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Basic studies for telomerase as a novel target for cancer diganosis and therapy

端粒酶作为癌症诊断和治疗新靶点的基础研究

基本信息

批准号：
08457303
负责人：
HIYAMA Eiso
金额：
$ 3.71万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457303/
关键词：
breast cancer digestive organ cancer telomerase telomere diganosis therapy stem cell basal cell テトメア

项目摘要

Telomere length and telomerase activity were measured in 130 breast cancers, 70 gastric cancers, 94 colonic cancers and 43 pancreatic cancers. Telomere (terminal restriction fragments) lengths of these tumor specimens were measured by Southern blot analysis. Reduced and elongated telomere lengths were detected in 27% and 8%, respectively. Telomerase activity was measured using Telomeric Repeat Amplification Protocol (TRAP) assay. Among noncancerous tissues, telomerase activity was detectable in gastric and colonic mucosal specimens. TRAP assay for serial sections from the surface of these specimens revealed telomerase activity was detectable in the portions where intestinal crypt cells (intestinal stem cells) exist. Among cancer tissues, telomerase activation or upregulation was detected in 95% of breast cancres, 85% of gastric cancers, 73% of colonic cancers, 96% of pancreatic cancers. Non-isotopic TRAP assay using of 35 PCR cycles and densitographic analysis showed the same sensitivi … More ty as usual TRAP assay, indicating the non-isotopic TRAP assay is useful for clinical examination. TRAP assay using of in situ PCR was tried to measure in cryosections. In peritoneal disseminated cells and pancreatic brushing cells of cancer, telomerase expressing cells and non-expressing cells coexisted and telomerase expression was likely to be correlated with cell cycles. In 82 samples of fine needle aspirated cells of breast tumors and 38 smear samples obtained by gastric or colonic endoscopy, 83% of the samples diagnosed as malignancy showed detectable telomerase activity. Thus, telomerase activity was useful for the diagnosis of cancer cell existence. However, telomerase activation or upregulation does not always exist in all cancer cells but is likely to be acquired according to cancer progression. Thus, anticancer therapy using of inhibitors of telomerase is considered to be useful for advanced cancers. However, canful attentions are required for the side effects of normal mucosal and hematopoietic stem cells. Less

对130例乳腺癌、70例胃癌、94例结肠癌和43例胰腺癌进行了端粒长度和端粒酶活性的检测。通过Southern印迹分析测量这些肿瘤标本的端粒（末端限制性片段）长度。端粒长度缩短和延长分别占27%和8%。采用端粒重复序列扩增法（TRAP）检测端粒酶活性。在非癌组织中，胃和结肠粘膜标本端粒酶活性可检测。对这些标本表面的连续切片进行TRAP检测显示，在肠腺细胞（肠干细胞）存在的部分可检测到端粒酶活性。在乳腺癌、胃癌、结肠癌、胰腺癌中，端粒酶活性阳性率分别为95%、85%、73%、96%。非同位素TRAP检测35个PCR循环与光密度分析结果显示，两种方法的敏感性相同。 ...更多信息表明非同位素TRAP法可用于临床检测。用原位PCR方法检测冰冻切片中的TRAP。在腹膜播散细胞和胰腺刷状细胞中，端粒酶表达细胞和非表达细胞共存，端粒酶表达可能与细胞周期有关。在82份乳腺肿瘤细针抽吸细胞样本和38份胃或结肠内窥镜检查获得的涂片样本中，83%诊断为恶性肿瘤的样本显示可检测到端粒酶活性。因此，端粒酶活性可用于诊断癌细胞的存在。然而，端粒酶激活或上调并不总是存在于所有癌细胞中，而是可能根据癌症进展而获得。因此，使用端粒酶抑制剂的抗癌疗法被认为可用于晚期癌症。但对正常粘膜和造血干细胞的副作用需要引起足够的重视。少