Molecular diagnosis of pancreatic cancer by telomerase

端粒酶对胰腺癌的分子诊断

基本信息

批准号：
11671249
负责人：
MIZUMOTO Kazuhiro
金额：
$ 1.98万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671249/
关键词：
pancreatic cancer early pancreatic cancer telomerase

项目摘要

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.

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,胰腺炎，正常胰腺和正常胰管为阴性。我们还测量了通过静脉内插入胰管的球囊导管从胰腺疾病患者获得的胰汁中的端粒酶活性，该患者插入了腹腔管道。注射Sectryin。癌症患者的胰汁的端粒酶活性阳性速率为83.3％，而腺瘤患者的胰酶活性阳性率为4.3％。胰腺炎患者的所有胰汁均为端粒酶活性阴性。结果表明，胰汁中端粒酶活性的测量可能是胰腺癌的有用诊断工具。由于端粒酶在胰腺癌中专门激活，端粒酶可能是治疗胰腺癌的目标。使用重组腺病毒的野生型p53转导抑制端粒酶活性，然后抑制明显的细胞凋亡。 9-羟基胆碱特异性抑制了胰腺癌细胞的端粒酶活性。同时，VP-16的暴露增加了端粒酶活性。端粒酶激活的程度与凋亡的诱导成反比。这些结果表明端粒酶可能具有抗凋亡作用。