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Title: Predicting in Vivo Anti-Hepatofibrotic Drug Efficacy Based on In Vitro High-Content Analysis
Keywords: liver fibrosis; hepatic stellate cells; high-content analysis; in vitro-in vivo correlation; anti-fibrotic drugs; drug efficacy
Issue Date: 13-May-2011
Citation: ZHENG BAI XUE (2011-05-13). Predicting in Vivo Anti-Hepatofibrotic Drug Efficacy Based on In Vitro High-Content Analysis. ScholarBank@NUS Repository.
Abstract: Many potential anti-fibrotic drugs with high in vitro efficacies fail to produce significant effects in vivo. The aim of this project is to design an in vitro numerical predictor that correlates better with in vivo outcomes. High-content analysis (HCA) was performed with 49 drugs on hepatic stellate cells (HSCs) stained with 10 markers of fibrosis. The output, termed Epredict, could linearly correlate with the in vivo data from fibrotic rat models. Sulfasalazine, pioglitazone and glycyrrhizin were found to have the highest anti-fibrotic efficacy represented by Epredict; while most of the anti-oxidants showed low efficacy. Similar results were observed from published human clinical studies. Furthermore, we demonstrated three applications of Epredict to study the characteristics and similarities of drugs with potent anti-fibrotic effect. In conclusion, the Epredict statistic provides a better correlation between in vitro and in vivo drug response than any of the traditional in vitro markers considered.
Appears in Collections:Ph.D Theses (Open)

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