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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]

We report the first experiences with HELP apheresis as an emergency treatment for acute cardiovascular syndromes; two patients who were not eligible for lysis therapy and catheter intervention were treated with HELP apheresis instead. Both patients had a most severe, generalized atherosclerosis and reached the hospital too late for conventional measures. In both cases, the use of the apheresis dramatically improved the clinical situation to such an extent that the possibilities of this apheresis system urge further investigation. [ABSTRACT FROM AUTHOR]

Approximately 30% of myeloma patients express cyclin D1 RNA and protein. The low incidence of translocation t(11; 14) detected by conventional cytogenetics suggests that the up-regulation of cyclin D1 protein might result from other mechanisms as well as from gene amplification. Therefore, the frequency and the clinical and prognostic implications of cyclin D1 amplification were examined. We highly purified myeloma cells from bone marrow by magnetic cell sorting and analysed 50 myelomas by fluorescence in situ hybridization (FISH) using probes specific for cyclin D1 and 20 samples by immunoblotting to detect cyclin D1 expression. The amplification of cyclin D1 gene was found in 19 of 50 analysed patients and was associated with expression of cyclin D1 protein. The amplification correlated significantly with the bone marrow infiltration, plasma cell morphology and labelling index as well as serum β2-microglobulin, C-reactive protein (CRP) and creatinine levels. In univariate analysis, the amplification of the cyclin D1 gene was a significantly unfavourable parameter with regard to overall survival (P = 0·0064) and progression-free survival (P = 0·0005). In multivariate analysis, cyclin D1 amplification and serum β2-microglobulin were independent and well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myeloma. [ABSTRACT FROM AUTHOR]

There is increasing evidence that atherogenic risk factors largely contribute to the pathogenesis of graft vessel disease (GVD) after heart transplantation. Initial endothelial damage of the transplant heart derives from reperfusion ischemia during operation, repeated infections, and rejection episodes. Immunosuppressive medication considerably increases low density lipoprotein (LDL) cholesterol, lipoprotein(a), and fibrinogen blood levels, which in turn further damage the endothelium of the graft coronaries. Probably, this interplay of immunological and atherogenic factors accounts for the rapid development of GVD and its poor prognosis. The rapidity of the disease process makes it necessary to eliminate important risk factors as early and as efficiently as possible. Therefore, we studied whether heart transplant patients could benefit from a combined treatment of statins and apheresis heparin extracorporeal LDL/fibrinogen precipitation (HELP), which has already been shown to be beneficial for the treatment of advanced coronary artery disease. Such a combined treatment allows simultaneous and drastic reduction of LDL, lipoprotein(a), and fibrinogen blood levels and significantly prevented GVD. Moreover, it did not affect the prevention of rejections and infections, respectively. [ABSTRACT FROM AUTHOR]