| Autor: |
C. Dietz, J. S. Becker, S. Hennig, I. Celik, Detlef K. Bartsch, V. Welter |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
Deutsche Gesellschaft für Chirurgie ISBN: 9783642006241 |
| DOI: |
10.1007/978-3-642-00625-8_21 |
| Popis: |
The dihydroorotate dehydrogenase (DHODH) is the fourth, enzyme in pyrimidine biosynthesis and is located in the inner mitochondrial membrane. Leflunomid is in clinical use for the treatment of rheumatoid arthritis. By entero-hepatic metabolisation the pro-drug leflunomid is transformed into the active metabolite A771726. A771726 inhibits specifically the DHODH enzyme and leads to significant reduction of UMP and hereby, because of the reduction of T-cell proliferation in rheumatoid arthritis, to decreased inflammatory reaction. Aim of the study was the investigation of the inhibitory effect of leflunomid and the active metabolite A771726 in vitro with the human pancreatic carcinoma cell lines BxPC-3 and AsPC-1 in proliferating assays. Proliferation inhibition was also analysed with HUVECs. Both inhibitors were also analysed according to the tumour growth inhibition in vivo in the SCID mouse model with BxPC-3 pancreatic carcinoma cells. Methods: Male immunodeficient mice (SCID), 6–8 weeks old were used. BxPC-3 pancreatic cancer cells (5×106) in 0.2 ml RPMI 1640 medium were implanted subcutaneously (s.c.) in the dorsa of the mice (n=5/group). Tumour volumes were measured every 3–5 days with the digital calliper. Mice were randomised in therapy and control groups when tumour size reached 100+/−20 mm3. Animals in the 4 therapy groups were treated with 5 mg/kg KG leflunomid (group 1), 10/5/2,5 mg/kgKG A 771726 (group 2/3/4) by intraperitoneal injection (i.p.). The control group received PBS. Tumour volume was measured every third day with a digital calliper. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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