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  1. Article ; Online: Reply to: Temporary Like Achilles: Pre-emptive germline pharmacogenetic testing.

    Guchelaar, Henk-Jan / Swen, Jesse

    Basic & clinical pharmacology & toxicology

    2023  Volume 133, Issue 4, Page(s) 400–401

    MeSH term(s) Pharmacogenomic Testing ; Pharmacogenetics ; Germ Cells
    Language English
    Publishing date 2023-08-24
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2134679-3
    ISSN 1742-7843 ; 1742-7835
    ISSN (online) 1742-7843
    ISSN 1742-7835
    DOI 10.1111/bcpt.13934
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immunogenicity of Monoclonal Antibodies and the Potential Use of HLA Haplotypes to Predict Vulnerable Patients.

    Mosch, Romy / Guchelaar, Henk-Jan

    Frontiers in immunology

    2022  Volume 13, Page(s) 885672

    Abstract: The use of monoclonal antibodies (mAbs) in the clinic has successfully expanded to treatment of cancer, viral infections, inflammations, and other indications. However, some of the classes of mAbs that are used in the clinic show the formation of anti- ... ...

    Abstract The use of monoclonal antibodies (mAbs) in the clinic has successfully expanded to treatment of cancer, viral infections, inflammations, and other indications. However, some of the classes of mAbs that are used in the clinic show the formation of anti-drug antibodies (ADAs) leading to loss of efficacy. This review describes ADA formation for the various mAbs, and its clinical effect. Lastly, this review considers the use of HLA-haplotypes as biomarkers to predict vulnerability of patients sensitive to formation of ADAs.
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological ; Haplotypes ; Humans ; Neoplasms/drug therapy
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents, Immunological
    Language English
    Publishing date 2022-06-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.885672
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Potential Application of Extracellular Vesicles from Liquid Biopsies for Determination of Pharmacogene Expression.

    Habtemariam, Henok D / Guchelaar, Henk-Jan

    Pharmaceuticals (Basel, Switzerland)

    2022  Volume 15, Issue 2

    Abstract: Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or ... ...

    Abstract Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or signaling pathways). Individualizing drug therapy taking into account the genetic profile of the patient has the potential to make drug therapy safer and more effective. Currently, this approach relies on the determination of genetic variants in pharmacogenes by genotyping. However, it is widely acknowledged that large variability in gene expression is attributed to non-structural genetic variants. Therefore, at least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. Extracellular vesicles (EVs) are lipid encapsulated structures that contain cargo such as lipids, nucleic acids and proteins. Since their cargo is tissue- and cell-specific they can be used to determine the expression of pharmacogenes in the liver. In this review, we describe methods of EV isolation and the potential of EVs isolated from liquid biopsies as a tool to determine the expression of pharmacogenes for use in personalized medicine.
    Language English
    Publishing date 2022-02-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15020252
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Pharmacogenomics, a novel section in the European Journal of Human Genetics.

    Guchelaar, Henk-Jan

    European journal of human genetics : EJHG

    2018  Volume 26, Issue 10, Page(s) 1399–1400

    MeSH term(s) Human Genetics/trends ; Humans ; Peer Review, Research/trends ; Pharmacogenetics/trends
    Language English
    Publishing date 2018-07-02
    Publishing country England
    Document type Editorial
    ZDB-ID 1141470-4
    ISSN 1476-5438 ; 1018-4813
    ISSN (online) 1476-5438
    ISSN 1018-4813
    DOI 10.1038/s41431-018-0205-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Personalizing tamoxifen therapy in adjuvant therapy: a brief summary of the ongoing discussion.

