1999 Fiscal Year Annual Research Report

テロメラーゼを標的にした慢性関節リウマチの遺伝子治療

Research Project

Project/Area Number	10670412
Research Institution	Hiroshima University
Principal Investigator	前田裕行広島大学, 医学部・附属病院, 助手 (80274075)
Co-Investigator(Kenkyū-buntansha)	檜山桂子広島大学, 医学部, 助手 (60253069)
Keywords	アデノウイルスベクター / アンチセンスRNA / PNAs / hTR / hTRT
Research Abstract	我々は、慢性関節リウマチ滑膜組織ではリンパ球テロメラーゼの活性化を伴っており、テロメラーゼ活性は慢性関節リウマチ関節破壊の重症度と関連することを明らかにした。次いで滑膜組織のテロメラーゼ活性を阻害し滑膜病変を抑制する戦略として、テロメラーゼRNA部分(hTR)に対する相補的配列をもつpeptide nucleic acids(PNAs)を用いる方法と、テロメラーゼのcatalytic domain(hTRT)の塩基配列に対するアンチセンスRNA発現ベクターを用いる方法を試みた。 hTRに対する相補的配列をもつpeptide nucleic acids PNAs(センス、アンチセンス)を作成し、E-B virusで不死化したB-リンパ球(テロメラーゼ活性を持つ)の細胞膜処理後に培地に添加し、1〜7日間培養した後テロメラーゼ活性を測定したがこれまでにテロメラーゼ活性に変化は認められなかった。PNAsのBリンパ球への移行効率に問題があると考えられ、今後の検討課題である。 hTRTのアンチセンスRNA発現アデノウイルスベクターを構築しテロメラーゼ活性を持つ癌細胞株、HeLa,LoVo,A549,SW403,VMRC-LCDの各々に感染させ、1〜7日間培養した後、生細胞率、テロメラーゼ活性を測定した。LoVo,VMRC-LCDにおいては生細胞率が低下したがテロメラーゼ活性の有意な低下はみられず、組み換えアデノウイルスの構造上の問題によるものと考えられその改善が今後の課題である。次いで内因性抗炎症メディエーターのリポコルチン1を発現するアデノウイルスベクターを構築し、A549細胞に感染させて副腎皮質ホルモンに匹敵するプロスタグランジンE2産生抑制効果効果が得られたため、今後慢性関筋リウマチの新しい遺伝子治療戦略としてさらに検討予定である。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Tamabawa K.: "Inhibitory Effects of a Lecithinized Superoxide Dismutase on Bleomycin-induced Pulmonary Fibrosis in Mice."Am.J.Resp.Crit.Care Med..
[Publications] Maeda H.: "A family with cases of adult onset still's disease and psoriatic arthritis."Intern Med. 39. 77-79 (2000)
[Publications] Murakami I.: "p53 Gene mutation 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)
[Publications] Yoshikawa M.: "Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese."Int J Mol Med. 5. 49-53 (2000)
[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)
[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)
[Publications] Konishi F.: "Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma."Hiroshima J Med Sci. 48. 79-89 (1999)
[Publications] Maeda A.: "Expression of transforming growth factor-betal and tumour necrosis factor-alpha in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin."Respirology. 4. 359-363 (1999)
[Publications] Oshima M.: "Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases."Lung. 177. 229-240 (1999)
[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)
[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)
[Publications] Yamanishi Y.: "Dermatomyositis associated with rapidly progressive fatal interstitial pneumonitis and pneumomediastium."Scand J Rheumatol. 28. 58-61 (1999)
[Publications] Hiyama E.: "Rapid detection of MYCN gene amplification and telomerase expression in neuroblastoma."Clin Cancer Res. 5. 601-609 (1999)
[Publications] Ishioka S.: "Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese."Intern Med. 38. 944-947 (1999)
[Publications] Ishioka S.: "Two asymptomatic cases with sarcoidosis demonstrated sequential evolution from radiographic stage I to III within five years."Hiroshima J Med Sci. 48. 101-103 (1999)
[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)
[Publications] Ishioka S.: "New monoclonal antibodies against the epithelioid cells in sarcoid granulomas."Exp Lung Res. 25. 663-670 (1999)
[Publications] Ishioka S.: "Sarcoidosis associated with connective tissue diseases:report of 3 cases."Intern Med. 38. 984-987 (1999)
[Publications] 井出利憲: "がんとテロメア・テロメラーゼ."南山堂. 131 (1999)
[Publications] 檜山桂子: "テロメア,テロメラーゼ."日本医学館. 257 (1999)

1999 Fiscal Year Annual Research Report

テロメラーゼを標的にした慢性関節リウマチの遺伝子治療

Principal Investigator

前田 裕行 広島大学, 医学部・附属病院, 助手 (80274075)

Research Products

[Publications] Tamabawa K.: "Inhibitory Effects of a Lecithinized Superoxide Dismutase on Bleomycin-induced Pulmonary Fibrosis in Mice."Am.J.Resp.Crit.Care Med..

[Publications] Maeda H.: "A family with cases of adult onset still's disease and psoriatic arthritis."Intern Med. 39. 77-79 (2000)

[Publications] Murakami I.: "p53 Gene mutation 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)

[Publications] Yoshikawa M.: "Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese."Int J Mol Med. 5. 49-53 (2000)

[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)

[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)

[Publications] Konishi F.: "Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma."Hiroshima J Med Sci. 48. 79-89 (1999)

[Publications] Maeda A.: "Expression of transforming growth factor-betal and tumour necrosis factor-alpha in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin."Respirology. 4. 359-363 (1999)

[Publications] Oshima M.: "Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases."Lung. 177. 229-240 (1999)

[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)

[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)

[Publications] Yamanishi Y.: "Dermatomyositis associated with rapidly progressive fatal interstitial pneumonitis and pneumomediastium."Scand J Rheumatol. 28. 58-61 (1999)

[Publications] Hiyama E.: "Rapid detection of MYCN gene amplification and telomerase expression in neuroblastoma."Clin Cancer Res. 5. 601-609 (1999)

[Publications] Ishioka S.: "Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese."Intern Med. 38. 944-947 (1999)

[Publications] Ishioka S.: "Two asymptomatic cases with sarcoidosis demonstrated sequential evolution from radiographic stage I to III within five years."Hiroshima J Med Sci. 48. 101-103 (1999)

[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)

[Publications] Ishioka S.: "New monoclonal antibodies against the epithelioid cells in sarcoid granulomas."Exp Lung Res. 25. 663-670 (1999)

[Publications] Ishioka S.: "Sarcoidosis associated with connective tissue diseases:report of 3 cases."Intern Med. 38. 984-987 (1999)

[Publications] 井出利憲: "がんとテロメア・テロメラーゼ."南山堂. 131 (1999)

[Publications] 檜山桂子: "テロメア,テロメラーゼ."日本医学館. 257 (1999)

前田裕行広島大学, 医学部・附属病院, 助手 (80274075)