Figure 1.
Figure 1. DCK and UCK enzymes predict drug sensitivity. In cell lines representative of the histologic and genetic diversity of cancer (NCI60), the rate-limiting enzymes that determine the intracellular half-lives of decitabine and 5-azacytidine, DCK and UCK respectively, predicted drug sensitivity. Drug sensitivity is represented as GI50: the drug concentration causing 50% growth reduction. The higher the GI50, the less sensitive to drug, quantified by measurement of total protein at day 6 (raw data downloaded from the National Cancer Institute [http://dtp.nci.nih.gov] and GSE5846, gene expression by microarray). (A) Decitabine GI50 is inversely correlated with DCK expression and growth fraction (higher DCK implies longer intracellular half-life and a higher doubling time implies a smaller S-phase fraction). Decitabine GI50 did not correlate with UCK2 expression (data not shown). (B) 5-azacytidine GI50 inversely correlates with UCK2 expression and growth fraction. 5-Azacytidine GI50 did not correlate with DCK expression (data not shown). UCK1 expression was not available in this database.

DCK and UCK enzymes predict drug sensitivity. In cell lines representative of the histologic and genetic diversity of cancer (NCI60), the rate-limiting enzymes that determine the intracellular half-lives of decitabine and 5-azacytidine, DCK and UCK respectively, predicted drug sensitivity. Drug sensitivity is represented as GI50: the drug concentration causing 50% growth reduction. The higher the GI50, the less sensitive to drug, quantified by measurement of total protein at day 6 (raw data downloaded from the National Cancer Institute [http://dtp.nci.nih.gov] and GSE5846, gene expression by microarray). (A) Decitabine GI50 is inversely correlated with DCK expression and growth fraction (higher DCK implies longer intracellular half-life and a higher doubling time implies a smaller S-phase fraction). Decitabine GI50 did not correlate with UCK2 expression (data not shown). (B) 5-azacytidine GI50 inversely correlates with UCK2 expression and growth fraction. 5-Azacytidine GI50 did not correlate with DCK expression (data not shown). UCK1 expression was not available in this database.

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