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1999 Fiscal Year Final Research Report Summary

GENE THERAPY FOR RHEUMATOID ARTHRITIS AIMING TELOMERASE AS A TARGET

Research Project

Project/Area Number 10670412
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

MAEDA Hiroyuki  HIROSHIMA UNIV., MEDICAL HOSPITAL, RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (80274075)

Co-Investigator(Kenkyū-buntansha) HIYAMA Keiko  HIROSHIMA UNIV., FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (60253069)
Project Period (FY) 1998 – 1999
Keywordsadenovirus vector / anti-sense RNA / PNAs / hTR / hTRT
Research Abstract

Telomerase is essential for the indefinite proliferation of human cells. And its activation plays a circle role in cellular immortality. We have shown that detection of telomerase activity in synovial tissues is useful for diagnosis of rheumatoid arthritis (RA). We also have shown that telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA and that the presence of tetomerase activity in RA may be an indicator of an aggressive phenotype.
We evaluated peptide nucleic acids, (PNAS) - mediated inhibition of telomerase activity in various cell lines. The antisense PNAS against a part of telomerase gene demonstrated little inhibitory effect on telomerase activity, indicating that cellular uptake might be a limiting factor.
Next, an adenovirus vector expressing antisense mRNA against a part of telomerase gene was constructed. Telomerase activities in various human cell lines infected with ,the vector were not inhibited. The result indicate that the construct of the vector needs to be further investigated.
Further, an adenovirus vector expressing lipocortin 1, an endogenous anti-inflammation mediator, was constructed. A549 cells infected with the vector showed reduced prostaglandin E2 production, which indicate the vector could mimic a part of actions of corticosteroid. Further exploration for new therapeutic strategy should be continued.

  • Research Products

    (68 results)

All Other

All Publications (68 results)

  • [Publications] Tamagawa K.: "Inhibitory Effects of a Lecithinized Surperoxide Dismutase on Bleomycin-induced pulmonary Fibrosls in Mice"Am.J.Resp.Crit.Care Med..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda H.: "A family with Cases of adult onset still's disease and psoriatic arthritis"Inter Med. 39. 77-79 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami I.: "p53 Gene mutations are asscciated with shortened survival in patients with asvanced non-small cell lung cancer:an analysis of medicall managed patients"Clin Cancer Res. 6. 526-530 (2000)

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

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山英三: "テロメア・テロメラーゼをめぐって"Annual Review呼吸器2000. 30-36 (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 memorv 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] Konishi F.: "Transcriptionally targeted in vivo gene theraty for carcincembrionic antigen-produciong 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.: "Expresstion of transforming growth factor-betal ard tumour necrosis factor-alpha in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal admunistration of bletomycin"Respirology. 4. 356-363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oshima 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 spicing,but not allelic loss,of the FHIT gene increases with development of lunf 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. 513-7 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamanishi Y.: "Dermatomyositis associated with repidly progressive fatal interstitial pneumonitis and pneumomediastinum"Scand Rheumatol. 28. 58-61 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama E.: "Rapid detecticn 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.: "Thicpurine 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.: "Two asymptomatic dases with sarcoidosis demonstrated sequential evolution from radiographic stage I to II within five years"Hiroshima J Med Sci. 48. 101-3 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "A case of group II non-specific interstitial pneumonia developed during corticosteroid therapy after acute respiratory distress syndrome"Respirology. 4. 283-285 (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] Ishioka S.: "Sarcoidosis associated with connective tissue diseases:report of 3 cases"Intern Med. 38. 984-987 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama K.: "Temole,ase activity as a novel marker of lung cancer and immune-associated lung diseases"Int.J.Mol.Med.. 1. 545-549 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S.: "A case of sarcoidosisi with inceased response of peripheral blood mononucleae cells to purified protein derivative antigen depletion of CD8+T cells in vitro"Sarcoidosis Vasculitis and Diffuse Lung Diseases. 15. 194-195 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamanishi Y.: "Telomerase activity in rheumatoid synovium correlates with the monomuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis"J.Rheumatol.. 25. 214-220 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamanishi Y.: "Rheumatoid arthritis associated with diffuse pandronchiolitis"Internal Med. 37. 338-341 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "ヒトの悪性腫瘍におけるテロメラーゼ"炎症と免疫. 6. 53-58 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "テロメラーゼを標的とした抗癌戦略"Molecular Medicine. 35. 1374-1382 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山英三: "悪性腫瘍における「テロメア長」規定因子とその診断的意義"日本臨床. 56. 1139-1145 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "膠原病肺とテロメラーゼ"分子呼吸器病学. 2. 18-24 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "肺癌の腫瘍マーカーとしてのテロメラーゼ活性測定の意義"日本臨床. 56. 1253-1257 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山英三: "膵癌におけるテロメラーゼ"G.I.Research. 6. 137-143 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "肺癌とテロメア・テロメラーゼ"分子呼吸器病学. 2. 233-235 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山英三: "消化器癌に対するテロメラーゼ抑制療法"医学のあゆみ. 184. 907-911 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山桂子: "テロメラーゼ研究の現状"癌と化学療法. 25. 1105-1110 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 檜山英三: "テロメア長と癌診断"消化器科. 27. 245-254 (1998)

