Molecular diagnosis of pancreatic cancer by telomerase

为探讨端粒酶在胰腺癌诊断和治疗中的临床意义，应用端粒重复扩增技术对手术切除胰腺组织和胰液中端粒酶活性进行了评价。当截断值为1.00时，端粒酶活性在胰腺癌组织中的阳性率为96.1%，而在腺瘤、胰腺炎、正常胰腺和正常胰管组织中端粒酶活性均为阴性。我们还通过将球囊导管插入胰管并静脉注射分泌素来测量胰腺疾病患者胰液中的端粒酶活性。癌患者胰液端粒酶活性阳性率为83.3%，腺瘤患者胰液端粒酶活性阳性率仅为4.3%。胰腺炎患者的胰液端粒酶活性均为阴性。结果提示，检测胰液端粒酶活性可作为胰腺癌的诊断手段。由于端粒酶在胰腺癌中被特异性激活，端粒酶可能成为胰腺癌治疗的靶点。重组腺病毒转染野生型p53可抑制端粒酶活性，并导致细胞凋亡。9-羟基利匹汀特异性抑制胰腺癌细胞端粒酶活性。同时，暴露于VP-16后端粒酶活性增加。端粒酶活化程度与细胞凋亡诱导呈负相关。这些结果提示端粒酶可能具有抗凋亡作用。

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.