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Pharmacokinetics And Toxicity Of The Novel Oral Demethylating Agent Zebularine In Laboratory And Tumor Bearing Dogs, Christopher Michael Fulkerson

Open Access Theses

The aim of this thesis is to investigate the pharmacokinetics and toxicity of the novel oral demethylating agent zebularine (zeb) in laboratory dogs and tumor bearing dogs. This thesis focuses on the application of this therapeutic strategy in dogs with naturally occurring invasive transitional cell carcinoma (InvTCC), which serve as a relevant model of the human disease.

DNA hypermethylation in the promoter region is a common epigenetic change in cancer that silences tumor suppressor genes. Zeb is an oral cytidine analog that acts as a demethylating agent. Zeb has been investigated extensively in vitro as well as in mice, rodents …