    • 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. (1999)

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

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda H, et al: "A family with cases of adult onset still's disease and psoriatic arthritis."Intern Med. 39(12). 77-79 (2000)

    • 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."Clin Cancer Res. 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: "Telomere and telomerase."Annual review on respirology 2000. (Japanese). 30-36 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Haruta H, 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 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: "Two asymtomatic cases with sarcoidosis demonstrated sequential evolution from radiographic stage I to III within five years."Hiroshima J Med Sci. 48. 101-103 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S, et al: "A case of group II non-specific interstitial pneumonia developed during corticosteroid therapy after acute respiratory distress syndrome."Respirology. 4. 283-285 (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 epitheloid 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] Ishioka S, et al: "Sarcoidosis associated with connective tissue diseases : report of 3 cases."Intern Med. 38. 984-987 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Konishi F, et al: "Transcriptionally targetd in vivo gene therapy for carcinoembrionic antigen-producting 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-beta 1 and tumor necrosis factor-alpha 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 disease."Lung. 177. 229-240 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato H: "Alternative splicing, but not allelic loss, of the FHIT gene increase 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 synovial tissue of chronic inflammatory and non-inflammatory rheumatic disease."Int J Mol Med. 4. 513-517 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamanishi Y, et al: "Dermatomyositis associated with rapidly progressive fatal interstitial pneumonitis and pneumomediastinum."Scand J Rheumatol. 28. 58-61 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase activity as a novel marker of lung cancer and immune-associated lung disease."Int J Mol Med. 1(3). 545-549 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S, et al: "A case of sarcoidosis with increased response of peripheral blood mononuclear cells to purified protein derivative antigen after depletion of CD8+T cells in vitro."Sarcoidosis Vasculitis and Diffuse Lung Diseases. 15. 194-195 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamanishi Y, et al: "Telomerase activity in rheumatoid synovium correlates with the monouclear cell infiltration level and disease aggressiveness of rheumatoid arthritis."J Rheumatol. 25(2). 214-220 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamanishi Y, et al: "Rheumatoid arthritis associated with diffuse panbronchiolitis."Internal Med. 37(3). 338-341 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase in human malignant tumors"Inflammation & Immunology (Japanese). 6(6). 605-610 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase as a novel target for anticancer therapy"Molecular Medicine. (Japanese) 35(11). 137-482 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E, et al: "Relationship between telomere length and clinical and biological characteristics of the cancers with telomerase reactivation."Nippon-Rinsho. (Japanese) 56(5). 1139-1145 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase activity in collagen lung"Respiratory Molecular Medicine. (Japanese) 2(2). 18-24 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase activity as a novel marker of lung cancer"Nippon-Rinsho. (Japanese) 56(5). 1253-1257 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E, et al: "Telomerase in pancreatic cancer"G.I. Research. (Japanese) 6(2). 137-143 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomerase and telomerase in lung cancer"Respriatory Molecular Medicine. (Japanese) 2(3). 233-235 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E, et al: "Application of telomerase ingibitors for gastrointestinal cancer therapy"J. Clin. Exp. Med.. (Japanese) 184(12). 907-911 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Advance of research on telomerase"Jpn. J. Cancer Chemother.. (Japanese) 25(8). 1105-1110 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama E, et al: "Telomerase length in digestive organ cancer"Gastroenterology. (Japanese) 27(3). 245-254 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ide T, et al: "Cancer and telomera-telomerase"Nanzan-dow, Tokyo, Japan (Japanese). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama K, et al: "Telomere and telomerase"Nihonigakukan, Tokyo, Japan (Japanese). (1999)

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

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Published: 2001-10-23  

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