    Sanchez-Spitman, Anabel / Guchelaar, Henk-Jan

    Expert review of clinical pharmacology

    2022  Volume 16, Issue 2, Page(s) 93–95

    MeSH term(s) Humans ; Female ; Tamoxifen/pharmacology ; Tamoxifen/therapeutic use ; Antineoplastic Agents, Hormonal/pharmacology ; Antineoplastic Agents, Hormonal/therapeutic use ; Longitudinal Studies ; Breast Neoplasms/drug therapy ; Cytochrome P-450 CYP2D6/genetics ; Genotype
    Chemical Substances Tamoxifen (094ZI81Y45) ; Antineoplastic Agents, Hormonal ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1)
    Language English
    Publishing date 2022-12-06
    Publishing country England
    Document type Editorial ; Comment
    ISSN 1751-2441
    ISSN (online) 1751-2441
    DOI 10.1080/17512433.2023.2154652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Validation of transcriptome signature reversion for drug repurposing in oncology.

    Koudijs, Karel K M / Böhringer, Stefan / Guchelaar, Henk-Jan

    Briefings in bioinformatics

    2022  Volume 24, Issue 1

    Abstract: Transcriptome signature reversion (TSR) has been extensively proposed and used to discover new indications for existing drugs (i.e. drug repositioning, drug repurposing) for various cancer types. TSR relies on the assumption that a drug that can revert ... ...

    Abstract Transcriptome signature reversion (TSR) has been extensively proposed and used to discover new indications for existing drugs (i.e. drug repositioning, drug repurposing) for various cancer types. TSR relies on the assumption that a drug that can revert gene expression changes induced by a disease back to original, i.e. healthy, levels is likely to be therapeutically active in treating the disease. Here, we aimed to validate the concept of TSR using the PRISM repurposing data set, which is-as of writing-the largest pharmacogenomic data set. The predictive utility of the TSR approach as it has currently been used appears to be much lower than previously reported and is completely nullified after the drug gene expression signatures are adjusted for the general anti-proliferative downstream effects of drug-induced decreased cell viability. Therefore, TSR mainly relies on generic anti-proliferative drug effects rather than on targeting cancer pathways specifically upregulated in tumor types.
    MeSH term(s) Humans ; Transcriptome ; Drug Repositioning ; Gene Expression Profiling ; Neoplasms/drug therapy ; Neoplasms/genetics ; Medical Oncology
    Language English
    Publishing date 2022-12-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbac490
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Assay performance and stability of uracil and dihydrouracil in clinical practice

    Knikman, Jonathan E. / Rosing, Hilde / Guchelaar, Henk-Jan / Cats, Annemieke / Beijnen, Jos H.

    Cancer Chemother Pharmacol. 2023 Mar., v. 91, no. 3, p. 257-266

    2023  , Page(s) 257–266

    Abstract: PURPOSE: Measurement of endogenous uracil (U) is increasingly being used as a dose-individualization method in the treatment of cancer patients with fluoropyrimidines. However, instability at room temperature (RT) and improper sample handling may cause ... ...

    Abstract PURPOSE: Measurement of endogenous uracil (U) is increasingly being used as a dose-individualization method in the treatment of cancer patients with fluoropyrimidines. However, instability at room temperature (RT) and improper sample handling may cause falsely increased U levels. Therefore we aimed to study the stability of U and dihydrouracil (DHU) to ensure proper handling conditions. METHODS: Stability of U and DHU in whole blood, serum, and plasma at RT (up to 24 h) and long-term stability (≥ 7 days) at − 20 °C were studied in samples from 6 healthy individuals. U and DHU levels of patients were compared using standard serum tubes (SSTs) and rapid serum tubes (RSTs). The performance of our validated UPLC-MS/MS assay was assessed over a period of 7 months. RESULTS: U and DHU levels significantly increased at RT in whole blood and serum after blood sampling with increases of 12.7 and 47.6% after 2 h, respectively. A significant difference (p = 0.0036) in U and DHU levels in serum was found between SSTs and RSTs. U and DHU were stable at − 20 °C at least 2 months in serum and 3 weeks in plasma. Assay performance assessment fulfilled the acceptance criteria for system suitability, calibration standards, and quality controls. CONCLUSION: A maximum of 1 h at RT between sampling and processing is recommended to ensure reliable U and DHU results. Assay performance tests showed that our UPLC-MS/MS method was robust and reliable. Additionally, we provided a guideline for proper sample handling, processing and reliable quantification of U and DHU.
    Keywords ambient temperature ; blood serum ; calibration ; guidelines ; uracil
    Language English
    Dates of publication 2023-03
    Size p. 257-266
    Publishing place Springer Berlin Heidelberg
    Document type Article ; Online
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-023-04518-7
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: 3D Printing of Pediatric Medication: The End of Bad Tasting Oral Liquids?-A Scoping Review.

