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Chemotherapy of salivary gland carcinomas with tyrosine kinase inhibitors

Research Project

Project/Area Number 11671869
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionOsaka University (2000)
The University of Tokushima (1999)

Principal Investigator

YURA Yoshiaki  Graduate school of Dentistry Osaka University Professor, 大学院・歯学研究科, 教授 (00136277)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordssalivary gland carcinoma / acidic FGF / growth factor receptor / tyrosine kinase inhibitor
Research Abstract

Chemotherapy is required for the treatment of salivary gland carcinomas, because these tumors recur and metastasize to distant organs frequently. If tumor growth were dependent on the signal of a specific growth factor, interruption of such signal would result in growth inhibition of the tumors. Acidic fibroblast growth factor (aFGF) was been demonstrated in the mouse submandibular gland and was found to stimulate the growth of mouse submandibular gland undifferentiated carcinoma YT-12 cells. Furthermore, bovine brain aFGF promoted the development of 9, 10-dimethyl-1, 2-benzanthracene-induced submandibular gland carcinomas. Since aFGF and FGF receptors were demonstrated in the normal submandibular glands and carcinomas, autocrine and paracrine mechanisms may regulate the growth of the tumors.
Tyrphostins are artificial and low molecular weight compounds that specifically inhibit protein tyrosine kinases. Tyrphostins suppressed the growth of YT-12 cells ; tyrphostin 9 was the most potent inhibitor. Furthermore, the growth of nude mouse tumors induced by YT-12 cell inoculation was suppressed by intra-tumor administration of tyrphostin 9. It also inhibited tyrosine-phosphorylation of membrane proteins including FGF receptor-l in the aFGF-treated YT-12 cells. Flow cytometric analysis, DNA staining with Hochest 33258 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method indicated that tyrpjostin 9 induced the arrest of cell cycle and apoptosis. These results suggest that aFGF play a role in the development of mouse submandibular gland carcinomas, and that tyrosine kinase inhibitor, tyrphostin 9, can be used as an inhibitor for the submandibular gland carcinoma.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Tsujimoto H, et al.: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28(1). 30-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐藤光信 他: "口腔癌におけるUFT+OK-432+RT同時併用療法"Tumor Dormancy Therapy. 1. 17-22 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-teradecanoyl 13-acetate"Intervirology. 43(3). 129-138 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Mental nerve neuropathy as a result of primary herpes simplex virus infection in the oral cavity."Oral Surgery Oral Medicine Oral Pathology Oral radiology Endodontics. 90(3). 306-309 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, et al.: "Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis"Journal of Oral Pathology and Medicine. 30. 159-167 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujimoto H, Yura Y, Yoshioka Y, Kusaka J, Yoshida H, Sato M: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28(1). 30-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato M, Okamoto M, Bando T, Iga H, Yura Y, Yoshida H: "Combined therapy for oral cancer with UFT+OK 432+ RT"Tumor Dormancy Therapy. 1. 17-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Bando T, Yamamoto S, Yoshida H, Sato M: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-teradecanoyl phorbol 13-acetate"Intervirology. 43(3). 129-138 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Kusaka J, Yamakawa R, Bando T, Yoshida H, Sato M: "Mental nerve neuropathy as a result of primary herpes simplex virus infection in the oral cavity."Oral Surgery Oral Medicine Oral Pathology Oral radiology Endodontics. 90(3). 306-309 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yura Y, Yoshioka Y, Yamamoto S, Kusaka J, Bando T, Yoshida H, Sato M: "Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis"Journal of Oral Pathology and Medicine. 30. 159-167 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujimoto H et al.: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28. 30-36 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 由良義明: "ヘルペスウイルスの細胞外放出に対するサイトカラシンDの促進作用"口腔組織培養学会誌. 8・1. 47-48 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐藤光信 他: "口腔癌におけるUFT+OK-432±RT同時併用療法"Tumor Dormacy Therapy. 1. 17-22 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 由良義明: "口腔顔面領域におけるαヘルペスウイルス感染症"日本臨床. 58・4(印刷中). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura Y: "Enhancing effect of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogensis"J Oral Pathol and Med,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yura Y: "Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-o-detradecanoyl phorbol 13 acetate : association with the reorganization of actin filaments and cell motility."Intervirology. 43・3. 129-138 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hitoshi Tsujimoto: "Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas"Journal of Oral Pathology and Medicine. 28. 30-36 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 由良義明: "ヘルペスウイルスの細胞外放出に対するサイトカラシンDの促進作用"口腔組織培養学会誌. 8・1. 47-48 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤光信: "口腔癌におけるUFT+OK-432+RT同時併用療法"Tumor Dormancy Therapy. 1. 17-22 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 由良義明: "口腔顔面領域におけるαヘルペスウイルス感染症"日本臨床. 58・4(印刷中). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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