ArticlePharmaceutical research2015
Significantly decreased and more variable expression of major CYPs and UGTs in liver microsomes prepared from HBV-positive human hepatocellular carcinoma and matched pericarcinomatous tissues determined using an isotope label-free UPLC-MS/MS method.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- Maternal-Fetal Physiologically Based Population Pharmacokinetics Model Development of Lopinavir/Ritonavir in HIV/HBV Co-infected Pregnant Women to Quantitatively Describe the Gestational PK Characteristics and Predict the Potential Disease-Drug-Drug Interaction (DDDI).Clinical pharmacokinetics · 2025Article
- Development of a PBPK Model for Lamotrigine which Incorporates Metabolism by UGT2B10: Impact of UGT2B10 Poor Metabolizer Phenotype and Pregnancy.The AAPS journal · 2025Article
- Quantitative Proteomics of Hepatic Drug-Metabolizing Enzymes and Transporters in Patients With Colorectal Cancer Metastasis.Clinical pharmacology and therapeutics · 2022Article
- CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling.Journal of translational medicine · 2022Article
- Hepatic CYP3A4 Enzyme Compensatively Maintains Endogenous Geranylgeranoic Acid Levels inMetabolites · 2022Article
- Proteomics of colorectal cancer liver metastasis: A quantitative focus on drug elimination and pharmacodynamics effects.British journal of clinical pharmacology · 2022Article
- Advanced oxidation protein products downregulate CYP1A2 and CYP3A4 expression and activity via the NF-κB-mediated signaling pathway in vitro and in vivo.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
- Identification and validation of ADME genes as prognosis and therapy markers for hepatocellular carcinoma patients.Bioscience reports · 2021Article
- Beyond the Michaelis-Menten: Accurate Prediction of In Vivo Hepatic Clearance for Drugs With Low KClinical and translational science · 2020Article
- Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters.Molecules (Basel, Switzerland) · 2020Review
- Article
- Label-free absolute protein quantification with data-independent acquisition.Journal of proteomics · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
- Critical Issues and Optimized Practices in Quantification of Protein Abundance Level to Determine Interindividual Variability in DMET Proteins by LC-MS/MS Proteomics.Clinical pharmacology and therapeutics · 2018Review
- LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine.Scientific reports · 2017Article
- Article
- Severely Impaired and Dysregulated Cytochrome P450 Expression and Activities in Hepatocellular Carcinoma: Implications for Personalized Treatment in Patients.Molecular cancer therapeutics · 2015Article
- Multiplexed Targeted Quantitative Proteomics Predicts Hepatic Glucuronidation Potential.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Quantitative profiling of human renal UDP-glucuronosyltransferases and glucuronidation activity: a comparison of normal and tumoral kidney tissues.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeTo determine the liver expression of cytochrome P450 (CYPs) and uridine 5'-diphosphate-glucuronosyltransferases (UGTs), the major phase I and II metabolism enzymes responsible for clearance and detoxification of drugs, xenobiotic and endogenous substances.
methodsA validated isotope label-free method was established for absolute and simultaneous quantification of 9 CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D, 2E1 and 3A4) and 5 UGTs (1A1, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes using LC-MS/MS.
resultsThe LC-MS/MS method displayed excellent dynamic range (at least 250-fold) and high sensitivity for each of the signature peptides with acceptable recovery, accuracy and precision. The protein expression profile of CYP and UGT isoforms were then determined in match microsomes samples prepared from patients with HBV-positive human hepatocellular carcinoma (HCC). In the tumor microsomes, the average absolute amounts of 8 major CYP isoforms (except CYP2C19) and 3 UGT isoforms (UGT1A1, UGT1A4 and UGT2B7) were decreased significantly (p < 0.05), whereas UGT1A6 and UGT1A9 levels were unchanged (p > 0.05). In addition, among isoforms with altered expression, 6 of 8 CYP isoforms and all three UGT isoforms were much more variable in tumor microsomes. Lastly, the importance of CYP3A4 was greatly diminished whereas the importance of UGT1A6 was enhanced in tumor microsomes.
conclusionThe use of an isotope label-free absolute quantification method for the simultaneous determination of 9 CYPs and 5 UGTs in human liver microsomes reveals that expression levels of CYPs and UGTs in human liver are severely impact by HCC, which could impact drug metabolism, disposition and pharmacotherapy.
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