Blood Cells Of Healthy Controls Research Articles

High-throughput miRNA profiling of human melanoma blood samples

BackgroundMicroRNA (miRNA) signatures are not only found in cancer tissue but also in blood of cancer patients. Specifically, miRNA detection in blood offers the prospect of a non-invasive analysis tool.MethodsUsing a microarray based approach we screened almost 900 human miRNAs to detect miRNAs that are deregulated in their expression in blood cells of melanoma patients. We analyzed 55 blood samples, including 20 samples of healthy individuals, 24 samples of melanoma patients as test set, and 11 samples of melanoma patients as independent validation set.ResultsA hypothesis test based approch detected 51 differentially regulated miRNAs, including 21 miRNAs that were downregulated in blood cells of melanoma patients and 30 miRNAs that were upregulated in blood cells of melanoma patients as compared to blood cells of healthy controls. The tets set and the independent validation set of the melanoma samples showed a high correlation of fold changes (0.81). Applying hierarchical clustering and principal component analysis we found that blood samples of melanoma patients and healthy individuals can be well differentiated from each other based on miRNA expression analysis. Using a subset of 16 significant deregulated miRNAs, we were able to reach a classification accuracy of 97.4%, a specificity of 95% and a sensitivity of 98.9% by supervised analysis. MiRNA microarray data were validated by qRT-PCR.ConclusionsOur study provides strong evidence for miRNA expression signatures of blood cells as useful biomarkers for melanoma.

Sensitivity to Glucocorticoids Is Decreased in Relapsing Remitting Multiple Sclerosis

Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.