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Analysis of abnormality for check point mechanism regulation by DNA damage with radiation therapy for Oral cancer treatment and molecular target therapy against this mechanism.

Research Project

Project/Area Number 16390592
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionShowa University (2006)
Ehime University (2004-2005)

Principal Investigator

SHINTANI S.  Showa-Univ, Dept.Oral & Maxillofac.Surg., Prof., 歯学部, 教授 (80294429)

Co-Investigator(Kenkyū-buntansha) HAMAKAWA H.  Ehime Univ., Dept.Oral & Maxillofac.Surg., Prof, 医学部教授, 教授 (20127905)
NAKASHIRO K.  Ehime Univ., Dept.Oral & Maxillofac.Surg., A.Prof, 医学部教授, 助教授 (90314880)
HINO S.  Ehime Univ., Dept.Oral & Maxillofac.Surg., A.Prof, 医学部教授, 助手 (90359927)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsOral caner / Molecular target therapy / Radiation / Microarray / Angiogenesis inhibitor / Heat Shock Protein 90 / Cox-2 / EGFR / 化学療法 / p53 / 17-AAG / 放射線治療 / 感受性 / 抵抗性 / Heat shock Protein 90 / EGFR -TK inhibitor / CDK inhibitor / Cox-2 inhibitor / HSP-90 inhibitor
Research Abstract

Radiation therapy continues to remain a major treatment modality for oral cancers. Molecular targeting therapy developed as new molecular approaches derived from the recent increase in the knowledge of cancer biology. A better understanding of cancer biology and in particular of tumor radiation resistance mechanisms led to the identification of new molecular targets that could used to increase the therapeutic ratio of radiation therapy. These approaches attempt to increase specifically tumor radiation response with little impact on normal tissue response. We described the current approach of combined radiation with molecular targeting agents relevant for the treatment of oral cancer. Molecular targeting agents (Inhibitors of EGFR, COX-2, CDK, HSP90 and angiogenesis) enhanced the radio-response of tumors. Because of tumor heterogeneity and the multiple radio-resistance pathways, the responses of tumors were varied. These results suggested that the selection of relevant molecular targeti … More ng agents based on molecular biological information will be necessary for improvement of radiation enhancement.
On the other hand, to determine genes that correlating with radiation sensitivity of oral cancer treatment, we evaluated radiation sensitivity assessed by a standard colony formation assay with a gene microarray system with 7 OSCC cell lines. We found significant associations between dozens of genes expression levels and radiation resistance of OSCC cell lines. We also evaluated the relationship between expression levels of some candidate proteins, i.e. fibroblast growth factor (FGF) 2, friend leukemia inserton (Fli)-1 and an interferon inducible gene 6-16, G1P3, and radiation therapeutic effectiveness in OSCC patients of treated with preoperative radiation therapy. The significant association between the response to preoperative radiation therapy and candidate proteins expressions were observed. These data should contribute useful information for identifying predictive markers for radiation sensitivity, and may lead to the development of alternative treatment modalities for radiation therapy. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2006 2005 2004

All Journal Article (23 results)

  • [Journal Article] P53 dependent radiosensitizing effects of Hsp90 Inhibitor, 17-Allylamino-17-demethoxygeldanamycin on human oral squamous cell carcinoma cell lines.2006

    • Author(s)
      Shintani S, Zhang T., et al.
    • Journal Title

      International Journal of Oncology 29(5)

      Pages: 1111-1117

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.2006

    • Author(s)
      S hintani S, Li C, et al.
    • Journal Title

      Oral Oncology 42(1)

      Pages: 66-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CXCR4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma.2006

    • Author(s)
      Ishikawa T, Nakashiro K, et al.
    • Journal Title

      International Journal of Oncology 28(1)

      Pages: 61-66

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] P53 dependent radiosensitizing effects of Hsp90 Inhibitor, 17-Allylamino-17-demethoxygeldanamycin on human oral squamous cell carcinoma cell lines.2006

    • Author(s)
      Shintani S, Zhang T., Aslam A, Sebastian K, Yoshimura T, Hamakawa H.
    • Journal Title

      International Journal of Oncology 29(5)

      Pages: 1111-1117

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.2006

    • Author(s)
      Shintani 5, Li C, Mihara M, Klosek SK, Terakado N, Hino S, Hamakawa H
    • Journal Title

      Oral Oncology 42(1)

      Pages: 66-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CXCR4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma.2006

    • Author(s)
      Ishikawa T, Nakashiro K, Hara S, Klosek SK, Li C, Shintani S, Hamakawa H
    • Journal Title

