Staib Peter, Tiehen Jan, Strunk Timo, Schinköthe Timo
Clinic I for Internal Medicine, The University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
BMC Cancer. 2005 Jun 11;5:60. doi: 10.1186/1471-2407-5-60.
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.
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.
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.
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.
测量细胞死亡诱导的体外化学敏感性测试可以预测治疗结果，因此是癌症治疗临床决策的有力工具。然而，此类测试工作强度大，就DiSC检测而言，至少需要四天时间。诱导凋亡是抗癌药物的作用方式，因此，抗癌治疗靶向的细胞中应会诱导半胱天冬酶激活。
为了确定半胱天冬酶激活是否能预测化学敏感性，我们研究了关键执行半胱天冬酶-3的酶激活情况，并将这些数据与急性髓系白血病（AML）原始细胞的化学敏感性谱进行关联。
然而，通过DiSC检测测量细胞死亡总速率评估的体外化学敏感性与半胱天冬酶-3激活之间没有相关性。
因此，尽管检测时间从四天大幅缩短至一天，但通过半胱天冬酶-3活性评估的凋亡诱导似乎并不是化学敏感性的有效替代标志物。
