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The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5-azacytidine in human bladder cancer therapy by Jose A. Karam; Jinhai Fan; Jennifer Stanfield; Edmond Richer; Elie A. Benaim; Eugene Frenkel; Peter Antich; Arthur I. Sagalowsky; Ralph P. Mason; Jer-Tsong Hsieh is a Medicine article available to read on EtoBox.
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## Abstract The long‐term disease‐free survival in patients with metastatic transitional cell carcinoma (TCC) is still considerably low. Novel chemotherapeutic agents are needed to decrease the morbidity and mortality of TCC. In this study, we have evaluated several epigenetic modifiers for their therapeutic application in bladder cancer. Both histone deacetylase inhibitors (FK228, TSA) and DNA hypomethylating agent (5‐Azacytidine) were tested using __in vitro__ assays such as cell viability, cell cycle analysis and western blot to determine their mechanisms of action. Drug combination experiments were also designed to study any additive or synergistic effects of these agents. In addition, two bladder cancer xenograft models (one subcutaneous and one orthotopic) were employed to assess the therapeutic efficacy of these agents __in vivo__. Three agents exhibited various growth inhibitory effects on 5 different TCC cell lines in a dose‐ and time‐dependent manner. In addition to G~2~/M cell cycle arrest, FK228 is more potent in inducting apoptosis than the two other single agents, and combination of both FK228 and 5‐Aza further enhances this effect. p21 induction is closely associated
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- Author
- Jose A. Karam; Jinhai Fan; Jennifer Stanfield; Edmond Richer; Elie A. Benaim; Eugene Frenkel; Peter Antich; Arthur I. Sagalowsky; Ralph P. Mason; Jer-Tsong Hsieh
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)
- Published
- 2007
- Language
- EN
- Field
- Medicine (Health Sciences)