| Co-Investigator(Kenkyū-buntansha) |
IKE Osamu Kyoto University Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40252514)
MIYATAKE Shin-ichi Kyoto University Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90209916)
SASAI Keisuke Kyoto University Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (20225858)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We applied the cytokinesis-block micronucleus (MN) technique to primary lung cancers to evaluate their biological characteristics. Using this technique, we estimated the fraction of cells undergoing mitosis in vitro (dividing fraction, DF), potential doubling time (T_<pot>) and radiosensitivity (in terms of MN frequency) of human tumors. The assay results for the proliferative activity were compared with the treatment outcome. Tumor tissues were disaggregated to single cells, which were cultured in the presence of cytochalasin B after (or without) radiation. At intervals, the proportion of multinucleate cells (its maximum value is the DF), the average number of nuclei per cell, and micronuclei in binucleate cells were scored. The T_<pot> Was the presumed time for the nuclei/cell ratio to reach 2.0. Of the 71 tumor samples obtained, the DF and T_<pot> were evaluable in 61 (86%) and the MN frequency in 52 (73%). The median DF and T_<pot> values were, respectively, 23% and 7.7 days for ad
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enocarcinoma (N=41 ), 26% and 8.9 days for squamous cell carcinoma (N=13), 27% and 6.5 days for large cell carcinoma (N=3), and 30% aud 7.0 days for small cell carcinoma (N=4). There was no significant difference in the mean DF or T_<pot> values according to the histologic type or disease stage. The mean MN frequency after 2 Gy radiation (minus the 0 Gy frequency) was 0.15 for adenocarcinoma, 0.17 for squamous cell carcinoma, 0.16 for large cell carcinoma, and 0.20 for small cell carcinoma. The MN frequency after radiation was positively correlated with both the DF and the baseline (at 0 Gy) MN frequency. In non-small cell lung cancer, a DF above the median was associated with an increased recurrence rate after operation and the T_<pot> was correlated with the time until relapse in patients who developed recurrence. Although the clinical significance of the MN frequency needs to be clarified in future studies, the DF and T_<pot> determined by this assay appear to be good parameters of tumor proliferative activity. Less
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