Objective: Fluoropyrimidine treatment can be optimized based on dihydropyrimidine dehydrogenase (DPD) activity. DPD dysfunction leads to increased exposure to active metabolites, which can result in severe or even fatal toxicity.
Methods: We provide an overview of 8 years of DPD diagnostic testing (n = 1194).
Results: Within the study period, our diagnostic test evolved from a single-enzyme measurement using first a radiochemical and then a nonradiochemical assay by ultra HPLC-MS in peripheral blood mononuclear cells with uracil, to a combined enzymatic and genetic test (ie, polymerase chain reaction) followed by Sanger sequence analysis of 4 variants of the gene (ie, c.2846A>T, and 1129-5923C>G; allele frequencies 0.58%, 0.03%, 0.29%, and 1.35%, respectively). Patients who have 1 of the 4 variants tested (n = 814) have lower enzyme activity than the overall patient group. The majority of patients with the variant (83%) consistently showed decreased enzyme activity. Only 24 (25.3%) of 95 patients (tested for 4 variants) with low enzyme activity carried a variant. Complete sequencing in a subgroup with low enzyme activity and without variant (n = 47) revealed 10 genetic variants, of which 4 have not been described previously. We did not observe a strong link between genotype and enzyme activity.
Conclusions: Previous studies have shown that DPD status should be determined before treatment with fluoropyrimidine agents to prevent unnecessary side effects with possible fatal consequences. Our study in combination with literature shows that there is a discrepancy between the DPD enzyme activity and the presence of clinically relevant single nucleotide polymorphisms. At this moment, a combination of a genetic and enzyme test is preferable for diagnostic testing. (. 2018; 79:XXX-XXX).
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http://dx.doi.org/10.1016/j.curtheres.2018.10.001 | DOI Listing |
J Dermatol Sci
January 2025
Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; Department of Frontier Science and Interdisciplinary Research, Faculty of Medicine, Kanazawa University, Ishikawa, Japan. Electronic address:
Background: Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.
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January 2025
School of Biological and Food Engineering, Guangxi Science & Technology Normal University, Laibin, Guangxi 546199, China. Electronic address:
Targeting DNA repair mechanisms, particularly PARP-1 inhibition, has emerged as a promising strategy for developing anticancer therapies. we designed and synthesized two 2-thiazolecarboxaldehyde thiosemicarbazone palladium(II) complexes (C1 and C2), and evaluated their anti-cancer activities. These Pd(II) complexes exhibited potent PARP-1 enzyme inhibition and demonstrated considerable antiproliferative activity against various cancer cell lines.
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January 2025
Department of Basic Medical Sciences, Faculty of Medicine, Istanbul Medipol University, Istanbul 34815, Türkiye.
The COVID-19 pandemic began in March 2020 and has affected many countries and infected over a million people. It has had a serious impact on people's physical and mental health, daily life and the global economy. Today, many drugs show limited efficacy in the treatment of COVID-19 and studies to develop effective drugs continue.
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January 2025
College of Life Science, Yangtze University, Jingzhou, China. Electronic address:
Tyrosinase is a rate-limiting enzyme for melanogenesis and abnormal melanin production can be controlled by utilizing tyrosinase inhibitory substances. To develop potent and safe inhibitors of tyrosinase, complex tannins a narrowly distributed plant polyphenols were prepared from the fruit peel of Euryale ferox (EPTs) and then structurally characterized, as well as investigated for their inhibitory effects and the involved mechanisms against tyrosinase activity and melanogenesis. The structures of EPTs were established to consist of 63.
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January 2025
College of Technology and Engineering, MPUAT, Udaipur, Rajasthan-313001, India. Electronic address:
Lipases, enzymes that perform the hydrolysis of triglycerides into fatty acids and glycerol, present a potential paradigm shift in the realms of food and detergent industries. Their enhanced efficiency, energy conservation and environmentally friendly attributes make them promising substitutes for chemical catalysts. Motivated by this prospect, this present study was targeted on the heterologous expression of a lipase gene, employing E.
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