• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

MOLECULAR-BIOLOGICAL APPROACHES TO CARCINOGENESIS AND METASTASIS OF HEAD AND NECK CANCER AND THEIR APPLICATIONS TO IMMUNO-GENETIC THERAPY

Research Project

Project/Area Number 13470362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionWAKAYAMA MEDICAL UNIVERSITY

Principal Investigator

YAMANAKA Noboru  Faculty of Medicine Professor, 医学部, 教授 (10136963)

Co-Investigator(Kenkyū-buntansha) TOGAWA Akihisa  Faculty of Medicine Instructor, 医学部, 助手 (70305762)
TAMURA Shinji  Faculty of Medicine Associate Professor, 医学部, 講師 (10244724)
KUKI Kiyonori  Faculty of Medicine Associate Professor, 医学部, 助教授 (40169975)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsHEAD AND NECK CANCER / BETA-CATENIN / APC / VEGF / TNP-470 / SURVIVIN / 頭頚部癌 / Β-カテニン / 癌抑制遺伝子 / カドヘリン / 転移 / 免疫組織染色
Research Abstract

1) Beta-catenin accumulation and the mutation of the beta-catenin gene head and neck cancers were evaluated. Twelve out of 49 (24.5%) cases exhibited beta-catenin accumulation in our histochemical study. The 5 year survival rate was 0% in the beta-catenin accumulation group, compared to 50% in the non-accumulation group, (p<0.01). This finding strongly suggests that beta-catenin may play an important role in the carcinogenesis or progression of head and neck cancer. One of the 15 cases exhibited an APC missense mutation that led to the replacement of amino acids ; this case died in 12 months. Regarding the beta-catein mutation, non of the 31 samples exhibited a gene mutation in beta-catenin exon 3. Thus, the rate of APC and beta-catenin mutation in head and neck cancer may be very low.
2) Vascular endothelial growth factor (VEGF) gene was transfected to the head and neck cancer cell line which lacked the VEGF gene and the effect of gene induction was examined in vitro and in vivo. The m … More axillary cancer cell line which was not expressing VEGF, OKK-LN was established and VEGF gene expressing vector was transfected to OKK-LN cell line and OKK-LN/pCIneo-VEGF which producing VEGF was established. This cell line extensively produced VEGF compared with the control cell line, OKK-LN/pCIneo transfected with pCIneo plasmid alone. Both cell lines were transplanted into 6 week-Balb/c nu/nu mice by subcutaneous injection to right lateral abdomen. Tumor volume of the VEGF-transfected group significantly increased in approximately three times compared with the control group after 35 days of transplantation. The survival of the VEGF-transfected group was shortened by 9 days on an average. The effect on the proliferation of VEGF-producing tumor by TNP-470, Fumagilin analogue, which nonspecifically inhibits angiogenesis was examined. Tumor volume of TNP-470 administered group was significantly reduced to one-third compared with non-administered group after 35 and 42 days of the transplantation. The survival of TNP-470 administered group was significantly prolonged. In conclusion, the production of VEGF may facilitate tumor proliferation, influence the survival, and contribute to the malignancy and the suppression of VEGF may be one of the promising strategies against head and neck cancers.
3) We examined the expression of survivin and the two splicing variants in various cancer cells and normal adult tissues. Two splicing variants were detected in various types of cancer cells as well as survivin. By stimulating peripheral blood lymphocytes with survivin-pulsed antigen-presenting cells, CTLs were successfully induced in vitro from HLA-A24-positive cancer patients. These data suggest that survivin may be a potent T-cell epitope eliciting CTL response against survivin, which is expressed in many kinds of cancer cells. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Hirohashi Y, et al.: "An, HLA-A24-restricted cytotoxic, T-lymphocyte epitope of a tumor-associated protein, survivin"Clin Cancer Res. 8(6). 1731-1739 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 竹井 慎他: "頭頸部癌におけるWintシグナル経路の検討"耳鼻咽喉科免疫アレルギー. 19. 174-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 上野ゆみ他: "頭頸部腫瘍におけるVEGF発現に関する検討"耳鼻咽喉科免疫アレルギー. 19. 176-177 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 竹井 慎他: "頭頸部癌における予後因子としてのβカテニンの過剰発現とAPC遺伝子変量の検討"日本耳鼻咽喉科学会誌. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takei S, et al.: "Roles of beta-catenin overexpression and adenomatous polyposis coli mutation in head and neck cancer"Ninon Jibiinnkouka Gakkai Kaiho. in print. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirohashi Y, et al.: "An HLA-A24-restricted Cytotoxic T Lymphocyte Epitope of a Tumor-associated Protein, Survivin"Clin Cancer Res. 8. 1731-1739 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueno Y, et al.: "Implication of Vascular Endothelial Growth Factor (VEGF) in Head and Neck Cancer"J Jp Immunol Allergol ORL. 19. 176-177 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takei S, et al.: "The Roles of Wnt Signal pathway in Head and Neck Cancer"J Jp Immunol Allergol ORL. 19. 174-175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirohashi Y, et al.: "An HLA-A24-restricted cytotoxic T-lymphocyte epitope of a tumor-associated protein, survivin"Clin Cancer Res. 8(6). 1731-1739 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 竹井慎, 他: "頭頚部癌におけるWintシグナル経路の検討"耳鼻咽喉科免疫アレルギー. 19. 174-175 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 上野ゆみ, 他: "頭頚部癌腫瘍におけるVEGF発現に関する検討"耳鼻咽喉科免疫アレルギー. 19. 176-177 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 竹井慎, 他: "頭頚部癌における予後因子としてのΒカテニンの過剰発現とAPC遺伝子変異の検討"日本耳鼻咽喉科学会誌. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi