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GENE THERAPY TRIAL FOR XERODERMA PIGMENTOSUM GROUP using xeroderma pigmentosum model mice USING LIPOSMESE.

Research Project

Project/Area Number 11670825
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKyoto University

Principal Investigator

NISHIGORI Chikako  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 講師 (50198454)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsXeroderma Pigmentosum / gene therapy / XPA mice / UDS (unscheduled DNA Synthesis) / Pyrimidine dimers / マウス / XPAモデルマウス / pCHA / pCAGGS
Research Abstract

The purpose of this study is to establish the clinical gene therapy for xeroderma pigmentosum group A.For this purpose, firstly we confirmed if human XPA gene is effective in XPA mice cells, because our goal is gene therapy for XPA patients and we must use XPA model mice before clinical trial. Two plasmids containing human XPA gene, pCAGGS-XPA or pcHA-XPA was transfected by electroporation and the UV induced UDS was measured 24 or 48 hr after UV irradiation. Both pCAGGS-XPA and pcHA-XPA recovered the repair efficiency in XPA mice cells. Cells transfected with pcHA-XPA recovered repair efficiency more completely than those with pCAGGS-XPA.Consequently, pcHA-XPA was used for in vivo study. In in vivo study HVJ (Hemagglutinating Virus of Japan)-liposomes was used for introducing the pcHA-XPA into mice skin, because HVJ-liposomes was already accepted as a useful method for introducing genes with high efficiency. HVJ-liposomes containing pcHA-XPA was injected intradermaly 24 hr before UVB irradiation. 4kJ/m^2 UVB was irradiated at back skin of the mice and UV induced UDS in the epidermal nuclei was measured. UDS of mice injected XPA-HVJ liposmes was higher than that of control liposomes. Recovery of UV induced DNA damage by XPA-HVJ liposomes in vivo was also confirmed by staining the mice skin immunohistochemically using monoclonal antibodies againt pyrimidine dimer and (6-4) photoproduct. Hematozylin-eosin staininig revealed that mice skin injected XPA-HVJ liposomes was less severely damaged by UVB irradiation than that of a control (empty) liposomes.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Miho Matsui,Chikako Nishigori,Sinya Toyokuni et al: "The role of oxidative DNA Damage in Human Arsenic Carcinogenesis : Detection of 8-Hydroxy-2'-Deoxyguanosine in Arsenic-Related Bowmen's Disease"J.Invest.Dermatol. 113. 26-31 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xiao-Li Wang,Kazoko Kita,Chikako Nishigori et al: "Low level of NPM gene expression in UV-sensitive human cell lines."Cancer letters. 153. 183-188 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasuhiro Matsumura,Chikako Nishigori,Yoshiki Miyachi: "Allelic loss at PATCHED gene locus in jaw cyst but not in palmet pit in patients with the Basal cell Nevus Syndrome"Archives.Dermatol.Res.. 292. 475-476 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eriko Otoshi,Yasuhiro Matsumura,Chikako,Nishigori, et al: "Four cases of Dyschromatasis symmetrica hereditaria-Differentiated for xeroderma pigmentosum."Brit.J.Dermatol.. 144. 162-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chikako Nishigori,Yaeno Arima,Miho Matsui, et al: "REPAIR OF OXIDATIVE DNA DAMAGE IN UVB HYPERSENSITIVE DISORDERS"Photomedicine and Photobiology. 22(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miki Tanioka,Akihiko Ikoma,Chikako Nishigori et al: "An autopsy case of angiosaroma : Absence of VE-Cadherin in Primary and Metastic lesions."Brit.J.Dermatol. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 錦織千佳子: "色素性乾皮症の診断と対策"文光堂. 7 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 錦織千佳子: "紫外線と小児皮膚の健康"診断と治療社. 7 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matusi M, Nishigori C, Itoyokuni S, Takada J, Imamura S, Ishikawa M: "The role of oxidative DNA damage ib Human Arsenic Carcinogenesis : Detection of 8-Hydroxyguanosine Arsenic-Related Bowen's Disease"J Invest dermatol. 113. 26-31 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumura Y, Nishigori C, Yagi T, Imamura S Takebe H: "Mutations of p16/p15 Tumor Suppressor Genes and Replication Error Contribute Independently to the Pathogenesis of Sporadic Malignant Melanoma."Archive Dermatol Res. 28. 