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• W2345512270 abstract "Introduction: Tumour growth is dependent upon the balance of positive and negative regulators of angiogenesis. Antiangiogenic compounds such as antiangiogenic Antithrombin III (aaAT III) inhibit endothelial cell biology in vitro and angiogenesis in vivo. Until now it is unknown whether coagulation active Antithrombin (AT III) is effective as an antiangiogenic inhibitor. The aim of the study was to determine the effect of coagulation active AT III (Kybernin © ) on the growth of human pancreatic cancer in a mouse model (SCID). Methods: Human pancreatic cancer cell lines (BxPC3 and AsPC-1) were injected subcutaneously (s. c.) into the dorsa of male, immunodeficient (SCID) mice. When tumour volume was 100 mm 3 , mice were randomized into each five groups (n = 8/group) receiving Kybernin © (s. c.) (10, 50, 100, 200 mg/kg /day with n = 8 /group), latent AT III (antiangiogenic AT III) (100 mg/kg/day with n = 4/group) injections or Buffer (n = 5/group) as control for 19 days. Tumours were measured every 3–5 days and the tumour inhibition rate was determined for the last time point. Inhibitory effects of Kybernin © versus native (purified) AT III (0.1–20 mg/ml) on proliferation and migration was measured using micro- and macrovascular endothelial cell assays (BCE and HUVEC). Statistical analysis was performed. Results: Tumour inhibition rate (%) for BxPC-3 (slow growing tumour) was 69 % for 10 mg/kg/day, 90 % for 50 mg/kg/day 81 % for 100 mg/kg/day Kybernin © and 80 % for latent AT III (100 mg/kg/day). The inhibition of tumour growth was statistically significant in all treatment groups compared to placebo. For the fast growing tumour (AsPC-1) the inhibition rate was 44 % for 50 mg/kg/day, 46 % for 100 mg/kg/day, 56 % for 200 mg/kg/day Kybernin © and 65 % for latent AT III (100 mg/kg/day). The most effective dose with 90 % inhibition in the BxPC-3 model was 50 mg/kg/day. The same dosage in the AsPC-1 model leads to only 44 % inhibition. All mice gained weight throughout the study. A significant and dose dependent inhibition was observed in vitro for Kybernin © compared to native (purified) AT III in the migration and proliferation assay. Discussion: Coagulation active AT III (Kybernin © ) revealed significant inhibitory effects in vivo and in vitro. Depending on the angiogenic phenotype and the ability of different tumours to cleave native AT III by secreted enzymes to antiangiogenic AT III an effective tumour therapy with AT III (Kybernin © ) in combination with chemo- and/or radiation therapy or with other antiangiogenic" @default.
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• W2345512270 date "2006-01-01" @default.
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• W2345512270 title "Effektive Tumortherapie in SCID-Mäusen durch koagulations- aktives Antithrombin III Effective tumour therapy in SCID mice with coagulation active Antithrombin III" @default.
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