Cancer Therapy: Preclinical Killing of Chronic Lymphocytic Leukemia by the Combination of Fludarabine and Oxaliplatin Is Dependent on the Activity of XPF Endonuclease

نویسندگان

  • Alma Zecevic
  • Deepa Sampath
  • Brett Ewald
  • Rong Chen
  • William Wierda
  • William Plunkett
چکیده

Purpose: Chronic lymphocytic leukemia (CLL) resistant to fludarabine-containing treatments responds to oxaliplatin-based therapy that contains fludarabine. We postulated that a mechanism for this activity is the incorporation of fludarabine into DNA during nucleotide excision repair (NER) stimulated by oxaliplatin adducts. Experimental Design: We analyzed CLL cell viability, DNA damage, and signaling pathways in response to treatment by fludarabine, oxaliplatin, or the combination. The dependency of the combination on oxaliplatin-induced DNA repair was investigated using siRNA in CLL cells or cell line models of NER

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Killing of chronic lymphocytic leukemia by the combination of fludarabine and oxaliplatin is dependent on the activity of XPF endonuclease.

PURPOSE Chronic lymphocytic leukemia (CLL) resistant to fludarabine-containing treatments responds to oxaliplatin-based therapy that contains fludarabine. We postulated that a mechanism for this activity is the incorporation of fludarabine into DNA during nucleotide excision repair (NER) stimulated by oxaliplatin adducts. EXPERIMENTAL DESIGN We analyzed CLL cell viability, DNA damage, and sig...

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تاریخ انتشار 2011