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Nucleosomes, complexes of DNA and histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of cancer, but also in autoimmune diseases and acute situations such as stroke, trauma, and during sepsis. Here, the clinical relevance of circulating nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of cancer is reviewed. Several studies have shown that levels of nucleosomes are significantly higher in serum and plasma of cancer patients in comparison to healthy controls. However, because of elevations of nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for cancer diagnosis. Concerning tumor staging, nucleosome levels correlate with tumor stage and presence of metastases in gastrointestinal cancer, but not in other tumor types. Prognostic value of circulating nucleosomes is found in lung cancer in univariate analyses, but not in multivariate analyses. Circulating nucleosomes are most informative for the monitoring of cytotoxic therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo- and radiotherapy. In addition, therapy outcome is already indicated by the nucleosomal course during the first week of chemo- and radiotherapy in patients with lung, pancreatic, and colorectal cancer as well as in hematologic malignancies. Despite their non-tumor-specificity, kinetics of nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Facing an era of promising new antitumor therapies, predictors of therapy response are needed for the individual management of treatment. In sera collected prospectively from 311 patients with advanced non-small cell lung cancer receiving first-line chemotherapy, changes in nucleosomal DNA fragments, cytokeratin-19 fragments (CYFRA 21–1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) were investigated and correlated with therapy response. In univariate analysis, high levels, slower and incomplete decline in nucleosomal DNA, CYFRA 21–1, and CEA predicted poor outcome. DNA concentrations at day 8 of the first therapeutic cycle and CYFRA 21–1 before start of the second cycle were identified as best predictive variables. In multivariate analysis, they predicted progression with a specificity of 100% in 29% of the cases earlier than imaging techniques. Thus, nucleosomal DNA and CYFRA 21–1 specifically identify a subgroup of patients with insufficient therapy response at the early treatment phase and showed to be valuable for disease management. [ABSTRACT FROM AUTHOR]

Background: Nucleosomes are cell death products that are elevated in serum of patients with diseases that are associated with massive cell destruction. We investigated the kinetics of circulating nucleosomes after cerebral stroke and their correlation with the clinical status. Methods: In total, we analyzed nucleosomes by ELISA in sera of 63 patients with early stroke daily during the first week after onset. For correlation with the clinical pathology, patients were grouped into those with medium to slight functional impairment (Barthel Index BI ≥50) and those with severe functional impairment (BI <50). Results: Patients with BI ≥50 showed a continuous increase in nucleosomes until day 5 (median: 523 arbitrary units, AU) followed by a slow decline. In contrast, patients with BI <50 showed a steeper initial increase reaching a maximum already on day 3 (869 AU). Both, days after stroke (p < 0.001) and BI (p < 0.001), had a significant influence on nucleosome concentrations, respectively. Consistently, patients with BI <50 had a significantly larger area under the curve (AUC/day) of nucleosome values during the first week after stroke (800 AU) than patients with BI ≥50 (497 AU; p = 0.031). Concerning the infarction volume, nucleosomes showed significant correlations for the concentrations on day 3 (r = 0.43; p = 0.001) and for the area under the curve (r = 0.34; p = 0.016). Conclusion: Even if nucleosomes are nonspecific cell death markers, their release into serum after cerebral stroke correlates with the gross functional status as well as with the infarction volume and can be considered as biochemical correlative to the severity of stroke. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]