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- W1430796619 abstract "Proc Amer Assoc Cancer Res, Volume 45, 20042449 FK228 is a novel antitumor agent that inhibits histone deacetylase. It has broad antitumor activity in preclinical studies and is currently under phase I/II evaluations. As histone deacetylase inhibitor is new category antitumor agent, effects of combination chemotherapy of histone deacetylase inhibitor with antitumor agents are poorly understood. To investigate its potential for inclusion in combination chemotherapy, we studied the optimal schedule of FK228 and various anticancer agents (cisplatin, taxol, adriamycin, etoposide and 5fluorouracil) in combination at various schedules in vitro using human prostate cancer DU-145 cells. Cells were simultaneously exposed to FK228 and antitumor agent for 24 h or sequentially exposed to FK228 for 24 h followed antitumor agent for 24 h or vice versa. Cell growth inhibition after 5 days was determined by MTT assay. The effects of drug combinations at the concentration of drug that produced 80% cell growth inhibition (the IC80 level) were analyzed by the isobologram method. The simultaneous exposure to FK228 and cisplatin, taxol, adriamycin, etoposide or 5fluorouracil produced additive to synergistic effects in DU-145 cells. The sequential exposure to anticancer agents followed by FK228 produced additive to synergistic effects in the cells. The sequential exposure to FK228 followed by taxol showed antagonistic effect in the cells. These findings suggest that a sequential administration the anticancer agents followed by FK228 may be the appropriate schedule for this combination. On the basis of the observed in vitro synergism, further in vivo and clinical studies are necessary to clarify the toxicity and proposed antitumor effects of this schedule." @default.
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- W1430796619 date "2004-04-01" @default.
- W1430796619 modified "2023-09-23" @default.
- W1430796619 title "The cytotoxic effects of FK228, histone deacetylase inhibitor, in combination with other anticancer agents." @default.
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