Holdenrieder S, Stieber P, Bodenmüller H, Busch M, Fertig G, Fürst H, Schalhorn A, Schmeller N, Untch M, Seidel D
Institute of Clinical Chemistry, Klinikum der Universität München-Grosshadern, Munich, Germany.
Int J Cancer. 2001 Mar 20;95(2):114-20. doi: 10.1002/1097-0215(20010320)95:2<114::aid-ijc1020>3.0.co;2-q.
High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.
大量的单核小体和寡核小体在恶性肿瘤患者的血液中循环。为了在血清中对其进行直接定量，我们对细胞死亡检测（增强型）酶联免疫吸附测定法进行了改良，使其适用于液体样本。我们检测了590人的血清样本，其中包括418例恶性肿瘤患者、109例良性疾病患者和63名健康人。我们还观察了20例接受化疗的患者和16例接受放疗的患者血清样本中核小体浓度的变化动力学。与健康人（平均 = 36任意单位[AU]，中位数 = 24 AU；p = 0.0001）和良性疾病患者（平均 = 264 AU，中位数 = 146 AU；p = 0.072）相比，恶性肿瘤患者血清中核小体浓度显著更高（平均 = 350 AU，中位数 = 190 AU）。关于随访研究，化疗首次应用后24 - 72小时以及放疗开始后6 - 24小时，血清中核小体浓度升高。随后的降低通常与肿瘤消退相关。在接受化疗的患者中，每个新治疗周期前测定的循环核小体基线值增加>50%与疾病进展相关；所有疾病缓解的患者基线值下降>50%。在接受放疗的患者中，核小体浓度在治疗初始峰值后早期降低（≤1天）至低水平（≤100 AU）与良好的临床结局相关；晚期降低（>1天）至高最低水平（>100 AU）与较差的临床结局相关。因此，血清中核小体浓度可能是监测抗肿瘤治疗期间生化反应的有用工具，尤其是用于早期评估治疗效果。
