权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

为探讨端粒酶在胰腺癌诊断和治疗中的临床意义，采用端粒重复序列扩增法检测了手术切除的胰腺组织和胰液中端粒酶活性，以1.00为界值时，胰腺癌组织中端粒酶活性阳性率为96.1%，而腺瘤、胰腺炎、正常胰腺和正常胰管均为阴性。我们还检测了胰腺疾病患者胰腺液中端粒酶活性，这些胰腺液是通过将球囊导管插入胰管并静脉注射促胰液素获得的。癌性胰液端粒酶活性阳性率为83.3%，而腺瘤性胰液端粒酶活性阳性率仅为4.3%。胰腺炎患者胰液端粒酶活性均为阴性。结果表明，检测胰液中端粒酶活性可作为胰腺癌的诊断工具，端粒酶在胰腺癌中具有特异性激活，可作为胰腺癌治疗的靶点。用重组腺病毒转导野生型p53可抑制端粒酶活性，随后出现明显的凋亡。9-羟基椭圆藤碱特异性抑制胰腺癌细胞端粒酶活性。同时，VP-16的暴露增加了端粒酶活性。端粒酶的激活程度与细胞凋亡的诱导程度呈负相关。这些结果表明，端粒酶可能具有抗凋亡的作用。