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

在130个乳腺癌，70种胃癌，94个结肠癌和43种胰腺癌中测量了端粒长度和端粒活性。通过Southern印迹分析测量这些肿瘤标本的端粒（末端限制片段）。分别在27％和8％的情况下检测到降低和细长的端粒长度。使用端粒重复扩增方案（TRAP）测定法测量端粒酶活性。在这些规格表面的串行切片的非同位素陷阱分析中，在存在肠道隐窝细胞（肠道干细胞）的部分中发现了端粒酶活性。在癌症组织中，在95％的乳腺癌，85％的胃癌，73％的结肠癌，96％的胰腺癌中检测到端粒酶激活或上调。使用35个PCR循环和光密度分析的非同位素陷阱测定表明，与往常相同的敏感性……表明非同位素陷阱测定法对临床检查很有用。尝试使用原位PCR的陷阱测定法进行冷冻切除术。在腹膜传播细胞和癌症的胰腺刷细胞中，表达细胞的端粒酶和非表达细胞共存，端粒酶表达可能与细胞周期相关。在82个通过胃或结肠内窥镜检查获得的乳腺肿瘤的细细胞抽吸细胞和38个涂片样品中，被诊断为诊断为恶性肿瘤的样本中有83％被发现的端粒酶活性。这是端粒酶活性可用于诊断癌细胞的存在。但是，在所有癌细胞中并不总是存在端粒酶激活或上调，但可能会根据癌症的进展获得。那就是使用端粒酶抑制剂的抗癌治疗被认为对晚期癌症有用。但是，对于正常粘膜和造血干细胞的副作用需要容易注意。较少的