title: Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside.
abstract: BACKGROUND
  The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.
  
  
  METHODS
  After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.
  
  
  RESULTS
  Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.
  
  
  CONCLUSIONS
  Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.
authors: Pediatric Department, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, U.S.A. Pediatric Department, Taibah University, Madina, Kingdom of Saudi Arabia abeeraaa6@gmx.de.
authors: Abeer Abd
authors: AA
authors: Elmoneim
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, U.S.A.
authors: Elisabeth
authors: E
authors: Heuston
authors: Phoenix Children's Research Institute, Phoenix Children's Hospital, Phoenix, AZ, U.S.A.
authors: Daniel H
authors: DH
authors: Wai
authors: Department of Pathology, Children Hospital, Los Angeles, CA, U.S.A.
authors: Timothy
authors: T
authors: Triche
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, U.S.A.
authors: Robert J
authors: RJ
authors: Arceci
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D000077209:Decitabine; D001374:Azacitidine
keywords: Drug interaction; myeloid leukemia; pediatric cancer