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The advantage of signal transduction as a translational research in cervical cancer after radiotherapy

Research Project

Project/Area Number 14570885
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionKansai Medical University

Principal Investigator

HARIMA Yoko  Kansai Med.Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (80140276)

Co-Investigator(Kenkyū-buntansha) IMAMURA Masahiro  Kansai Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (40268339)
SOUGAWA Mitsuharu  Kansai Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (10154684)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsCervical carcinoma / Radiotherapy / Predictive marker / Translational Research / Personalized therapy / バイオインフォマティクス
Research Abstract

To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we carried out cDNA microarray experiments on primary cervical cancer comparing with patients in CR group and NC groups. Some of these genes had already been associated with the radiation response, such as XRCC5 which was found more in radioresistant tumors than in radiosensitive ones. Ku80 protein, which is the gene product of XRCC5, using histopathological method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 cervical cancer patients. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses(P=0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive(P=0.04).
Next, to identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method. We compared the expression profiles of thermoradiosensitive and thermoradio-resistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes. We selected 35 genes on the basis of a clustering analysis, arid confirmed the validity of these genes with a cross validation test. Some of these genes were already known to be associated with appptosis(BIK,TEGT,SSI-3), hypoxia-inducible gene(HIF1A,CA12), and tumor cell invasion and metastasis(CTSL,CTSB,PLAU,CD44). We developed a "Predictive Score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant one. These results may eventually lead to the achievement of "personalized therapy" for this disease.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoko Harima: "Prediction of outcome of advanced cervical cancers to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis."Int.J.Radiation Oncology Biol.Phys.. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima: "Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival."The American Journal of Clinical Oncology. 26. e80-e85 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima: "Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy."Int.J.Radiation Oncology Biol.Phys.. 52. 1345-1351 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osamu Kitahara: "Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis."Neoplasia. 4. 295-303 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masahiro Imamura: "Synergistic cell-killing effect of a combination of hyperthermia and heavy ion beam irradiation : In expectation of a breakthrough in the treatment of refractory cancers (Review)."Int.J.Molecular Medicine. 9. 11-18 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsuharu Sougawa: "A case of metastatic bone tumor of missed lung cancer showing unusual manifestations on chest radiogram."Radiation Medicine. 20. 155-158 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima, Akira Togashi, Kenichi Horikoshi, Masahiro Imamura, Mitsuharu Sougawa, Satoshi Sawada, Tatsuhiko Tsunoda, Yusuke Nakamura, Toyomasa Katagiri: "Prediction of outcome of advanced cervical cancers to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis."Int.J.Radiation Oncology Biol.Phys.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima, Satoshi Sawada, Yoshitaka Miyazaki, Kiyonori Kin, Hiroyasu Ishihara, Masahiro Imamura, Mitsuharu Sougawa, Nobuaki Shikata, Takeo Ohnishi: "Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival."The American Journal of Clinical Oncology. 26(4). e80-e85 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masahiro Imamura, Satoshi Sawada, Keizo Harima, Toshiko Shiga, Mitsuharu Sougawa: "Multudetector-row CT analysis of time-dependent changes in lung fields after chest irradiation : Usefulness of precision scans."Oncology Reports. 10. 1449-1454 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima, Satoshi Sawada.Kenji Nagata.Mitsuharu Sougawa, Takeo Ohnishi: "Human papilloma virus(HPV) DNA associated with prognosis of cervical cancer after radiotherapy."Int.J.Radiation Oncology Biol.Phys.. 52(5). 1345-1351 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osamu Kitahara, Toyomasa Katagiri, Tatsuhiko Tsunoda, Yoko Harima, Yusuke Nakamura: "Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis."Neoplasia. 4(4). 295-303 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsuharu Sougawa, Hiroyasu Ishihara, Kenji Nagata, Yoko Harima, Noboru Tanigawa, Sangkil Ha-Kawa, Satoshi Sawada: "A case of metastatic bone tumor of missed lung cancer showing unsual manifestations on chest radiogram."Radiation Medicine. 20(3). 155-158 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masahiro Imamura, Satoshi Sawada, Mika Kasahara-Imamura, Keizo Harima, Kazuki Harada: "Synergistic cell-killing effect of a combination of hyperthermia and heavy ion beam irradiation : In expectation of a breakthrough in the treatment of refractory cancers(Review)."Int.J.Molecular Medicine. 9. 11-18 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Harima: "Prediction of outcome of advanced cervical cancers to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis."Int.J.Radiation Oncology Biol.Phys.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoko Harima: "Hypoxia inducible factor 1A (HIF1A) related to thermoradioresistancy of advanced cervical cancers."Jpn.J.Hyperthermic Oncology. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoko Harima: "Expression of Ku8O in cervical cancer correlates with response to radiotherapy and survival."The American Journal of Clinical Oncology. 26. e80-e85 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masahiro Imamura: "Synergistic cell-killing effect of a combination of hyperthremia and heavy ion beam irradiation : In expectation of a breakthrough in the treatment of refractory cancers."Int.J.Molecular Medicine(Review). 9. 11-18 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mitsuharu Sougawa: "A case of metastatic bone tumor of missed lung cancer showing unsual manifestations on chest radiogram."Radiation Medicine. 20. 155-158 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoko Harima: "Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival"American Journal of Clinical Oncology. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoko Harima: "HLA DQA1^*0103, DQB1^*0601 and DQB1^*03 alleles associated with advanced cervical cancer in Japanese women"International Journal of Cancer. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoko Harima: "Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy"Int. J. Radiation Oncology Biol. Phys.. 52・5. 1345-1351 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osamu Kitahara: "Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis"Neoplasia. 4・4. 295-303 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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