The in vivo studies also supported the findings and showed better comprehensive residence time (23.61 ± 1.75 h), tumor distribution profile than UCN 01 alone.
The UCN immunoscore was high in all 9 normal gastric mucosa specimens, significantly lower in poorly differentiated gastric adenocarcinoma than in well and moderately differentiated tumors (P=0.018), and significantly lower in more advanced pathologic stages of gastric adenocarcinomas than in the early stages of these tumors.
Several clinical trials of UCN-01 alone or in combination with other agents for different tumour types are currently underway, and some of these trials have had positive results.
In two-drug combinations with GCV plus one of the four other drugs, increased tumor cell killing was found with GCV plus UCN-01 or with some GCV/butyrate combinations; the other two tested combinations were largely antagonistic.
UCN-01 (7-hydroxy-staurosporine), a selective inhibitor of protein kinase C (PKC), was shown to exhibit antitumor activity in murine and human tumor cell lines in vitro and in vivo.
All these events were suppressed by exposure to 10-100 nM UCN-01 or to calphostin C. Our findings suggest that the tumor promoter enhancement of EBV growth transformation is probably mediated by PKC.