P127	Long-term observation reveals time course dependent functional and morphological characteristics of tumorvascularization.
1C.Joscheck, 1Chr.Schaefer, 2K.Lamszus, 1L.Wolfram, 1T.Biermann, 3P.Algenstaedt, 4C.Heintz, 5W.Fiedler, 1W.Rüther, 1N.Hansen-Algenstaedt
1Department of Orthopaedic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, DE; 2Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, DE; 3Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, DE; 4Department of Vascular and Abdominal Surgery, AK Harburg, Hamburg, DE; 5Department of Internal Medicine II, University Hospital Hamburg-Eppendorf, Hamburg, DE.

Functional properties of tumor vasculature influence processes of metastasis and play a role in generating heterogeneous metabolic microenvironment contributing to genetic instability and inefficiency of tumor therapies. Because morphological and functional properties of tumor vasculature may vary from tumor onset until late stage disease, aim of the study was to identify dynamic alterations of tumor microcirculation in a chronic observation model. Methods: Invasively growing, non-disseminating, green fluorescent protein transfected human bone marrow derived endothelial cells, were implantated into cranial windows of severe combined immunodeficient mice. Intravital fluorescence microscopy was performed over a period of 85 days to measure permeability, leukocyte-endothelial-interactions and tissue perfusion rate as functional parameters. Vessel density, branching pattern and scanning electron microscopic analysis were monitored as morphological parameters. Results: Concordant with increasing count of transendothelial pores, the initial event following tumor cell implantation was a significant increase in permeability of pre-existing vessels. The variations of newly built vessels were characterized by sequentially occurring functional and morphological alterations with the development of characteristics typical for tumor vessels such as increased count of trifurcations and variation of vessel caliber by more than 100%. Parallel to increasing vessel volume per area, tissue perfusion rate increased until day 61. Tumor growth in cranial window (epiillumination and fluorescence microscopy) at day 0, 13, 35 and 85 Conclusions: From the step specific sequential functional and morphological alterations we conclude that efficiency of adjuvant therapies depend not only on their intrinsic efficiency but also on the timing when they are initiated.

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