    Lafeber, Iris / Ruijgrok, Elisabeth J / Guchelaar, Henk-Jan / Schimmel, Kirsten J M

    Pharmaceutics

    2022  Volume 14, Issue 2

    Abstract: 3D printing of pediatric-centered drug formulations can provide suitable alternatives to current treatment options, though further research is still warranted for successful clinical implementation of these innovative drug products. Extensive research ... ...

    Abstract 3D printing of pediatric-centered drug formulations can provide suitable alternatives to current treatment options, though further research is still warranted for successful clinical implementation of these innovative drug products. Extensive research has been conducted on the compliance of 3D-printed drug products to a pediatric quality target product profile. The 3D-printed tablets were of particular interest in providing superior dosing and release profile similarity compared to conventional drug manipulation and compounding methods, such as oral liquids. In the future, acceptance of 3D-printed tablets in the pediatric patient population might be better than current treatments due to improved palatability. Further research should focus on expanding clinical knowledge, providing regulatory guidance and expansion of the product range, including dosage form possibilities. Moreover, it should enable the use of diverse good manufacturing practice (GMP)-ready 3D printing techniques for the production of various drug products for the pediatric patient population.
    Language English
    Publishing date 2022-02-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics14020416
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Precision Medicine Using Pharmacogenomic Panel-Testing: Current Status and Future Perspectives.

    van der Wouden, Cathelijne H / Guchelaar, Henk-Jan / Swen, Jesse J

    Clinics in laboratory medicine

    2022  Volume 42, Issue 4, Page(s) 587–602

    MeSH term(s) Precision Medicine ; Pharmacogenetics
    Language English
    Publishing date 2022-11-11
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 604580-7
    ISSN 1557-9832 ; 0272-2712
    ISSN (online) 1557-9832
    ISSN 0272-2712
    DOI 10.1016/j.cll.2022.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Personalized Chronomodulated 5-Fluorouracil Treatment: A Physiologically-Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy.

    Marok, Fatima Zahra / Wojtyniak, Jan-Georg / Selzer, Dominik / Dallmann, Robert / Swen, Jesse J / Guchelaar, Henk-Jan / Schwab, Matthias / Lehr, Thorsten

    Clinical pharmacology and therapeutics

    2024  

    Abstract: The discovery of circadian clock genes greatly amplified the study of diurnal variations impacting cancer therapy, transforming it into a rapidly growing field of research. Especially, use of chronomodulated treatment with 5-fluorouracil (5-FU) has ... ...

    Abstract The discovery of circadian clock genes greatly amplified the study of diurnal variations impacting cancer therapy, transforming it into a rapidly growing field of research. Especially, use of chronomodulated treatment with 5-fluorouracil (5-FU) has gained significance. Studies indicate high interindividual variability (IIV) in diurnal variations in dihydropyrimidine dehydrogenase (DPD) activity - a key enzyme for 5-FU metabolism. However, the influence of individual DPD chronotypes on chronomodulated therapy remains unclear and warrants further investigation. To optimize precision dosing of chronomodulated 5-FU, this study aims to: (i) build physiologically-based pharmacokinetic (PBPK) models for 5-FU, uracil, and their metabolites, (ii) assess the impact of diurnal variation on DPD activity, (iii) estimate individual DPD chronotypes, and (iv) personalize chronomodulated 5-FU infusion rates based on a patient's DPD chronotype. Whole-body PBPK models were developed with PK-Sim
    Language English
    Publishing date 2024-01-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.3181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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