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The cisplatin analogue 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) (DAP) is a DNA-damaging agent that will be entering clinical trials for its potent cytotoxic effects against cisplatin-resistant tumour cells. This cytotoxicity may reside in its ability to selectively activate G1-phase checkpoint response by inhibiting CDKs via the(More)
Osmotic response element binding protein (OREBP) is a Rel-like transcription factor critical for cellular osmoresponses. Previous studies suggest that hypertonicity-induced accumulation of OREBP protein might be mediated by transcription activation as well as posttranscriptional mRNA stabilization or increased translation. However, the underlying mechanisms(More)
1R,2R-Diaminocyclohexane(trans-diacetato)(dichloro)-platinum(IV) (DACH-acetato-Pt) is a novel platinum-based agent that is highly effective against cisplatin-resistant ovarian tumor cells. To probe its cellular mechanism, the effects of DACH-acetato-Pt (0-6.4 microM) on cell cycle checkpoints were examined using the ovarian cancer A2780 cell line as the(More)
Treatment of cells with agents that cause DNA damage often results in a delay in G2. There is convincing evidence showing that inhibition of p34cdc2 kinase activation is involved in the DNA damage-induced G2 delay. In this study, we have demonstrated the existence of an additional pathway, independent of the p34cdc2 kinase activation pathway, that leads to(More)
BACKGROUND In cycling tumour cells, the binary cyclin-dependent kinase Cdk4/cyclin D or Cdk2/cyclin E complex is inhibited by p21 following DNA damage to induce G1 cell-cycle arrest. However, it is not known whether other proteins are also recruited within Cdk complexes, or their role, and this was investigated. METHODS Ovarian A2780 tumour cells were(More)
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