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Thyroid Cancer Gene Therapyt with Molecular Targeting by Radio-responsing genes

Research Project

Project/Area Number 12470221
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNAGASAKI UNIVERSITY

Principal Investigator

YAMASHITA Shunichi  NAGASAKI UNIVERSITY, Department of Molecular Medicine, Atomic Bomb Disease Institute, Professor, 医学部, 教授 (30200679)

Co-Investigator(Kenkyū-buntansha) OHTSURU Akira  NAGASAKI UNIVERSITY, Department of Molecular Medicine, Atomic Bomb Disease Institute, Assistant Professor, 医学部, 助手 (00233198)
NAMBA Hiroyuki  NAGASAKI UNIVERSITY, Department of Molecular Medicine, Atomic Bomb Disease Institute, Associate Professor, 医学部, 助教授 (80237635)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2000: ¥6,800,000 (Direct Cost: ¥6,800,000)
KeywordsRadiation / Thyroid Cancer / Molecular targeting / polo-like kinase / p53 / HSV-TK / HSP70 / Cre-lox P / Rediation / polo-like Kinase / 甲状腺癌 / 放射線 / 遺伝子治療 / 国際医療協力
Research Abstract

Thyroid follicular cell-derived carcinomas are classified pathologically as differentiated (papillary and follicular) and undifferentiated (anaplastic) carcinoma. Although differentiated carcinoma have relatively good prognosis, anaplastic thyroid carcinoma are highly aggressive and extremely lethal, with poor therapeutic response. External beam radiotherapy with chemotherapy would provide the chance for relative long-terrm survival of patients in thyroid anaplastic carcinoma. The discovery of new potent therapy is urgently warranted. A candidate of this strategy is gene therapy that will be selectively cytotoxic or will increase sensitivity to the ionizing radiationo for anaplastic thyroid cancer. To search the cancer-specific targets, we challenged SAGE screening (DNA Sequence 2000) and PCR-based subtraction (BBCR2001). Among the candidate genes that we found, we focused on radio-inducible hSNK gene which is transcriptionally regulated by p53 binding homology element (BBRC 2001). Next we elucidated a signal transduction pathway specifically induced by ionizing radiation in thyroid cells. It involved PKC-delta that mediates ionizing radiation-induced activation of c-Jun kinase through MKK7 (Oncogene 2001). Finally, we have demonstrated the potential gene therapy approachs in experimental model (Cancer Gene Therapy 2001, Human Gene Therapy 2000).

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (69 results)

All Other

All Publications (69 results)