      International Journal of Oncology 28(1)

      Pages: 61-66

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] P53 dependent radiosensitizing effects of Hsp90 Inhibitor. 17-Allylamino-17-demethoxygedanamycin on human oral squamous cell carcinoma cell lines.2006

    • Author(s)
      Shinsyoni S, Zhang T. et al.
    • Journal Title

      International Journal of Oncology 29(5)

      Pages: 1111-1117

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.2006

    • Author(s)
      S hintani S, Li C et al.
    • Journal Title

      Oral Oncology 42(1)

      Pages: 66-72

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CXCR4 expression is associated with lymph-node metastasis of oral squamous cell carcinoma.2006

    • Author(s)
      Ishikawa T, Nakashiro K, et al.
    • Journal Title

      International Journal of Oncology. 28(1)

      Pages: 61-66

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 口腔癌切除不能再発症例に対する抗癌剤感受性試験による個別化化学療法の試み2006

    • Author(s)
      新谷悟, 日野聡史他
    • Journal Title

      癌と化学療法 33巻3号

      Pages: 357-360

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.2006

    • Author(s)
      Shintani S, et al.
    • Journal Title

      Oral Oncology 42

      Pages: 66-73

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ヒト口腔扁平上皮癌におけるCDK阻害剤(Flavopiridol)と放射線の併用.2005

    • Author(s)
      三原真理子, 新谷 悟, 他
    • Journal Title

      頭頸部癌 31

      Pages: 34-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CD151 forms a functional complex with c-Met in human salivary gland cancer cells.2005

    • Author(s)
      Klosek SK, Nakashiro K, Hara S, Shintani S. Hasegawa H, Hamakawa H
    • Journal Title

      Biochemical and Biophysical Research Communications 336

      Pages: 408-416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ヒト口腔扁平上皮癌におけるCDK阻害剤(Flavopiridol)と放射線の併用2005

    • Author(s)
      三原 真理子, 新谷 悟, 他
    • Journal Title

      頭頸部癌 31

      Pages: 34-38

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gefitinib ('IRESSA', ZD1839). an epidermal growth factor receptor tyrosine kinase inhibitor, up-regulates P27KIP1 and induces G1 arrest in oral squamous cell carcinoma cell lines.2004

    • Author(s)
      Shintani S, Li C, Mihara M, et al.
    • Journal Title

      Oral Oncology 40

      Pages: 43-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma.2004

    • Author(s)
      Terakado N., Shintani S, et al.
    • Journal Title

      Oral Oncology 40

      Pages: 383-389

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Growth regulated oncogene 1 expression is associated with angiogenesis and lymph node metastasis inhuman oral cancer.2004

    • Author(s)
      Shintani S, Ishikawa T, Nonaka T, Li C, Nakashiro K, Wong DT, Hamakawa H
    • Journal Title

      Oncology 66

      Pages: 316-322

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gefitinib ('IRESSA', ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, up-regulates P27KIP1 and induces G1 arrest in oral squamous cell carcinoma cell lines.2004

    • Author(s)
      Shintani S, Li C, Mihara M, Yano J, Terakado N, Nakashiro K, Hamakawa H
    • Journal Title

      Oral Oncology 40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cyclin G2 dysregulation in human oral cancer.2004

    • Author(s)
      Kim Y, Shintani S, Kohno Y, Zhang R, Wong DT
    • Journal Title

      Cancer Research 64

      Pages: 8980-8986

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma.2004

    • Author(s)
      Terakado N., Shintani S, Yano J, Li C, Mihara M, Nakashiro K, Hamakawa H
    • Journal Title

      Oral Oncology 40

      Pages: 383-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] High Frequency methylation of p16 gene during 4-nitroquinolin 1-oxide-induced rat tongue carcinogenesis.2004

    • Author(s)
      Nakahara Y, Shintani S, Mihara M, Matsumura T, Hamakawa H
    • Journal Title

      Oncology Reports 12

      Pages: 101-106

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma.2004

    • Author(s)
      N Terakado, S Shintani, J Yano, C Li, M Mihara, K Nakashiro, Hamakawa H.
    • Journal Title

      Oral Oncology 40

      Pages: 383-389

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gefinitib, an eppidermal growth factor receptor tyrosine kinase inhibitor, up-regulates p27 and induces G1 arrest in oral squamous cell carcinoma cell2004

    • Author(s)
      S Shintani, C Li, M Mihara, J Yano, N Terakado, K Nakashiro, H Hamakawa.
    • Journal Title

      Oral Oncology 40

      Pages: 43-51

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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