Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.
Bottom Line: JNJ-28841072 suppressed in vitro phosphorylation of histone H3 with induction of cell polyploidy and death in a dose-dependent manner (IC50 = 0.8-1.2 μM).Our preclinical studies indicate that JNJ-28841072 is a promising novel therapeutic approach for the treatment of HCC.It might be worthy of evaluation in further studies.
Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.Show MeSH
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Mentions: The liver xenograft model in HuH-7 described above was subjected to histological analysis by immunostaining to investigate the pharmacobiological effects of JNJ-28841072 in the hepatic microenvironment. Twenty-four hours after treatment with JNJ-28841072, there was a substantial decrease in PhH3 compared with the control (Fig.4). One week after treatment with JNJ-28841072, the total blood vessel area were substantially decreased by treatment with JNJ-28841072 and distance between tumor vessels and adjacent ischemic area compared with the control (Fig.5). Similar results were observed in SK-Hep1 orthotopic xenografts by treatment with JNJ-28841072 (Figs4c,d and 5d,e). The hepatocytes from the host liver were histologically normal at all points following JNJ-28841072 administration.
Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.