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Development of new measurement methods of tumor oxygenation

Research Project

Project/Area Number 08557057
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

SASAI Keisuke  Kyoto University, Graduate School of Medicine, Associate Professor, Department of Therapeutic Radiology and Oncology, 医学研究科, 助教授 (20225858)

Co-Investigator(Kenkyū-buntansha) FUJIBAYASHI Yasuhisa  Kyoto University, Graduate School of Pharmaceutical Science, Associate Professor, Department of Therapeutic Radiology and Oncology, 薬学研究科, 助教授 (50165411)
HIRAOKA Masahiro  Kyoto University, Graduate School of Medicine, Professor, Department of Therapeutic Radiology and Oncology, 医学研究科, 教授 (70173218)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsHypoxic cell fraction / Comet Assay / Cu-ATSM / chronic hypoxia / acute hypoxia / 低酸素細胞 / Comet Assay法 / DNA障害 / ビスチオセミカルバゾン銅錯体 / 電子伝達系 / ミトコンドリア / ポジトロン / PET
Research Abstract

It is well known that the presence of hypoxic cells in solid tumors is one of the most important cause of failure after radiation therapy and some chemotherapy regimens. Up to this time, many efforts have been made to overcome this problem. However, there is an important problem that we have no valid methods for the routine measurement of the intratumoral hypoxic fraction in patients. Previous study suggests that the hypoxic fraction differs with the tumor type, but it is not known what kind of tumor contains a high hypoxic fraction, that is refractory to strategy for radiotherapy.
In this study, we have tested the possibilities to identify hypoxic fraction in tumors using two methods : the comet assay (single-cell electrophoresis assay) and detection of hypoxic cells using PET scan for Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone).
The comet assay has been developed as a method for measuring DNA damage in single cells after irradiation. We have developed our own methods and image analysis system for the comet assay to identify hypoxic fractions. In vitro, we tested our system using a cultured tumor cell line. In vivo, we compared the hypoxic fractions detected by this assay with those determined by the in vivo-in vitro clonogenic assay using two rodent tumors, which exhibit different types of hypoxia : acute and chronic.
In vitro, our method could differentiate hypoxic cells from oxic cells, using the parameter of tail moment. In vivo, there were good correlations between the hypoxic fractions determined by the comet assay and by the clonogenic assay, in both tumors. By comparison of the two methods in chronically hypoxic and acutely hypoxic tumors, we further confirmed that the comet assay is clinically useful for estimation hypoxic fractions of solid tumors.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [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."Mut Res/Gen.Tox.Env.Mut. 418(1). 49-57 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibata T、Akiyama N、Noda M、Sasai K、Hiraoka M: "Enhancement of gene expression under hypoxic conditions using fragment of the human vascular endothelial growth factor and the erythropoietin genes."Int.J.Radiat.Oncol.Biol.Phys.. 42(4). 913-916 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya K、Sasai K、Xie XJ、Utsumi H、Shibata T、Hiraoka M: "Detection of hypoxic cells in murine tumors using the comet assay:Comparison with a conventional radiobiological assay."Jpn.J.Cancer.Res.. 90(8). 880-886 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya K、Fujibayashi Y、Yoshimi E、Sasai K、Hiraoka M、Welch MJ: "Cytosolic/microsomal redox pathway:a reductive retention mechanism of a PET-oncology tracer,Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone)(Cu-PTSM)."Annals Nuclear Medicine.. 13(5). 287-292 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 笹井啓資、渋谷景子、平岡真寛: "臨床応用可能なプレディクティブ・アッセイ"癌の臨床. 43(2). 163-167 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 渋谷景子、笹井啓資、柴田 徹、平岡真寛、藤林靖久: "腫瘍放射線感受性予測のための腫瘍内低酸素細胞分画測定法の開発"インナービジョン. 13(9). 26 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 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"Mut Res / Gen.Tox. Env.Mut. 418(1). 49-57 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibata T., Akiyama N, Noda M, Sasai K, Hiraoka M: "Enhancement of gene expression under hypoxic conditions using fragment of the human vascular endothelial growth factor and the erythropoietin genes"Int. J. Radiat. Oncol. Brol. Phys.. 42(4). 913-916 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya K, Sasai K, Xie XJ. Utsumi H, Shibata T, Hiraoka M: "Detection of hypoxic cells in murine tumors using the comet assay : Comparison with a conventional radiobiological assay"Jpn. J, Cancer. Res.. 90(8). 880-886 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibuya K, Fujibayashi Y, Yoshimi E, Sasai K, Hiraoka M, Welch MJ: "Cytosolic/microsomal redox pathway : a reductive retention mechanism of a PET-oncology tracer, Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone)(Cu-PTSM)"Annals Nuclear Medicine. 13(5). 287-292 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 渋谷景子、笹井啓資、柴田 徹、平岡真寛、藤林靖久: "腫瘍放射線感受性予測のための腫瘍内低酸素細胞分画測定法の開発" インナービジョン. 13(9). 26 (1998)

    • Related Report
      1998 Annual Research Report
  • [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." Mut Res/gen.tox.Env.mut. 418(1). 49-57 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 笹井啓資: "癌の放射線治療" 金芳堂(京都), pp145-153 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 笹井啓資,渋谷景子 他: "臨床応用可能なプレディクティブ・アッセイ" 癌の臨床. 43(2). 163-167 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasai,K., Murata,R., et al.: "Radiation therapy for ocular choroidal neovascularization (PhaseI/II study) : Preliminary report." Int.J.Radiat.Oncol.Biol.Phys.39(1). 173-178 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Guo G.Z., Sasai,K., et al.: "Simultaneous evaluation of radiation-induced apoptosis and micronucei in five cell lines." Int.J.Radiat.Oncol.Biol.Phys.73(3). 297-302 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shibamoto,Y., Sasai,K., et al.: "Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy." Int.J.Radiat.Oncol.Biol.Phys.37(3). 505-510 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakayama,M., Sasai,K., et al.: "Value of low-dose Gallium-67 imaging in detection of non-Hodgkin's lymphoma recurrence." Radiation Medicine. 15(2). 79-83 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagata,Y., Sasai,K., et al.: "Clinical results of radiofrequency hyperthermia for malignant liver tumors." Int.J.Radiat.Oncol.Biol.Phys.38(2). 359-365 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murata-R.,Hiraoka-M.,et al.: "Changes in cell proliferative parameters of SCCV II and EMT6 murine tumors after single-dose irradiation." Jpn-J-Cancer-Res.87(6). 662-668 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sasaki-K.,et al.: "Non-Hodgkin's lymphama of the thyroid. A clinical study of twenty-two cases." Acta-Oncol.35(4). 457-462 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shibata-T.,Sasaki-K.,Hiraoka-M.,et al.: "Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation." Jpn-J-Cancer-Res.87(1). 98-104 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagata-Y.,Hiraoka-M.,et al.: "Development of an integrated radiotherapy network system." Int-J-Radiat-Oncol-Biol-Phys.34(5). 1105-1111 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Murata-R.,Sasai-K.,et al.: "Reoxygenation after single irradiation in rodent tumors of different types and sizes." Int-J-Radiat-Oncol-Biol-Phys.34(4). 859-865 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishimura-Y.,Hiraoka-M.,et al.: "Combined effects of an angiogenesis inhibitor(TNP-470)and hyperthermia." Br-J-Cancer.73(3). 270-274 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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