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Molecular Analysis of thyroid Cell Apoptosis and Carcinogenesis

Research Project

Project/Area Number 06454340
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionNAGASAKI UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

YAMASHITA Shunichi  NAGASAKI UNIVERSITY SCHOOL OF MEDICINE, ATOMIC DESEASE INSTITUTION, PROFESSOR, 医学部・原研発症予防部門, 教授 (30200679)

Co-Investigator(Kenkyū-buntansha) NAMBA Hiroyuki  NAGASAKI UNIVERSITY SCHOOL OF MEDICINE, ATOMIC DESEASE INSTITUTION, ASSOCIA PROF, 医学部・原研発症予防部門, 助教授 (80237635)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1995: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1994: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsTHYROID / APOPTOSIS / CANCER / RADIATION / INTERNATIONAL COOPERATION / 分子機構
Research Abstract

As a duty of medical research in Nagasaki, Japan, it is essential to concentrate on the radiation-related projects based on the accumulated knowledge and experience of atomic bomb survivors. Especially we have been involved in the Chernobyl Medical Aid Program since 1991 and contributed to the screeming and diagnosis of childhood thyroid diseases around Chernobyl.
To further extend the basic research, especially molecular analysis radiation-induced thyroid tuniorigenesis, we have focused on the critical events of thyroid cell damages induced by radiation escaping from physiological apoptosis, which can eventually induce gene instability and abnormal cell proliferation. The experimental design is compared of in vitro and in vivo thyroid cell differentiation and proliferation regulated by autocrine and paracrine factors in addition to TSH.Among them, TGFbeta is a potent growth-inhibiting cytokine which we demorrtrated the c-myc gene regulation and 5-c-myc-CAT suppression. PTHrP,parathyroid-hormone-related peptide is also another cytokine to be involved on thyroid carcinogenesis, which we confirmed the abnormal expression in various type of thyroid cancer tissues. We have further demonstrated the oncofetal expression of PTHrP in various endocrine tumors and the therapeutic rule of antisense PTHrP oligo nucleotide was confirmed. Point mutations of TSH receptor and ret oncogene are also analyzed in human thyroid tissues. Recently thyroid specific regulation of p53 down stream target genes has been published and a pivotal rule of p53 on thyroid apoptosis and abnormal cell proliferation is confirmed.
Combined with the clinical data published in Thyroid, Int J.Cancer and Health Phys, the new technology of gene hunting such as differential display and SAGE methods is applied in our laboratory. Further studies are planned on clarification of molecular mechanism of thyroid tumorigenesis using in vitro and in vivo experimental systems.

Report

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

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Usa T,etal.: "Correlation between supression of c-myc and antiproliferative effect of transforming growth factor-β1 in thyroid carcinoma cell growth." Endocrinology.135. 1378-1384 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hoshi M,etal.: "Fallout radioactivity in soil and food samples in the Ukraine: Measurements of iodine, plutonium, cesium, and strotium isotopes." Health Phys.67. 187-191 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Namba H,etal.: "Radiation-induced G1 arrest is selectively mediated by the p53-WAD1/Cip1 pathway in human thyroid cells." Cancer Res. 55. 2075-2080 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuda K,etal.: "Automated measurement of urinary iodine with use of ultraviolet irradiation" Clin Chem.41. 581-585 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamashita S,etal.: "Chernobyl and Thyroid." Thyroid. 5. 153-154 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ito M,etal.: "Childhood thyroid disease around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology." Thyroid. 5. 365-368 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamashita S,etal.: "A report on the 1995 Chernobyl Sasakawa project Workshop." Sasakawa medical Health Foundation(in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagataki S,etal.: "Nagasaki Symposium : Radiation and Human Health." Excerpta Medica Congress Series 1103, pl-281 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hoshi M, et al.: "Fallout radioactivity in soil and food samples in the Ukraine : Measurements of iodine, plutonium, cesium, and strotium isotopes" Health Phys.67. 187-191 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Usa T,et al.: "Correlation between supression of c-myc and antiproliferative effect of transforming growth factor-beta1 in thyroid carcinoma cell growth." Endcrine. 135. 1378-1384 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Namba H,et al.: "Radiation-induced G1 arrest is selectively mediated by thep53-WAD1/Cip1 pathway in human thyroid cells." Cancer Res.55. 2075-2080

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuda K,et al.: "Automated measurement of urinary iodine with use of ultraviolet irradiation Clin." Chem.41. 581-585 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamashita S,et al.: "Chernobyl and Thyroid." Thyroid. 5. 153-154 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Uto M,et al.: "Childhood thyroid disease around Chernbyl evaluatedby ultrasound examination and fine needle aspiration cytology." Thyroid. 5. 365-368 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamashita S,et al.: "A report on the 1995 Chernobyl Sasakawa project Workshop." Sasakawa medical Health Foundation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagataki S,et al.: "Nagasaki Symposium : Radiation and Human Health." Excerpta Medica Congress Series. 1103. 1-281 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakashima M et al: "Expression of parathyroid hormone-related peptide in human thyroidtumors" J Pathol. 175. 227-236 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nagataki S et al: "Parathyroid hormone-relatedpeptide expression in endocrine tumors." Miner Electolyte Metab. 21. 148-151 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hosoda C et al: "Establishment and characterization of a malignant epitheloid hemangioendothelioma from mouse thyroidtumor." Endocrine J. 42. 341-350 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Maeda S et al: "A single missense mutation in codon 918 of the RET proto-oncogene in sporadic medulllary thyroid carcinomas." Endocrine J. 42. 245-250 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Namba H et al: "Radiation-induced G1 arrest is selectively mediated by the p53-WAF1/Cip1 pathway in human thyroid cells." Cancer Res. 55. 2075-2080 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matuso T et al: "Inhibition of epidermal growth factor binding system by ionizing radiation in A431 human squamous carcinoma cells." Cancer Lett. 89. 153-159 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamashita S et al: "Role of parathyroid hormone-related peptide in the pathogenesis on pituitary adenomas." Oncogenesis and Molecular Biology on Pituitary tumors, 10 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Melmed S et al: "IGF-1 receptor signalling : Lessons from the somatotroph." Recent Prog Horme Res, 20 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumoto T: "Effects of IL-1 β on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocyte." Ann Rheum Dis. 153. 128-133 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ito M: "Expression of parathyroid hormone-related peptide in relation to perturbations of gastric motility in the rat." Endocrinology. 134. 1936-1942 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akita S: "Thyroid hormone action of rat calvarial sutures." Thyroid. 4. 99-106 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeshita A: "Sequence analysis of the thyrotropin(TSH)receptor gene in congenital primary hypothyrodism associated with TSH unresponsiveness." Thyroid. vol. 255-259 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Usa T: "Correlation between supression of c-myc and antiproliferative effect of transforming growth factor β1 in the thuroid carcinoma cell growth." Endocrinology. 135. 1378-1384 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakasha M: "Expression of parathyroid hormone-related peptide in human thyroid tumors." J.Pathol.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamashita S: "A report on the 1994 Chernobyl Sasakawa Project Workshop." Sasakawa Memorial Health Foundation, 322 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamashita S: "Chernobyl Sasakawa Health and Medical Cooperation-1994.Nagasaki Symposiumon Chernobyl:Update and Future.Nagataki S ed" Elsevier Science, 272 (1994)

    • Related Report
      1994 Annual Research Report

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

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