Advanced animal model systems for solid tumor therapy research (Dr. T.L.M. ten Hagen) Research is focussed on the treatment of solid tumors and in particular melanoma and sarcoma.this is done by development and improvement of real-time studies on tumor vascular events by intravital fluorescence microscopy. Treatment modalities are developed which improve local drug delivery by physical isolation of the diseased site with the aid of vaso-active agents, the activity of concomitant chemotherapy is improved. The mechanism of TNF on endothelial cell function, tumor vascular permeability and vascular function is studied. Also the influence of other cytokines, in particular IFN and EMAP-II, is under study. The mechanism of angiogenesis and metastasis in malignant melanoma is studied. The effect and mechanism of agents acting on integrin-matrix interaction is studied in relation with endothelial cell function, tumor vascular integrity and solid tumor therapy. In vivo reaction mechanisms of steroid regulated gene transcription and DNA repair (Dr. A.B. Houtsmuller). Current research focusses on in vivo reaction mechanisms of gene transcription and DNA repair. We use genetic fluorescent labeling of transcription factors and DNA-repair factors and study their functioning in living cells with confocal time-lapse imaging and quantitative fluorescence assays such as fluorescence recovery after photobleaching (FRAP), fluorescence resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS). In addition, for optimal interpretation of the complex and massive amount of experimental results we develop computer modeling to simulate both FRAP and FRET assays as well as protein behavior.