It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

No abstract

The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISA plus (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\\biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CV intraassay :3.0-4.1%) and between several runs (CV interassay :8.6-13.5%), and tested the analytical specificity of the ELISA.Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 °C, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples.As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n=220; mean=361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n=50; mean=30 AU; p=0.0001) and patients with inflammatory diseases (n=40; mean= 296 AU; p=0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (p=0.0004).

In the nucleus of eukaryotic cells, DNA is associated with several protein components and forms complexes known as nucleosomes. During cell death, particularly during apoptosis, endonucleases are activated that cleave the chromatin into multiple oligo-and mononucleosomes. Subsequently, these nucleosomes are packed into apoptotic bodies and are engulfed by macrophages or neighboring cells. In cases of high rates of cellular turnover and cell death, they also are released into the circulation and can be detected in serum or plasma. As enhanced cell death occurs under various pathologic conditions, elevated amounts of circulating nucleosomes are not specific for any benign or malignant disorder. However, the course of change in the nucleosomal levels in circulation of patients with malignant tumors during chemotherapy or radiotherapy is associated with the clinical outcome and can be useful for the therapeutic monitoring and the prediction of the therapeutic efficacy.

Background. It is known that cytokeratin 19 is particularly abundant in carcinoma of the lung. Methods. A sandwich enzyme‐linked immunosorbent assay called CYFRA 21‐1 was, therefore, developed to detect soluble cytokeratin 19 fragments in serum using two specific monoclonal antibodies (Ks 19.1 and BM 19.21). The authors investigated the clinical significance of this new marker compared with the established markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron‐specific enolase (NSE), carbohydrate antigen (CA) 19–9, CA 125, CA 15–3, CA 72–4, alpha‐fetoprotein, and prostate‐specific antigen in a pilot study on 1741 serum samples from patients with various benign and malignant diseases. Results. Postulating a specificity of 95% versus benign diseases of the lung, the diagnostic sensitivity of CYFRA 21‐1 in lung cancer (independent of histologic type) at primary diagnosis was superior (47%) to CEA (27%), SCC (15%), and NSE (16%). Especially in squamous cell carcinomas of the lung, the true‐positive test results were much higher for CYFRA 21‐1 (60%) than for CEA (18%) or SCC (31%). Conclusions. In small cell lung carcinomas, NSE was confirmed as the marker of first choice. For all of the other solid tumors investigated, CYFRA 21‐1 showed no better profile of specificity and sensitivity than the established markers.