  • [Publications] 岩松みよ子 他: "温熱療法と癌遺伝子治療"遺伝子医学. 6・1. 36-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Shibata, et al.: "15 years after Chernobyl : new evidence of thyroid cancer"Lancet. 358・9297. 1965-1966 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Shimizu-Yoshida, et al.: "Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells"Biochem Biophys Res Common. 289. 491-498 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Shklyaev, et al.: "Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells"Anticancer Res. 21. 2569-2576 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Sautin, et al.: "Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by irradiation"Thyroid. 10. 733-740 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Mitsutake, et al.: "PKC delta mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells"Oncogene. 20. 989-996 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 三木文夫, 他: "放射線増感効果を応用した新たな肝癌遺伝子治療の開発"長崎医学会雑誌. 75. 276-280 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 難波裕幸: "甲状腺細胞における放射線による細胞内特異的応答の研究"ホルモンと臨床. 49. 179-186 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Shklyaev, et al.: "Sage transcript profiles in cultured human fetal fibroblasts, WI-38"DNA Sequence. 11. 281-286 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Nagayama, et al.: "Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo"J Clin Endocrinol Metab. 85. 4081-4086 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] V.Braiden, et al.: "Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter"Human Gene Therapy. 11. 2453-2463 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Yamashita, et al.: "The Genetics of Complex Thyroid Diseases"Springer-Verlog Tokyo Inc.. 222 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Kuroda, et al: "Distinctive gene expression of receptor-type tyrosine kinase families during rat hepatocarcinogenesis"Int J Mol Med. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Sugiyama, et al: "Aurora-B associated protein phosphatases as negative regulators of kinase activation"Oncogene. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Takamura, et al: "Need for measurement of porphyrins in teardrop in patients with congenital erythropoietic porphyria"Br J Ophthalmol. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Mitsutake, et al: "Tie-2 and Angiopoietin-1 expression in human thyroid tumors"thyroid. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Tsuda, et al: "Role of c-Fyn in FGF-2-mediated tube-like structure formation by murine brain capillary endothelial cells"Biochem Biophys Res Commun. 290. 1354-1360 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Shibata, et al: "15 years after Chernobyl : new evidence of thyroid cancer"Lancet. 358(9297). 1965-1966 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Ishigaki, et al: "Urinary iodine levels and thyroid diseases in children ; comparison between Nagasaki and Chernobyl"Endocrine J. 48. 591-595 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Iwata, et al: "Antologus skin graft transplantation for refractory ulcer hand associated with congenital erythropoietic Porphyria"Plas Reconstr Surg. 108. 1445-1446 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Shimizu-Yoshida, et al: "Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells"Biochem Biophys Res Commun. 289. 491-498 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Shklyaev, et al: "Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells"Anticancer Res. 21. 2569-2576 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Yokota, et al: "Evaluation of a telemedicine system for supporting thyroid disease diagnosis"Medinfo. 10. 866-869 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Morishita, et al: "A 30-base pair element in the first intron of Sox9 acts as an enhancer in ATDC5"Biochem Biophys Res Commun. 288. 347-355 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Kurihara, et al: "Ocular involvement caused by the accumulation of porphyrins in a patient with congenital erythropoietic porphyria"Br J Ophthalmol. 85. 1260 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Takamura, et al: "A new century of international telemedicine for radiation-exposed victims in the world"J Clin Endocrinol Metab. 86. 4000 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Shklyaev, et al: "Transient activation of c-Jun NH2-terminal kinase by growth factors closely links to human thyroid cell survival"Thyroid. 11. 629-636 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Nakayama, et al: "Expression of the ets-1 proto-oncogene in human colorectal carcinoma"Mod Pathol. 14(5). 415-422 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Hamasaki, et al: "The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes"J Gastroenterol. 36. 111-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Nagayama, et al: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53 regulated Cre/loxP system"Cancer Gene Ther. 8. 36-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Mitsutake, H. Namba, S. Shklyaev, T. Tsukazaki, A. Ohtsuru, M. Ohba, T. Kuroki, H. Ayabe, S. Yamashita: "PKC delta mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells"Oncogene. 20. 989-996 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Miura, et al: "Hgs/Hrs, a FYVE domain protein is involved in Smad signaling through cooperation with SARA"Mol Cell Biol. 20. 9346-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Rogounovitch, et al: "Congenital erythropoietic porphyria : a novel homozygous mutation in a Japanese patient"J Invest Dermatol. 15. 1156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Ishihara, et al: "Keloid fibroblasts resist ceramide-induced apoptosis by overexpression of insulin-like growth factor I receptor"J Invest Dermatol. 115. 1065-1071 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Naito, et al: "Overexpression of Ets-1 transcription factor in angiosarcoma of the skin"Pathol Res Pract. 196. 103-109 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Shklyaev, et al: "Sage transcript profiles in cultured human fetal fibroblasts, WI-38"DNA Sequence. 11. 