• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2000 Fiscal Year Final Research Report Summary

Gene therapy for cancer targeting telomerase

Research Project

Project/Area Number 11670448
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

ISHIOKA Shinichi  Hiroshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10191868)

Co-Investigator(Kenkyū-buntansha) HIYAMA Keiko  Hiroshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (60253069)
Project Period (FY) 1999 – 2000
Keywordscancer / telomerase / telomere / TRF2 / dominant-negative / apotosis / growth inhibition / hTERT
Research Abstract

Telomerase is essential for the indefinite proliferation of human cells, and is repressed in most normal human somatic cells. So we have tried various strategies of gene therapy for cancer targeting telomerase. First, an adenovirus vector expressing antisense mRNA against a part of telomerase gene, hTERT, was constructed to induce growth inhibition after critical shortening of telomeres. Telomerase activities in various human cell lines, such as HeLa, LoVo, A549, SW403, and VMRC-LCD, infected with the vector were evaluated by TRAP assay. While the viability of the cells decreased in LoVo and VMRC-LCD, telomerase activity was not significantly repressed. Further investigation on the construct of the vector seems to be necessary.
Then we next tried to repress the TRF2 function, which is essential to maintain the D and T loop of telomere structure, by dominant-negative manner, expecting to induce apotosis of cancer cells without delay. We obtained the wild and mutant-TRF2 expressing vectors and introduced them into human cancer cell lines. However, no significant difference in cell proliferation was shown between the wild and dominant negative TRF2 expressing cells. We considered that inactivation of p53 in cancer cell lines may be associated with this result.
From these data, we speculated the possibility that even above strategies were effective for some population, it was not detected by oveall analysis. So we tried to establish the method to evaluate the telomerase activity level in each. By immunohistochemical detection of hTERT expression using anti-hTERT antibody, the telomerase activity in each cell could be evaluated in situ. This method would promote the further investigation to establish the gene therapy targeting telomerase.

