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著作: Harada Noboru/[島田 光生]/Okano Shinji/Suehiro Taketoshi/[副島 雄二]/Tomita Yukihiro/Maehara Yoshihiko/IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice/[The Journal of Immunology]

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EID
137767
EOID
685968
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LastModified
2013年5月1日(水) 17:29:29
Operator
大家 隆弘
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島田 光生
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Harada Noboru
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 島田 光生([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.消化器・移植外科学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Okano Shinji
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Suehiro Taketoshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 副島 雄二
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Tomita Yukihiro
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Maehara Yoshihiko
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice

副題 任意
要約 任意

(英) Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p., were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of microvessels and inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice was comparable with that of mIL-12 gene therapy in immunocompetent mice. Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor and elicited the MH134-specific CTL response even under FK506. The dose of FK506 was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12 gene therapy against MH134. Ab-mediated depletion studies suggested that the inhibition of tumor growth, neovascularization, and spontaneous lung metastasis by mIL-12 was dependent almost entirely on NK cells and partially on T cells. These results suggest that intratumoral mIL-12 gene therapy is a potent effective strategy not only to treat recurrences of HCC in liver transplantation, but also to treat solid malignant tumors in immunosuppressed patients with transplanted organ.

キーワード 推奨
  1. (英) Angiogenesis Inhibitors
  2. (英) Animals
  3. (英) Antineoplastic Agents
  4. (英) Carcinoma, Hepatocellular
  5. (英) Cell Line, Tumor
  6. (英) Dose-Response Relationship, Immunologic
  7. (英) Electroporation
  8. (英) Female
  9. (英) Gene Transfer Techniques
  10. (英) Genetic Therapy
  11. (英) Genetic Vectors
  12. (英) Graft Rejection
  13. (英) Growth Inhibitors
  14. (英) Immunosuppressive Agents
  15. (英) Interleukin-12
  16. (英) Killer Cells, Natural
  17. (英) Liver Neoplasms, Experimental
  18. (英) Mice
  19. (英) Mice, Inbred BALB C
  20. (英) Mice, Inbred C3H
  21. (英) Neoplasm Metastasis
  22. (英) Neoplasm Transplantation
  23. (英) Skin Transplantation
  24. (英) T-Lymphocyte Subsets
  25. (英) T-Lymphocytes, Cytotoxic
  26. (英) Tacrolimus
発行所 推奨
誌名 必須 The Journal of Immunology([The American Association of Immunologists])
(pISSN: 0022-1767, eISSN: 1550-6606)
ISSN 任意 0022-1767
ISSN: 0022-1767 (pISSN: 0022-1767, eISSN: 1550-6606)
Title: Journal of immunology (Baltimore, Md. : 1950)
Title(ISO): J Immunol
Publisher: American Association of Immunologists
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 173
必須 11
必須 6635 6644
都市 任意
年月日 必須 2004年 12月 1日
URL 任意 http://www.jimmunol.org/cgi/content/abstract/173/11/6635
DOI 任意
PMID 任意 15557154    (→Scopusで検索)
NAID 任意
WOS 任意 000225307500018
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of, Surgery and Science, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nharada@surg2.med.kyushu-u.ac.jp

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't