1076
ISSN	0340-6199 ; 0943-9676
DOI	10.1007/s00431-023-05403-4
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Article ; Online: iPSCs as a groundbreaking tool for the study of adverse drug reactions: A new avenue for personalized therapy.

Rispoli, Paola / Scandiuzzi Piovesan, Tatiana / Decorti, Giuliana / Stocco, Gabriele / Lucafò, Marianna

WIREs mechanisms of disease

2023 Volume 16, Issue 1, Page(s) e1630

Abstract: Induced pluripotent stem cells (iPSCs), obtained by reprogramming different somatic cell types, represent a promising tool for the study of drug toxicities, especially in the context of personalized medicine. Indeed, these cells retain the same genetic ... ...

Abstract	Induced pluripotent stem cells (iPSCs), obtained by reprogramming different somatic cell types, represent a promising tool for the study of drug toxicities, especially in the context of personalized medicine. Indeed, these cells retain the same genetic heritage of the donor, allowing the development of personalized models. In addition, they represent a useful tool for the study of adverse drug reactions (ADRs) in special populations, such as pediatric patients, which are often poorly represented in clinical trials due to ethical issues. Particularly, iPSCs can be differentiated into any tissue of the human body, following several protocols which use different stimuli to induce specific differentiation processes. Differentiated cells also maintain the genetic heritage of the donor, and therefore are suitable for personalized pharmacological studies; moreover, iPSC-derived differentiated cells are a valuable tool for the investigation of the mechanisms underlying the physiological differentiation processes. iPSCs-derived organoids represent another important tool for the study of ADRs. Precisely, organoids are in vitro 3D models which better represent the native organ, both from a structural and a functional point of view. Moreover, in the same way as iPSC-derived 2D models, iPSC-derived organoids are appropriate personalized models since they retain the genetic heritage of the donor. In comparison to other in vitro models, iPSC-derived organoids present advantages in terms of versatility, patient-specificity, and ethical issues. This review aims to provide an updated report of the employment of iPSCs, and 2D and 3D models derived from these, for the study of ADRs. This article is categorized under: Cancer > Stem Cells and Development.
MeSH term(s)	Humans ; Child ; Induced Pluripotent Stem Cells ; Cell Differentiation ; Organoids
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2692-9368
ISSN (online)	2692-9368
DOI	10.1002/wsbm.1630
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Article ; Online: Commentary.

Stocco, Gabriele

Clinical chemistry

2013 Volume 59, Issue 7, Page(s) 1027

MeSH term(s)	Azathioprine/therapeutic use ; Colitis, Ulcerative/drug therapy ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Mercaptopurine/therapeutic use
Chemical Substances	Immunosuppressive Agents ; Mercaptopurine (E7WED276I5) ; Azathioprine (MRK240IY2L)
Language	English
Publishing date	2013-06-25
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2012.200428
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Article ; Online: Quantification of 108 illicit drugs and metabolites in bile matrix by LC-MS/MS for the toxicological testing of sudden death cases.

Franzin, Martina / Ruoso, Rachele / Peruch, Michela / Stocco, Gabriele / D'Errico, Stefano / Addobbati, Riccardo

Archives of toxicology

2023 Volume 98, Issue 1, Page(s) 135–149

Abstract: Sudden death could occur after assumption of illicit drugs for recreational purposes in adults or after intoxication in children, and toxicological testing would help identify the cause of the death. Analytical methods sensitive and specific for the ... ...

Abstract	Sudden death could occur after assumption of illicit drugs for recreational purposes in adults or after intoxication in children, and toxicological testing would help identify the cause of the death. Analytical methods sensitive and specific for the quantification of a great number of drugs and metabolites in at least 2 matrices should be used. Bile, collected postmortem, may be considered a specimen alternative to blood and urine to perform toxicological testing because of its extended detection window. The present study proposed a LC-MS/MS method to quantify 108 drugs and metabolites in bile. Compounds belonging to the drugs of abuse classes of amphetamines, benzodiazepines, cocaine derivatives, barbiturates, opioids, z-drugs, and psychedelics were analyzed. The sample preparation is simple and does not require solid-phase extraction. The proposed method showed an appropriate selectivity, specificity, accuracy, and precision of the calibrators and quality controls tested (precision < 15%; accuracy < 100 ± 15%). The sensitivity allowed to identify low amounts of drugs (e.g., morphine limit of detection = 0.2 µg/L; limit of quantification = 1.1 µg/L). There is no significant matrix effect, except for buprenorphine and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol. Carry-over was not present. Analytes were stable at least for 1 month at - 20 °C. Analyzing 13 postmortem specimens, methadone (50%), and cocaine (37.5%) resulted to be the most prevalent consumed substances; the concentrations quantified in bile resulted to be higher than the ones in blood suggesting bile as a potential new matrix for identifying illicit drugs and their metabolites.
MeSH term(s)	Adult ; Humans ; Child ; Chromatography, Liquid/methods ; Liquid Chromatography-Mass Spectrometry ; Bile ; Tandem Mass Spectrometry/methods ; Illicit Drugs ; Substance Abuse Detection/methods ; Cocaine ; Forensic Toxicology/methods
Chemical Substances	Illicit Drugs ; Cocaine (I5Y540LHVR)
Language	English
Publishing date	2023-12-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03631-z
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