title: Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts.
abstract: BACKGROUND
  Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy.
  
  
  METHODS
  To determine, whether caspase activation can predict the chemosensitivity, we investigated enzyme activation of caspase-3, a key executioner caspase and correlated these data with chemosensitivity profiles of acute myeloid leukemia (AML) blasts.
  
  
  RESULTS
  There was, however, no correlation between the ex-vivo chemosensitivity assessed by measuring the overall rates of cell death by use of the DiSC-assay and caspase-3 activation.
  
  
  CONCLUSIONS
  Thus, despite a significant reduction of duration of the assay from four to one day, induction of apoptosis evaluated by caspase-3 activity does not seem to be a valid surrogate marker for chemosensitivity.
authors.affiliation: Clinic I for Internal Medicine, The University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany. peter.staib@uni-koeln.de
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Jan
authors.initials: J
authors.lastname: Tiehen
authors.forename: Timo
authors.initials: T
authors.lastname: Strunk
authors.forename: Timo
authors.initials: T
authors.lastname: Schinköthe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013050:Spectrometry, Fluorescence; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D003561:Cytarabine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D003630:Daunorubicin