Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition

Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy

Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance

Das Preisverhalten des konzentrierten und des nicht konzentrierten Industriebereichs 1966-1976

The authors examine the hypothesis of price-rigidity in German industry. In this context an important statement, made 1978 by the "Monopolkommission" is discussed, which said, that there do not exist any significant differences between concentrated and non-concentrated industries concerning their behaviour during the cycle. The validity of Spearman's test on rank-correlation, which was used in the empirical investigation of the "Monopolkommission", is debated. Using Wilcoxon's test with rank-sums the authors come to the conclusion, that in certain phases of the cycle there do show up different patterns of behaviour. Some acceptable theoretical explanations of the observed phenomena are offered

Full and partial minimax estimation in regression analysis with additional linear constraints

AbstractThe linear regression model is considered where the parameter vector may be simultaneously constrained by an ellipsoid and inhomogeneous linear restrictions. Using the minimax approach, estimators are developed which combine sample information and prior constraints. Specific attention is paid to the case when the restrictions are valid only for a subvector

A note on least squares estimation with a particular linear function of the dependent variable

SIGLEBibliothek Weltwirtschaft Kiel YY11,511 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Preisstarheit, Inflation und -Gleichgewichte in multiplen Marktmodellen

SIGLEBibliothek Weltwirtschaft Kiel YY 11,511 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman