| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
To examine the role of hyperlipidemia in pancreatic carcinogenesis, the effects of anti-hyperlipidemic agents on BOP-induced pancreatic carcinogenesis were investigated in hamsters.
1. Markedly high levels of serum triglycerides and total cholesterol were found in Syrian golden hamsters, but not in C57BL/6 mice, ICR mice, F344 rats and Wistar rats, even at 6 weeks of age Consistent with this finding, LPL activities in the liver were lower in hamsters compared to mice and rats.
2. The effects of pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on LPL expression, serum lipid levels and pancreatic cancer development were examined in hamsters treated with BOP. Pioglitazone treatment elevated LPL mRNA expression in the liver and significantly improved hyperlipidemia. Concurrently, the incidence and multiplicity of pancreatic ductal adenocarcinomas were significantly decreased by pioglitazone in comparison with the controls. These results suggested that suppression
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of pancreatic adenocarcinoma development by pioglitazone is associated with enhanced LPL expression and improvement in the serum lipid profile.
3. The effects of other types of anti-hyperlipidemic agents on BOP-induced hamster pancreatic carcinogenesis were examined by analyzing the ductular proliferation in the pancreas as a surrogate marker for carcinogenesis Bazafibrate, a PPAR ligand, and metformine which improves insulin resistance, were effective in the reduction of BOP-induced ductular proliferation in the pancreas.
4. The sensitivity of pancreatic ductal epithelium to BOP treatment in the model animals for hyperlipidemia was examined. BOP treatment did not affect proliferation of pancreatic ductal epithelium cells in Mongolian gerbils, but slightly increased the proliferation in OLETF rats.
These results indicate that hyperlipidemia could be an enhancing factor for the development of pancreatic cancer in hamsters. However, animals in the hyperlipidemic state were not always sensitive to BOP-induced pancreatic carcinogenesis. Less
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