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2000 Fiscal Year Final Research Report Summary

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
KeywordsXeroderma Pigmentosum / gene therapy / XPA mice / UDS (unscheduled DNA Synthesis) / Pyrimidine dimers
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.

  • Research Products

    (14 results)

All Other

All Publications (14 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
  • [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
  • [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
  • [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
  • [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
  • [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).

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

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      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2002-03-26  

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