| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○カテゴリ (推奨): |
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 異島 優
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| 2. | (英) Chen D (日) (読)
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| 3. | (英) Fang J (日) (読)
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| 4. | (英) Maeda H (日) (読)
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| 5. | (英) Minomo A (日) (読)
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| 6. | (英) Kragh-Hansen U (日) (読)
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| 7. | (英) Kai T (日) (読)
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| 8. | (英) Maruyama T (日) (読)
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| 9. | (英) Otagiri M (日) (読)
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| ○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 (日)
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| ○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. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Antineoplastic Agents (日) (読)
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| 3. | (英) Cell Death (日) (読)
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| 4. | (英) Colonic Neoplasms (日) (読)
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| 5. | (英) Humans (日) (読)
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| 6. | (英) Mice (日) (読)
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| 7. | (英) Models, Molecular (日) (読)
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| 8. | (英) Neoplasms, Experimental (日) (読)
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| 9. | (英) Nitrosation (日) (読)
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| 10. | (英) Nitroso Compounds (日) (読)
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| 11. | (英) Permeability (日) (読)
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| 12. | (英) Protein Multimerization (日) (読)
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| 13. | (英) Recombinant Proteins (日) (読)
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| 14. | (英) Serum Albumin (日) (読)
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| 15. | (英) Structure-Activity Relationship (日) (読)
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| 16. | (英) Xenograft Model Antitumor Assays (日) (読)
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| ○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 chemistryTitle(ISO): Bioconjug ChemPublisher: American Chemical Society (NLM Catalog)
(Scopus)
(CrossRef)
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| ○巻 (必須): | □ | 23
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| ○号 (必須): | □ | 2
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| ○頁 (必須): | □ | 264 271
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2012年 2月 15日 (平成 24年 2月 15日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1021/bc2005363 (→Scopusで検索)
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| ○PMID (任意): | □ | 22225412 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): |
| ○Scopus (任意): | □ | 2-s2.0-84863147496
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1021/bc2005363 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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