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GENE DIAGNOSIS AND THERAPY OF POORLY DIFFERENTIATED THYROID CARCINOMA.

Research Project

Project/Area Number 06671053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionTOKAI UNIVERSITY

Principal Investigator

ABE Yoshifumi  TOKAI UNIVERSITY DEPARTMENT OF INTERNAL MEDICINE ASSISTANT PROFESSOR, 医学部, 講師 (30124928)

Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Keywordssignal transduction / thyroid carcinoma / growth factor / アポトーシス / 細胞内情報伝達系 / ラス蛋白
Research Abstract

The prognosis of human thyroid carcinoma are usually good, but in some case, especially poorly differentiated carcinoma are fetal. There is no good indicator which predicate the prognosis of thyroid carcinoma. In this project we found that the ras p21 protein are overexposed differentiated carcinoma and some cancer has the mutation of ras oncogene. Hepatocyte growth factor (HGF) simulated p21 protein and increased the phospholylated of Grab and PI3-kinase. In the case of differentiated thyroid carcinoma cells, HGF-induced cell motility was observed only in a low-density culture. On the other hand, in the case of poorly differentiated thyroid carcinoma cells, HGF-induced cell motility was observed not only in a low-density cultures but also in a high-density cultures. HGF increased the tyrosine phosphorylation of p125FAK,which has been shown to correlate with focal adhesion. This phosphorylation was inhibited by herbimycin A,which also blocked the cell motility response. These data suggest that HGF plays important role in the invasive phenotype of thyroid cancers. In cases of primary specimen of papillary carcinoma with recurrence, all 10 cases strongly expressed c-Met which is the receptor of HGF.Apoptosis appears to play important roles in physiological and pathological processes of the endocrine system. We showed that TSH has an inhibitory effect on apoptosis of thyroid cells via the TSH-cyclic AMP pathway and ECM regulates apoptotic cell death of malignant thyroid cells through an integrin-dependent regulation of ICE activity. It was possible that c-Met promoted cell growth and regulated the first step of oncogenesis of the thyroid. Therefore, we suggest that c-Met is a significant prognostic factor of papillary carcinoma. And is may be possible to treated the poorly differentiated thyroid carcinoma by inducing the apoptosis by HGF related signal transaction methods

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 阿部好文: "甲状腺癌の増殖・進展に関与する癌遺伝子" 最新医学. 50. 300-305 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 阿部好文: "甲状腺疾患におけるアポトーシス" 医学のあゆみ. 178. 295-299 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 阿部好文: "甲状腺癌の遺伝子異常" 診断と治療. 85(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Sanno: "Immunohistochemical expression of retinoid X receptor (RXR) isofoems in human pituitaries and pituitary adenomas" Neuroendocrinology. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Y.Noh: "Sympathetic overactivity of intraocular muscles evaluated by accomodation in patients with hyperthyroidism" Thyroid. 6. 289-293 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Abe: "The expression of c-Met protooncogene product in thyroid carcinoma cells and effects of HGF on thyroid cells." Biochem Biophys Res Comm. (in). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Kanamori et al.: "Response of cytosolic free calcium to antiotensin II in individual rat mesangial cells cultured in a medium high in glucose. Hormone and Metabolic" Hormone and Metabolic Research. 11. 561-562 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Abe: "Oncogene in human thyroid carcinoma" Saishin-igaku. 50 (2). 300-306 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Y.Noh et al.: "Sympathetic overactivity of intraocular muscles evaluated by accommodation in patients with hyperthyroidism." Thyroid. 6. 289-293 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Abe: "Apoptosis in thyroid disease" Igakuniayami. 178. 295-299 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Abe: "Onocogen abnormality in human thyroid carcinoma" Shindantochiryou. 85 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Sanno et al: "Immunohistochemical expressiion of retinoid X receptor isoforms in human pituitaries and pituitary adenomas." Neuroendocrinology. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.K.Tani et al.: "Effect of 1a-hydroxyvitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves' disase." Metabolism. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 阿部好文: "甲状腺疾患の診断と治療" イア-ノートSelected Article 1997. 6. 355-369 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 阿部好文: "甲状腺癌の遺伝子異常" 診断と治療. 85・7(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Sanno: "Immunohistochemical expression of retinoid X receptor (RXR) isoforms in human pituitaries and pituitary adenomas" Neuroendocrinology. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Y.Noh: "Sympathetic overactivity of intraocular muscles evaluated by accomodation in patients with hyperthyroidism" Thyroid. 6・4. 289-293 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Abe: "The expression of c-Met protooncogene product in thyroid carcinoma cells and effects of HGF on thyroid cells" Biochem Biophys Res Comm. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 阿部好文: "甲状腺とアポトーシス" 医学のあゆみ. 176(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshifumi Abe: "Expression of the HGF receptor in normal and neoplastic thyroid tissue" Oncogen. 12(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshifumi Abe: "Prognostic value of c-Met expression in papillary thyroid carcinomas" Thyroid. 6(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 阿部好文: "甲状腺癌の増殖・進展に関与する癌遺伝子" 最新医学. 50. 300-306 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 阿部好文: "ras遺伝子とシグナル伝達系" Modern Physcian. 15(in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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