title: Augmented therapeutic efficacy of irinotecan is associated with enhanced drug accumulation.
abstract: The goal of this study is to determine whether treatment with methylselenocysteine (MSC) results in differential uptake of irinotecan and its active metabolite (SN-38) between tumors of head and neck squamous cell carcinomas and normal tissue. The in vivo synergy between MSC and irinotecan is influenced by treatment schedule and associated with enhancement of tumor vessel maturation, intra-tumor concentration of SN-38 and apoptotic death of tumor cells. Normal tissue drug concentrations were not impacted by selenium treatment. The finding is of clinical relevance for enabling the delivery of higher doses of irinotecan to reverse tumor resistance, recurrence and ultimately enhancing cure rates.
authors.affiliation: Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Azrak@roswellpark.org
authors.forename: Rami G
authors.initials: RG
authors.lastname: Azrak
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
authors.forename: Farukh A
authors.initials: FA
authors.lastname: Durrani
authors.forename: Karoly
authors.initials: K
authors.lastname: Toth
authors.forename: Arup
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Youcef M
authors.initials: YM
authors.lastname: Rustum
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D017279:Selenocysteine / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D017279:Selenocysteine; D000077146:Irinotecan; D003545:Cysteine; C002979:selenomethylselenocysteine; D002166:Camptothecin