281-286 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] G.A. Thomas, et al: "Thyroid tumor banks"Science. 289o. 2283 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Ohtsuru, et al: "Interdisciplinary approach by hyperthermia and cancer gene therapy"Japan J Hyperthermic Oncol. 16. 131-142 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] V. Braiden, et al: "Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter"Human Gene Therapy. 11. 2453-2463 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Kawashita, et al: "Safe and efficient gene transfer into porcine hepatocytes using Sendai virus-cationic liposomes for bioartificial liver support"Artif Organs. 24. 932]-938 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Akino, et al: "Parathyroid hormone-related peptide is a potent tumor angiogenic factor"Endocrinology. 141. 4313-4316 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Nagayama, et al: "Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo"J Clin Endocrinol Metab. 85. 4081-4086 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Nagayama, et al: "Identification of the sites of asparagine-linked glycosylation on the human thyrotropin receptor and stujdies on their role in receptor function and expression"J Pharmacol Exp Ther. 295. 404-409 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Sautin, et al: "Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by irradiation"Thyroid. 10. 733-740 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Miyazaki, et al: "Dexamethasone inhibition of TGF beta-induced cell growth and type II collagen mRNA expression through ERK-integrated AP-1 activity in cultured rat articular chondrocytes"Osteoarthritis Cartilage. 8. 378-385 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Hoshi, et al: "Radiocesium in children residing in the western districts of the Bryansk oblast from 1991-1996"Health Phys. 79. 182-186 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Nagayama, et al: "Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by p53 in a p53-null thyroid carcinoma cell line in vivo"Anticancer Res. 20. 2723-2728 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Hirota, et al: "Activation of specific MEK-ERK cascade is necessary for TGFb signalin and crosstalk with PKA and PKC pathways in cultured rat articular chondrocytes"Osteoarthritis Cartilage. 8. 241-247 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Takamura, et al: "Chernobyl-induced radiophobia and the incidence of tuberculosis"Lancet. 356. 257 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Yatsugi, et al: "Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis : correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc"J Orthop Sci. 5. 150-156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Ono, et al: "Comparative mapping of seven genes in mouse, rat and Chinese hamster chromosomes by fluorescen ce in situ hybridization"Cytogenet Cell Genet. 89. 209-213 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] I. Morimoto, et al: "Skeltal changes in rats bearing mammosomatotrophic pituitary tumors : a model of acromegaly with gonadal dysfunction"Bone. 26. 255-261 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Ohtsuru, et al: "Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invation activity of fibroblasts in keloid"Endocrine J. 47. S41-S44 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] O. Fofanova, et al: "MR imaging of the pituitary gland in children with confrential combined pituitary hormone deficiency associated with PROP 1 mutations"Am J roentogenol. 174. 555-559 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] E. Nishihara, et al: "Ontogenetic changes in the expression of estrogen receptor alpha and beta in rat pituitary gland detected by immunohistochemistry"Endocrinology. 141. 615-620 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Yamashita, et al: "The Genetics of Complex Thyroid Diseases"Springer-Verlog Tokyo Inc.. 222 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Mitsutake, et al.: "PKC δ mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through Mkk7 in human thyroid cells"Oncogene. 20. 989-996 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Shklyaev, et al.: "Sage transcript profiles in cultured human fetal fibroblasts"DNA Sequence. 11. 281-286 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Shimizu-Yoshida, et al.: "Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells"Biochem Biophys Res Common. 289. 491-498 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] V.Braiden, et al.: "Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter"Human Gene Therapy. 11. 2453-2463 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Nagayama, et al.: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system"Cancer Gene Therapy. 8. 36-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Shibata, et al.: "15 years after Chernobyl : new evidence of thyroid cancer"Lancet. 9297. 1965-1966 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Yamashita, et al.: "The Genetics of Complex Thyroid Diseases"Springer-Verlog Tokyo Inc. 222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Sautin, et al.: "Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by irradiation."Thyroid. 10. 733-740 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Shklyaev, et al.: "Sage transcript profiles in cultured human fetal fibroblasts, WI-38."DNA Sequence. 11. 281-286 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Takamura, et al.: "Chernobyl-induced radiophobia and the incidence of tuberculosis."Lancet. 356. 257 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] G.A,Thomas, et al.: "Thyroid tumor banks."Science. 289. 2283 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Nagayama, et al.: "Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo."J Clin Endocrinol Metab. 85. 4081-4086 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] V.Braiden, et al.: "Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter."Human Gene Therapy. 11. 2453-2463 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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