ArticleEuropean journal of histochemistry : EJH2016
Immunohistochemical markers of CYP3A4 and CYP3A7: a new tool towards personalized pharmacotherapy of hepatocellular carcinoma.
Article in European journal of histochemistry : EJH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Curcumin for gastric cancer: Mechanism predictionWorld journal of gastrointestinal oncology · 2024Article
- Exploring the Molecular Mechanisms of Huaier on Modulating Metabolic Reprogramming of Hepatocellular Carcinoma: A Study based on Network Pharmacology, Molecular Docking and Bioinformatics.Current pharmaceutical design · 2024Article
- Stem/progenitor cells in fetuses and newborns: overview of immunohistochemical markers.Cell regeneration (London, England) · 2021Review
- Identification of Multiple Hub Genes and Pathways in Hepatocellular Carcinoma: A Bioinformatics Analysis.BioMed research international · 2021Article
- Gene Expression Characteristics of Liver Tissue Reveal the Underlying Pathogenesis of Hepatocellular Carcinoma.BioMed research international · 2021Article
- Prognostic Score-based Clinical Factors and Metabolism-related Biomarkers for Predicting the Progression of Hepatocellular Carcinoma.Evolutionary bioinformatics online · 2020Article
- Predict New Therapeutic Drugs for Hepatocellular Carcinoma Based on Gene Mutation and Expression.Frontiers in bioengineering and biotechnology · 2020Article
- Histochemistry as a versatile research toolkit in biological research, not only an applied discipline in pathology.European journal of histochemistry : EJH · 2018Article
- Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is useful in diagnosis of HBV-related hepatocellular carcinoma with higher specificity and sensitivity.European journal of histochemistry : EJH · 2018Article
- Histochemistry today: Detection and location of single molecules.European journal of histochemistry : EJH · 2017Article
- Is there still room for novelty, in histochemical papers?European journal of histochemistry : EJH · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) represents a major global health problem, since more than 90% of primary liver cancers worldwide are HCC. Most cases of HCC are secondary to viral hepatitis infection (hepatitis B or C), alcoholism and cirrhosis. Sorafenib, an oral tyrosine kinase inhibitor that suppresses tumor proliferation and angiogenesis, emerged as the first effective systemic treatment for HCC after 30 years of research, and is currently the standard-of-care for patients with advanced HCC. Sorafenib is metabolized by cytochrome P450 (CYP450), particularly from the 3A4 isoform, producing two main metabolites: the N-oxide and the N-hydroxymethyl metabolite. We studied 11 HCC sample showing the presence of CYP3A4 and CYP3A7 in most of the samples analyzed. Specifically, the immunoreactivity of CYP3A4 was more strong and widespread than that of CYP3A7. The CYP3A4 immunoreactivity was observed in surrounding hepatocytes in 8 out of 11 cases; while the CYP3A7 immunostaining was found in normal liver cells, in 7 out of 11 cases. These results suggest the existence of a marked inter-individual variability regarding the presence of the isoforms of CYP3A. In addition, since sorafenib is metabolized by CYP3A4, but not by CYP3A7, an overexpression of CYP3A4 may lead to an increase in the degradation of the drug and then to clinical ineffectiveness. These results might implicate the necessity of an individualized approach in the treatment of HCC as positivity to CYP3A4 in HCC liver samples might predict a scarce response to sorafenib.
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