| Budget Amount *help |
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1996: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Research Abstract |
Human somatic cells gradually lose their telomeric repeats each cell division, and telomerase, a ribonucleoprotein which can compensate for the loss of telomeric repeats is considered to elongate cellular lifespan. We have demonstrated that this telomerase is activated not only in immortal cancer cells and germline cells, but also in peripheral lymphocytes, and the level of the activity is upregulated by mitogenic stimulations in vitro. By the present study, we have shown that telomerase activity is useful as a marker for cancer diagnossi and an indicator of biological characteristics for lung cancer, as well as an indicator of clinical aggressiveness of interstitial lung diseases. In surgically resected lung cancer tissues, high telomerase activity was present in all small-cell lung cancers, and correlated with loss of heterozygosity in both p53 and Rb genes but not with tumor size or pathological stage. In a small-cell lung cancer case, detection of telomerase activity in pleural effusion preceded positive finding in cytological analysis. Thus, combination of conventional cytology and telomerase activity analysis was considered to increase the sennsitivity in detecting lung cancer cells.
We also examined telomerase activity in bronchoalveolar (BAL) cells obtained from patients with non-cancerous lung diseases. BAL cells had detectable telomerase activity in 4 out of 76 cases (5.3%). In all these 4 cases, lymphocytes population in BAL cells was increased, 3 of them suffered from collagen diseases, and 2 of them showed poor prognosis. However, sarcoidosis patients with increased number of lymphocytes in BAL cells did not showed detectable telomerase activity, indicating the difference in the mechanism of lymphocyte activation among theses diseases. Telomerase activity in BAL cells may become a novel indicator of disease activity as well as a new target of treatment for interstitial pneumonia.
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