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2007 Program and Abstracts | 2007 Posters
Intravital Microscopic Characterization of Suramin Effects in An Orthotopic Immunocompetent Rat Model of Pancreatic Cancer
Birgit Hotz, Elisabeth Schellhaas, Heinz J. Buhr, Hubert G. Hotz*
Surgery I, Charite Medical School, Berlin, Germany

Suramin, a naphthyl urea derivative, reduces tumor growth and neoangiogenesis in a T-cell deficient nude mouse model of pancreatic cancer. The present study investigated the effects of Suramin on tumor growth and spread in a fully immunocompetent, orthotopic rat model of pancreatic cancer, and analyzed the tumor vasculature by intravital microscopy.
Methods: In vitro: Rat pancreatic cancer cells of ductal origin (DSL-6A/C1) were incubated with Suramin (10 - 800 µg/ml). Proliferation was assessed by cell count after 72 hours. In vivo: 10 million DSL-6A/C1 cells were injected sc. into Lewis rats. 1 cmm fragments of the resulting sc. tumors were implanted into the pancreas of 72 other rats. Animals were randomized into 2 groups and received either Suramin (60 mg/kg, weekly ip.) or the vehicle (controls). Treatment started 3 days after tumor induction. The pancreatic tail was exteriorized for intravital microscopy 1, 4, and 8 weeks after tumor induction (12 rats per group and time point). Diameter, density, and permeability of tumor vessels were analyzed. Primary tumor volume (TU-Vol), tumor spread (dissemination score: D-Score) were determined at autopsy. Microvessel density (MVD) was analyzed in CD31-stained tumor sections.
Results: In vitro: Cancer cell proliferation was inhibited by Suramin dose dependently by up to 95 %. In vivo: see table. All controls developed extensive tumor growth, local infiltration, and distant metastasis. In contrast, there was no tumor detectable in half of the Suramin-treated animals after 8 weeks; the other animals harbored small tumors. Dissemination in treated animals was almost completely depressed after 8 weeks. Control animals displayed irregular tumor blood vessels. Suramin therapy resulted in a complete regression of tumor macrovessels and a significant reduction of microvessel density.
Conclusion: Suramin significantly reduces primary tumor growth and dissemination in a clinically relevant rat model of ductal pancreatic cancer. Beside a direct effect on pancreatic cancer cell growth, Suramin seems to play an important role for the inhibition of tumor angiogenesis.
In vivo results

Group Vessel- diameter (µm) Vessel- density (1/cm) Vessel- permeability (#) TU-Vol. (cmm) D-Score (points) MVD (/0.74 smm)
Control (1 week)30.9 ± 4.6 72.4 ± 7.9105.6 ± 1.450 ± 120.3 ± 0.1 72.3 ± 5.0
Suramin (1 week) 20.1 ± 3.282.4 ± 5.8113.8 ± 3.2* 49 ± 13 0 76.8 ± 5.0
Control (4 weeks)28.4 ± 4.080.3 ± 5.1 112.8 ± 2.41286 ± 316 6.8 ± 1.6 79.7 ± 6.3
Suramin (4 weeks) 29.8 ± 5.183.6 ± 7.0 122.6 ± 2.8* 448 ± 180*5.8 ± 1.465.1 ± 6.2
Control (8 weeks) 52.2 ± 8.188.7 ± 4.7 112.9 ± 4.1 9118 ± 3011 10.3 ± 2.889.4 ± 5.4
Suramin (8 weeks)- -- 56 ± 38*0.4 ± 0.2* 30.2 ± 13.4*

* = p < 0.05 vs. respective control # = gray scale: 100 = normal tissue


2007 Program and Abstracts | 2007 Posters
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