Various cytostatic drugs have been used in combination with DSM, for example, mitomycin C, doxorubicin, epirubicin, or cisplatin, showing a significant better

tumor response [12, 13]. Objective clinical response rates up to 88% have been shown by some published clinical trials [21, 22]. More recently Vogl and coworkers published data from 462 patients with liver metastases from colon cancer, which were treated with DSM combined with a cytostatic drug showing an Inhibitors,research,lifescience,medical improved median overall survival (38 months) after primary diagnosis compared to reported data using intravenous applied chemotherapy [23]. Although several clinical and experimental data are published about the effect of DSM in Inhibitors,research,lifescience,medical cancer treatment, it is still not fully clarified what happens within the blood vessel during the degradation processes. The aim of the present study was to visualize and measure the accumulation of 5-FU combined with DSM into healthy liver as well as into liver tumor tissue of experimental directly induced liver cancer in rats using intravital microscopy and biochemical measurement, respectively. Furthermore, the all targets processes of degradation of DSM are visually monitored in order to get more insight into

the mechanism of the degradation to fully understand the resulting increased drug uptake into the liver tumor lesion. 2. Material and Methods To investigate the processes of DSM degradation, DSM based occlusion Inhibitors,research,lifescience,medical of Inhibitors,research,lifescience,medical blood vessels, and DSM based drug accumulation into healthy liver as well as into experimental liver tumors of rats, the technique of intravital microscopy was used. For optimal visualization, DSM and 5-FU were labelled with fluorescein dye (FITC). 2.1. Experimental Animals The experimental animals were WAG/Rij-rats (Wistar

Albino Glaxo), weighting between 250 and 300g, at our disposal. They were fed with standard rat food with free access to water. Animals were used in accordance with the national guidelines for the care and use of laboratory animals. 2.2. Experimental Liver Tumor Experimental Inhibitors,research,lifescience,medical rat liver tumors Cilengitide were prepared by using the tumor cell line CC531, which is a moderately differentiated adenocarcinoma originating from the colon of rats exposed to methylazoxymethanol. The ready for injection CC531-adenocarcinoma cells were kindly provided by the study group “drug targeting,” Max-Delbrück-Centre for molecular-diagnostic medicine, Berlin-Buch [24]. The tumor cells were implanted into the rat liver, which is an established model for human liver metastasis of colorectal carcinoma. 12 hours prior to tumor cell implantation rats were restrained from food. Anaesthesia was performed by intramuscular injection of Xylazine (12mg/kg) and Ketamine-HCL (80mg/kg). Additional anaesthesia was given intravenously, whenever necessary. Subsequently, the rats were dissected by a midline abdominal incision through the linea alba.