title: Annexin V-targeted enzyme prodrug therapy using cytosine deaminase in combination with 5-fluorocytosine.
abstract: A fusion protein, consisting of cytosine deaminase (CD) linked to human annexin V, was created for use in an enzyme prodrug therapy targeted to the tumor vasculature and associated cancer cells in the primary tumor and distant metastases. The major finding of this study is that the CD-annexin V fusion protein in combination with the prodrug 5-fluorocytosine has significant cytotoxic activity against endothelial cells and two breast cancer cells lines in vitro that expose phosphatidylserine on their surface. The cytotoxicity experiments verified this novel enzyme prodrug system has the ability to produce therapeutic levels of 5-fluorouracil and thus appears promising.
authors.affiliation: Bioengineering Center and the School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, OK, USA.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Van Rite
authors.affiliation: Bioengineering Center and the School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, OK, USA. Electronic address: rharrison@ou.edu.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Harrison
mesh_terms: D017304:Annexin A5 / Q000235:genetics*; D000963:Antimetabolites / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D005437:Flucytosine / Q000494:pharmacology*; D005472:Fluorouracil / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000963:Antimetabolites; D010718:Phosphatidylserines; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D043525:Cytosine Deaminase; D005472:Fluorouracil