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

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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