175-180 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumura Y, Nishigori C, Yagi T, Imamura S, and Takebe: "Chatacterization of molecular defects in xeroderma pigmentosum group F in relation to its H clinically mild symptoms"Hum Mol Genet. 7. 969-974 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishigori C, Yarosh D.B, Shreedhar V, Ullrich S.E, Cox P, Kripke.ML: "Hind III liposomes suppress delayed-type hypersensitivity responses in vivo and production of epidermal IL-10 in vitro"J Immunol. 161. 2684-2691 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chikako Nisigori: "UV-induceed DNA damage in carcinogenesis and its repair"J.Dermatol.Sci. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yagi T, Matsumura Y, Sato M, Nishigori C, Mori, M, Takebe.H: "Complete restoration of normal DNA repair characteristics in Group F xeroderma pigmntosum cells by over-expression of transfected XPF cDNA"Carcinogenesis. 19. 55-60 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miho Matsui,Chikako Nishigori Sinya Toyokuni et al: "The role of oxidative DNA Damage in Human Arsenic Carcinogenesis : Detection of 8-Hydroxy-2′-Deoxyguanosine in Arsenic-Related Bowmen's Disease"J.Inyesr.Dermatol. 113. 26-31 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xiao-Li Wang,Kazoko Kita,Chikako Nishigori et al.: "Low level of NPM gene expression in UV-sensitive human cell lines."Cancer letters. 153. 183-188 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuhiro Matsumura,Chikaki Nishigori,Yoshiki Miyachi: "Allelic loss at PATCHED gene locus in jaw cyst but not in palmer pit in patients with the Basal cell Nevus Syndrome"Archives.Dermatol.Res.. 292. 475-476 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eriko Otoshi,Yasuhiro Matsumura,chiaki Nishigori, et al: "Four cases of Dyschtomarosis symmerrica hereditaria-Differentiated For Xeroderma Digmentosum."Brit.J.Dermatol.. 144. 162-168 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chikako Nishigori,Yaeno Arima,Miho Matsui, et al: "REPAIR OF OXIDATIVE DNA DAMAGE IN UVB HYPERSENSITIVE DISORDERS"Photomedicine and Photobiology. 22(印刷中). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miki Tanioka,Akihiko Ikoma,Chikako Nishigori et al: "An autopsy case of angiosaroma : Absence of VE-Cadherin in Primary and Metastic lesions."Brit.J.Dermatol.. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] 錦織千佳子: "色素性乾皮症の診断と対策"文光堂. 7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 錦織千佳子: "紫外線と小児皮膚の健康"診断と治療社. 7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui M,Nishigori C.,Toyokuni S.,Takada,J.Akaboshi M.Isikawa M,Imamura S.Miyachi Y: "The role of oxidative DNA damage in Human Arsenic Carcinogenesis Detection of 8-Hydoroxy-2'-Deoxyguanosine in Arsenic-Related Bowen's Disease"J.invest.Dermal. 112. 101-106 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishigori C: "UV-induced DNA damage in carcinogenesis and its repair"J.Dermatol.Sci.

    • Related Report
      1999 Annual Research Report
  • [Publications] Takashi Y,Matsumura Y.Sato M,Nishigori C,Mori T,*liber A.Takebe H: "Complete resolution of normal DNA repair characteristics in Group F xeroderma pigmentsum cells by over-expression of transfected XPF cDNA"Carcinogenesis. 19. 55-60 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsumura,Y.,Nishigori,C.Yagi,T.Imamura,S.Takebe,H: "Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms"Hum.Mol.Genet. 7. 969-974 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishigori,C. Yarosn,D.B., Shrealny,V. Ullrich, S.E.Cox, P.Kripke: "HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and production of epidermal IL-10 in vitro"J.Immuno.. 161. 2684-2691 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsumura Y,Nishigori C,Yagi T,Imamura S and Takabe H: "Mutations of p16/p15 Tumor Suppressor Genes and Replication Error Contribute Independently to the Pathogenesis of Sporadic Malignant Melanoma"Archive Dermatol Res. 28. 175-180 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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