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2001 Fiscal Year Final Research Report Summary

Evaluation of the therapeutic effect of replication-competent adenovirus on thyroid carcinomas

Research Project

Project/Area Number 12671090
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNagasaki University

Principal Investigator

NAGAYAMA Yuji  Nagasaki University, School of Medicine, Department of Pharmacology 1, Associate professor, 医学部, 助教授 (30274632)

Project Period (FY) 2000 – 2001
KeywordsThyroid carcinoma / Gene therapy / replication-competent adenovirus
Research Abstract

We studied the therapeutic effect of the conditionally replication competent adenovirus on thyroid carcinomas in vitro and in vivo.
(1) Differentiated thyroid carcinomas - We constructed the replicative adenovirus (AdTgE1A) in which the E1A gene, an indispensable gene for adenovirus replication, is placed downstream of thyroglobulin (Tg) promoter, a thyroid-specific promoter. Infection of AdTgElA led to E1A expression, virus replication (progeny production) and cytopathic effect in differentiated thyroid carcinoma cells expressing Tg, but not in other cells expressing no Tg. Furthermore, our studies demonstrated the enhanced effect of the combination of AdTgE1A and other gene therapies, including adenoviruses expressing a suicide gene or a cytokine.
(2) Anaplastic thyroid carcinomas - To achieve p53-mutated cell-specific replication of adenovirus, we used "gene inactivation strategy" with p53-responseive promoter, Cre-LoxP system and double infection method. This strategy worked very well in vitro, but not so well in vivo, presumably because of low in vivo infectivity. Construction of a single adenovirus containing all the components was found impossible, since p53 promoter is not absolutely silent in 293 cells.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yuriy Sautin: "Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by irradiation"Thyroid. 10(9). 733-740 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo"J Clin Endocrinol Metab. 85(11). 4081-4086 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Eijun Nishihara: "Ontogenetic changes in the expression of estrogen receptor a and b in rat pituitary gland detected by immunohistochemistry"Endocrinology. 141(2). 615-620 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by wild-type tumor suppressor p53 in xenografts of a p53-null thyroid carcinoma cell line"Anticancer Res.. 20(4). 2723-2728 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yukio Ochi: "Augmentative effect of polyethylene glycol, polyvinyl alcohol and dextran on thyroid-stimulating antibody stimulated cAMP production in FRTL-5 cells and CHO cells expressing human THS receptor"Horm Res.. 53(1). 20-25 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Identification of the sites of asparagine-linked glycosylation on human thyrotropin receptor and studies on their role in the receptor function and expression"J Pharmacol Exp Ther. 295(1). 404-409 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre-loxP system"Cancer Gene Therapy. 8(1). 36-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Stanislav S.Shklyaev: "Transient activation of c-Jun Nh2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes"Thyroid. 11(7). 629-636 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Stanislav S.Shklyaev: "Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells"Anticancer Research. 21(4A). 2569-2576 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lise L.Schwarz-Lauer: "Evidence for a simplified view of autoantibody interactions with the TSH receptor"Thyroid. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing thyrotropin receptor"Journal of Immunology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishihara E., Nagayama Y., Inoue S., Hiroi H., Muramatsu M., Yamashita S., Koji T.: "Ontogenetic changes in the expression of estrogen receptor a and p in rat pituitary gland detected by immunohistochemistry"Endocrinology. 141(2). 615-620 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagayama Y., Shigematsu K., Namba H., Zeki K., Yamashita S., Niwa M.: "Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by wild-type tumor suppressor p53 in xenografts of a p53-null thyroid carcinoma cell line"Anticancer Res.. 20 (4). 2723-2728 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochi Y., Kajita Y., Wu L., Iidaka M., Nagayama Y.: "Augmentative effect of polyethylene glycol, polyvinyl alcohol and dextran on thyroid-stimulating antibody stimulated CAMP production in FRTL-5 cells and CHO cells expressing human TSH receptor"Horm Res.. 53 (1). 20-25 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagayama Y., Nishihara E., Namba H., Yamashita S., Niwa M.: "Identification of the sites of asparagine-linked glycosylation on human thyrotropin receptor and studies on their role in the receptor function and expression"J. Pharmacol. Exp. Ther.. 295 (1). 404-409 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Soutin Y., Takamura N., Shklyaev S., Nagayama Y., Ohtsuru A., Namba H., Yamashita S.: "Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by iiradiation"Thyroid.. 10 (9). 733-740 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagayama Y., Yokoi H., Takeda K., Hasegawa M., Nishihara E., Namba H., Yamashina S., Niwa M.: "Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo."J. Clin Endocrinol. Metab.. 85 (11). 4081-4086 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagayama Y., Nishihara E., Namba H., Yokoi H., Hasegawa M., Mizuguchi H., Hayakawa T., Yamashita S., Niwa M.: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre-LoxP system"Cancer Gene Ther.. 8 (1). 36-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shklyaev SS., Namba H., Mitsutake N., Alipov G., Nagayama Y., Maeda S., Ohtsuru A., Tsubouchi H., Yamashita S.: "Transient activation of c-Jun Nh2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes"Thyroid.. 11 (7). 629-636 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shklyaev SS., Namba H., Suatin Y., Mttsutake N., NagayamaY., Ishikawa N., Ito K., Zeki K., Yamashita S.: "Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells"Anticancer Res.. 21 (4A). 2569-2576 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Schwarz-Lauer LL., Chazenbalk GD., MacLachlan SM., Ochi Y., Nagayama Y., Rapoport B.: "Evidence for a simplified view of autoantibody interactions with the TSH receptor"Thyroid.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagayama Y., Kita-Furuyama M., Nakao K., Ando T., Mizuguchi H., Hayakawa T., Eguchi K., Niwa M.: "A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing thyrotropin receptor"J. Immunol.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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