| Project/Area Number |
11671249
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MIZUMOTO Kazuhiro Graduates School of Medical Sciences, Surgery and Oncology KYUSHU UNIVERSITY Research Associate, 医学部・附属病院, 助手 (90253418)
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Moritoshi Otsuka Assay Laboratories, 遺伝子診断センター, センター長
TANAKA Masao Graduates School of Medical Science, Surgery and Oncology KYUSHU UNIVERSITY, 大学院・医学研究院, 教授 (30163570)
MORISAKI Takashi Graduates School of Medical Science, Cancer Therapy and Research KYUSHU UNIVERSITY, 大学院・医学研究院, 助手 (90291517)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | pancreatic cancer / early pancreatic cancer / telomerase |
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| Research Abstract |
To assess the clinical significance of telomerase on the diagnosis and the treatment of pancreatic cancer, telomerase activity was evaluated using telomeric repeat amplification protocol in surgically resected pancreatic tissues and in pancreatic juice.
When the cutoff value was set at 1.00, the positivity rate of telomerase activity in pancreatic cancer tissues was 96.1%, whereas all tissues of adenoma, pancreatitis, normal pancreas and normal pancreatic ducts were negative. We also measured telomerase activity in pancreatic juiced obtained from the patients with pancreatic disorders through balloon catheter inserted into the pancreatic duct with an i.v. injection of secretin. The positive rate of telomerase activity was 83.3% in pancreatic juice from carcinoma patients, whereas only 4.3% was positive in that from adenoma patients. All of pancreatic juice from pancreatitis patients were negative in telomerase activity. The results indicate that measurement of telomerase activity in pancreatic juice may serve as a useful diagnostic tool for the pancreatic cancer.
Since telomerase is specifically activated in pancreatic cancer, telomerase could be a target for the treatment of pancreatic cancer. Telomerase activity was inhibited by the transduction of wild type p53 using recombinant adenovirus, followed by significant apoptosis. 9-Hyroxyellipticine specifically inhibited telomerase activity of pancreatic cancer cells. Meanwhile, the exposure of VP-16 increased telomerase activity. The degree of telomerase activation inversely correlated with the induction of apoptosis. These results suggest that telomerase may have an anti-apoptotic role.
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