44 Metformin and its impact on gastric cancer patients survival after gastrectomy

2014 
and Q-PCR. The status of TP53 in ALL cells was determined by Sanger sequencing. Results: Nine ALL cell lines exhibited different susceptibilities to Aurora kinase inhibitors (AKIs). Cells sensitive to AKIs underwent apoptosis at an IC50 of approximately 10 to 30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 mM) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility was not correlated with the expression level or activation status of Aurora kinases. RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora-A inhibitors. CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to AKIs. Conclusions: Our study suggests that Aurora-A kinase inhibitors may have clinical utility in MLL-AF4-positive ALL. CDKN1A can be used as a biomarker to determine drug responsiveness in MLL-AF4-positive ALL.
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