  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Hiyama E.: "Immunohistocheical detection of telomerase (hTERT) in human cancer tissues and a subset of cells in normal tissues."Neoplasia. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumagai K.: "Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese"Pharmacogenetics. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E.: "Biological characteristics of neuroblastoma with partial deletion in the short arm of chromosome 1,"Medical and Pediastric Oncology. 36. 67-71 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "Multiple Logistic Regression Analysis of Risk Factors for Development of Steroid-dependent Asthma in Elderly : A comparison with yougner asthmatics"Respiration. 68. 35-40 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami I.: "p53 gene mutations are associated with shortened survival in patients with advanced non-small cell lung cancer: an analysis of medically managed patients"Clinical Cancer Research. 6. 526-530 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshikawa M.: "Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese"Int J Mol Med. 5. 49-53 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E.: "Multifocal Neuroblastoma : Biological Features and Surgical Aspects"Cancer. 88. 1955-1963 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamagawa K.: "Inhibitory effects of a lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis in mice"Am J Respir Crit Care Med. 161. 1279-1284 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mendoza C.: "Allelotype and loss of heterozygosity around the L-myc gene locus in primary lung cancers"Lung cancer. 28. 117-125 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E.: "Telomerase activity as a marker of breast carcinoma in fine-needle aspirated samples"Cancer. 90. 235-238 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "Effects of pranlukast, a cysteinyl leukotriene antagonist, on bronchial responsiveness to methacholine in aspirin-intolerant asthmatics treated with corticosteroids"Hiroshima J Med Sci. 49. 105-108 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "Clinical evaluation of idiopathic interstitial pneumonia and interstitial pneumonia associated with collagen vascular disease using logistic regression analysis."Intern Med. 39. 213-219 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Haruta Y.: "Activation of telomerase is induced by a natural antigen in allergen specific memory T lymphocytes in bronchial asthma"Biochem Biophys Res Commun. 259. 617-623 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E.: "Rapid detection of MYCN gene amplification and telomerase expression in neuroblastoma"Clin Cancer Res. 5. 601-609 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese"Intern Med. 38. 944-947 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "Pranlukast, a cysteinyl leukotriene antagonist, reduces serum eosinophil cationic protein levels in patients with asthma"Hiroshima J Med Sci. 48. 105-110 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "New monoclonal antibodies against the epithelioid cells in sarcoid granulomas"Exp Lung Res. 25. 663-670 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Konishi F.: "Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma"Hiroshima J Med Sci. 48. 79-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda A.: "Expression of transforming growth factor-β1 and tumour necrosis factor-α in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin"Respirology. 4. 359-363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oshiam M.: "Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases"Lung. 177. 229-240 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato H.: "Alternative splicing, but not allelic loss, of the FHIT gene increases with development of lung cancer"Int J Oncol. 15. 81-88 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamanishi Y: "Telomerase activity in the synovial tissues of chronic inflammatory and non-inflammatory rheumatic diseases"Int J Mol Med. 4. 513-517 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井出利憲: "がんとテロメア・テロメラーゼ"南山堂. 131 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "テロメア テロメラーゼ"日本医学館. 257 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E., et al.: "Immunohistocheical detection of telomerase (hTERT) in human cancer tissues and a subset of cells in normal tissues."Neoplasia. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumagai K., et al.: "Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese."Pharmacogenetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E., et al.: "Biological characteristics of neuroblastoma with partial deletion in the short arm of chromosome 1."Medical and Pediastric Oncology. 36. 67-71 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "Multiple Logistic Regression Analysis of Risk Factors for Development of Steroid-dependent Asthma in Elderly : A comparison with yougner asthmatics."Respiration. 68. 35-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami I., et al.: "p53 gene mutations are associated with shortened survival in patients with advanced non-small cell lung cancer : an analysis of medically managed patients."Clinical Cancer Research. 6. 526-530 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikawa M., et al.: "Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese"Int J Mol Med. 5. 49-53 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E., et al.: "Multifocal Neuroblastoma : Biological Features and Surgical Aspects."Cancer. 88. 1955-1963 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamagawa K., et al.: "Inhibitory effects of a lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis in mice."Am J Respir Crit Care Med. 161. 1279-1284 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mendoza C.et al.: "Allelotype and loss of heterozygosity around the L-myc gene locus in primary lung cancers."Lung cancer. 28. 117-125 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E., et al.: "Telomerase activity as a marker of breast carcinoma in fine-needle aspirated samples."Cancer. 90. 235-238 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "Effects of pranlukast, a cysteinyl leukotriene antagonist, on bronchial responsiveness to methacholine in aspirin-intolerant asthmatics treated with corticosteroids."Hiroshima J Med Sci. 49. 105-108 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "Clinical evaluation of idiopathic interstitial pneumonia and interstitial pneumonia associated with collagen vascular disease using logistic regression analysis."Intern Med. 39. 213-219 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Haruta Y., et al.: "Activation of telomerase is induced by a natural antigen in allergen specific memory T lymphocytes in bronchial asthma."Biochem Biophys Res Commun. 259. 617-623 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E., et al.: "Rapid detection of MYCN gene amplification and telomerase expression in neuroblastoma."Clin Cancer Res. 5. 601-609 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese."Intern Med. 38. 944-947 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "Pranlukast, a cysteinyl leukotriene antagonist, reduces serum eosinophil cationic protein levels in patients with asthma."Hiroshima J Med Sci. 48. 105-110 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S., et al.: "New monoclonal antibodies against the epithelioid cells in sarcoid granulomas."Exp Lung Res. 25. 663-670 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Konishi F., et al.: "Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma."Hiroshima J Med Sci. 48. 79-89 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda A., et al.: "Expression of transforming growth factor-β1 and tumour necrosis factor-α in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin."Respirology. 4. 359-363 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oshima M., et al.: "Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases."Lung. 177. 229-240 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato H., et al.: "Alternative splicing, but not allelic loss, of the FHIT gene increases with development of lung cancer."Int J Oncol. 15. 81-88 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamanishi Y., et al.: "Telomerase activity in the synovial tissues of chronic inflammatory and non-inflammatory rheumatic diseases."Int J Mol Med. 4. 513-517 (1999)

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

URL: 

Published: 2002-03-26  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi