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Development of predictive assays for radiosensitivity, chemosensitivit apoptosis, and proliferative activity of tumor and normal tissues

Research Project

Project/Area Number 10557087
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Radiation science
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIBAMOTO Yuta  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (20144719)

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)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
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)
KeywordsPredictive assay / Apoptosis / Micronucleus assay
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 … More 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

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Shibamoto Y 他: "Proliferative activity and micronucleus frequency after radiation of lung cancer cells as assessed by the cytoknesis-block method and their relationships to clinical outcome"Clinical Cancer Research. 4. 677-682 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takagi T Shibamito Y 他: "The influence of DNA ploidy of a human tumor cell line on the frequencies of micronuclei or chromosome aberrations after irradiation"Mutation Research. 418. 49-57 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Guo GZ Sasai K 他: "Simultaneous evaluation of radiation-induced apoptosis and micronuclei in five cell lines"International Journal of Radiation Biology. 73. 297-302 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibamoto Y 他: "Long-term control of multiple lung metasteses from osteosarcoma obtained by conventional radiotherapy ; a case report"Oncology Reports. 6. 1085-1087 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Guo GE Sasai K 他: "A significant correlation between clonogenic radiosensitivity and the simultaneous assessenent of micronucleus and apoptotic cell frequencies"International Journal of Radiation Biology. 75. 857-864 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibamoto Y, Ike O, Mizuno H, Fukuse T, Hitomi H, Takahashi M: "Proliferative activity and micronucleus frequency after radiation of lung cancer cells as assessed by the cytokinesis-block method and their relationship to clinical outcome."Clin Cancer Res. 4. 677-682 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takagi T, Sasai K, Shibamoto Y, Akagi K, Oya N, Shibata T, Kim J, Hiraoka M: "The influence of DNA ploidy of a human tumor cell line on the frequencies of micronuclei or chromosome aberrations after irradiation."Mutat Res. 418. 49-57 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Guo GZ, Sasai K, Oya N, Takagi T, Shibuya K, Hiraoka M: "Simultaneous evaluation of radiation-induced apoptosis and micronuclei in five cell lines."Int J Radiat Biol. 73. 297-302 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibamoto Y, Horii N, Takahashi M: "Long-term control of multiple lung metastases from osteosarcoma obtained by conventional radiotherapy : a case report. Oncol Rep 6 : 1085-1087, 1999"Oncol Rep. 6. 1085-1087 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Guo GZ, Sasai K, Oya N, Shibata T, Shibuya K, Hiraoka M: "A significant correlation between clonogenic radiosensitivity and the simultaneous assessment of micronucleus and apoptotic cell frequencies."Int J Radiat Biol. 75. 857-864 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kokubo M,Shibamoto Y 他: "Efficacy of conventional radiotherapy for recurrent meningioma"Journal of Neuro-Oncology. 48・1. 51-55 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibamoto Y 他: "Intracranial germinoma : radiation therapy with tumor volume-based dose selection"Radiology. 218・2. 452-456 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kokubo M,Shibamoto Y 他: "Long-term results of radiation therapy for pituitary adenoma"Journal of Neuro-Oncology. 47・1. 79-84 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibamoto Y. 他: "Long-term control of multiple lung metastases from osteosarcoma obtained by conventional radiotherapy: a case report"Oncology Reports. 6・5. 1085-1087 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jeremic B.,Shibamoto Y. 他: "Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study"Journal of Clinical Oncology. 17・7. 2092-2099 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Guo GZ.,Sasai K. 他: "A significant correlation between clonogenic radiosensitivity and the simultaneous assessment of micronudeus and apoptotic cell frequencies"International Journal of Radiation Biology. 75・7. 857-864 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuta Shibamoto: "Proliterative activity and micronucleus frequency after radiation of lung cancer cells as assessed by the cytokinesis block method and their relationshin to clinica" Clinical Cancer Research. 4・3. 677-682 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takehisa Takagi: "The influence of DNA ploidy of a human tumer cell line on the froquenctes of micronuclei or chromosome aberrations after irradiation" Mutation Research. 418. 49-57 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuta Shibamoto: "The cytokinesis-block micronucleus assay for the prediction of proliterative activity and radiosensitivity of human tumors" Progress in Radio-Cneology. 6. 509-515 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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