| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
In spontaneous chronic pancreatitis model (WBN/Kob rats), pancreatitis was first observed at 12 weeks, and progressed thereafter. By the analysis with RT-PCR, PAP mRNA started to be expressed at 8 weeks, peaked at 12 weeks, and then almost disappeard at 24 weeks. PAP was expressed in the cytoplasm of pancreatic acinar cells by the analysis with in situ hybridization and immunohistochemistry. Expression of cytokines such as TNF-alpha and IL-6 was also studied. TNF-alpha and IL-6 peaked at 8 and 12 weeks, respectively. Drug therapy (camostat mesilate and Saiko-keishi-to) prevented the development of pancreatitis and suppressed the gene expression of PAP and cytokines.
As for apoptosis, the TUNEL method revealed abundant apoptotic inflammatory cells in the stroma of the pancreata of WBN/Kob rats at 12 weeks. However, only a few apoptotic cells were detected in the acini. Anti-apoptotic effets of PAP were suggested in in vitro system using a rat pancreatic acinar AR42J cell line treated wit
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h L-arginine.
Clinical studies on serum PAP in 196 patients with digestive diseases showed that serum PAP was increased in 90% cases of acute pancreatitis, which was significantly higher than the positive rate of 9% in clinically stable chronic pancreatitis. Serum PAP levels were significantly related to the severity of pancreatitis. The elevation of serum PAP prolonged compared to other pancreatic enzymes or CRP, and serum PAP was normalized at the time of clinical healing of acute pancreatitis. The positive rates of serum PAP in gastrointestinal cancers were as follows : gastric cancer 16%, colorectal cancer 40%, hepatocellular carcinoma 40%, biliary tract cancer 26% and pancreatic cancer 40%. Serum PAP was normalized after curative resection of the tumor in 7 cases.
These results suggest that PAP expression is related to the development and progression of chronic pancreatitis and that the action mechanisms of PAP include anti-apoptotic effects. Clinical studies implicate that serum PAP is a useful marker of the severity and healing of acute pancreatitis and that serum PAP is elevated in in cancer cells. Less
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