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著作: [異島 優]/Chen D/Fang J/Maeda H/Minomo A/Kragh-Hansen U/Kai T/Maruyama T/Otagiri M/S-Nitrosated human serum albumin dimer is not only a novel anti-tumor drug but also a potentiator for anti-tumor drugs with augmented EPR effects/[Bioconjugate Chemistry]

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EID
325274
EOID
875281
Map
0
LastModified
2017年11月14日(火) 13:04:16
Operator
大家 隆弘
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TRUE
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0
Owner
異島 優
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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. 異島 優
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Chen D
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Fang J
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Maeda H
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Minomo A
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Kragh-Hansen U
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Kai T
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Maruyama T
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. (英) Otagiri M
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) S-Nitrosated human serum albumin dimer is not only a novel anti-tumor drug but also a potentiator for anti-tumor drugs with augmented EPR effects

副題 任意
要約 任意

(英) Macromolecules have been developed as carriers of low-molecular-weight drugs in drug delivery systems (DDS) to improve their pharmacokinetic profile or to promote their uptake in tumor tissue via enhanced permeability and retention (EPR) effects. In the present study, recombinant human serum albumin dimer (AL-Dimer), which was designed by linking two human serum albumin (HSA) molecules with the amino acid linker (GGGGS)(2), significantly accumulated in tumor tissue even more than HSA Monomer (AL-Monomer) and appearing to have good retention in circulating blood in murine colon 26 (C26) tumor-bearing mice. Moreover, we developed S-nitrosated AL-Dimer (SNO-AL-Dimer) as a novel DDS compound containing AL-Dimer as a carrier, and nitric oxide (NO) as (i) an anticancer therapeutic drug/cell death inducer and (ii) an enhancer of the EPR effect. We observed that SNO-AL-Dimer treatment induced apoptosis of C26 tumor cells in vitro, depending on the concentration of NO. In in vivo experiments, SNO-AL-Dimer was found to specifically deliver large amounts of cytotoxic NO into tumor tissue but not into normal organs in C26 tumor-bearing mice as compared with control (untreated tumor-bearing mice) and SNO-AL-Monomer-treated mice. Intriguingly, S-nitrosation improved the uptake of AL-Dimer in tumor tissue through augmenting the EPR effect. These data suggest that SNO-AL-Dimer behaves not only as an anticancer therapeutic drug, but also as a potentiator of the EPR effect. Therefore, SNO-AL-Dimer would be a very appealing carrier for utilization of the EPR effect in future development of cancer therapeutics.

キーワード 推奨
  1. (英) Animals
  2. (英) Antineoplastic Agents
  3. (英) Cell Death
  4. (英) Colonic Neoplasms
  5. (英) Humans
  6. (英) Mice
  7. (英) Models, Molecular
  8. (英) Neoplasms, Experimental
  9. (英) Nitrosation
  10. (英) Nitroso Compounds
  11. (英) Permeability
  12. (英) Protein Multimerization
  13. (英) Recombinant Proteins
  14. (英) Serum Albumin
  15. (英) Structure-Activity Relationship
  16. (英) Xenograft Model Antitumor Assays
発行所 推奨
誌名 必須 Bioconjugate Chemistry([アメリカ化学会])
(pISSN: 1043-1802, eISSN: 1520-4812)
ISSN 任意 1520-4812
ISSN: 1043-1802 (pISSN: 1043-1802, eISSN: 1520-4812)
Title: Bioconjugate chemistry
Title(ISO): Bioconjug Chem
Publisher: American Chemical Society
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 23
必須 2
必須 264 271
都市 任意
年月日 必須 2012年 2月 15日
URL 任意
DOI 任意 10.1021/bc2005363    (→Scopusで検索)
PMID 任意 22225412    (→Scopusで検索)
CRID 任意
WOS 任意
Scopus 任意 2-s2.0-84863147496
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.1021/bc2005363

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

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