Nucleosomes in serum of patients with benign and malignant diseases

High quantities of mono- and oligonucleosomes circulate in the blood of pat ients with malignant tumors. For their direct quantification in serum, we m odified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patient s with malignant tumors, 109 patients with benign diseases and 63 healthy p ersons. We also observed the kinetics of the concentration of nucleosomes i n serum samples from 20 patients undergoing chemotherapy and from 16 patien ts undergoing radiotherapy. Sera of patients with malignant tumors containe d considerably higher concentrations of nucleosomes (mean = 350 arbitrary u nits [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 investigati ons, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiother apy. A subsequent decrease was often correlated with regression of the tumo r. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new ther apeutic cycle, was correlated with progression of disease; all patients wit h disease regression showed a decrease >50% of the baseline values. In pati ents undergoing radiotherapy, an early decrease of the nucleosomal concentr ation (11 day after the initial peak during therapy) to low minimum levels (less than or equal to 100 AU) correlated with good clinical outcome; a lat e decrease (> 1 day) to higher minimum levels (> 100 AU) was associated wit h a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during anti tumor therapy, especially for the early estimation of therapeutic efficacy, (C) 2001 Wiley-Liss, Inc.