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著作: [永澤 秀子]/[宇都 義浩]/Kirk L. Kenneth/[堀 均]/Design of Hypoxia-Targeting Drugs as New Cancer Chemotherapeutics/[Biological & Pharmaceutical Bulletin]

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EID
148480
EOID
710807
Map
0
LastModified
2013年9月8日(日) 19:32:11
Operator
大家 隆弘
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TRUE
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Owner
宇都 義浩
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種別 必須 総説·解説
言語 必須 英語
招待 推奨 依頼
審査 推奨
カテゴリ 推奨 研究
共著種別 推奨
学究種別 推奨
組織 推奨
  1. 徳島大学.工学部.生物工学科.生物機能工学講座
著者 必須
  1. 永澤 秀子(岐阜薬科大学/->個人[紺世 秀子])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 宇都 義浩([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.応用生物資源学分野]/[徳島大学.生物資源産業学部.生物資源産業学科.応用生命講座])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Kirk L. Kenneth
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. 堀 均
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Design of Hypoxia-Targeting Drugs as New Cancer Chemotherapeutics

副題 任意
要約 任意

(英) The tumor microenvironment is now recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also helps define the potential for malignant progression and metastasis. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment. Furthermore, discovery of the hypoxia inducible factor 1alpha (HIF-1alpha) has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. In this paper we give an overview of recent advances in hypoxia research, including cancer treatments that target tumor hypoxia. Progress in the development of hypoxia-targeting drugs will be discussed, including antiangiogenic hypoxic cell radiosensitizers and hypoxic cytotoxins, hypoxia targeting boron carriers and p53-inhibiting bifunctional radiosensitizers. We will also review our own recent research results in these areas. For example, we have found that certain of the 2-nitroimidazole radiosensitizers and heterocycle-N-oxide hypoxic cytotoxins we developed have antiangiogenic activity and antimetastatic activity. We propose that these activities are based on the inhibition of signal transduction mediated by HIF-1alpha. The anti-tumor activities of hypoxia response are considered to be cytostatic (tumor dormancy-inducing) effects in contrast to cytotoxic DNA damaging effects. The combination of these cytostatic effects that are related to radiosensitization with the cytotoxic effects of radiation should improve the prognosis and QOL of patients receiving radiation and lead to an overall response to treatment. Based on these considerations, we developed the antiangiogenic hypoxic cell radiosensitizers, TX-1877, TX-1898 and the hypoxic cytotoxin TX-402 that inhibits the HIF-1alpha pathway We will also discuss our research involved with the development of other drugs to exploit tumor hypoxia, including a hypoxia-targeting boron carrier for boron neutron capture therapy (BNCT) and a p53 inhibiting radiosensitizer.

キーワード 推奨
  1. (英) Angiogenesis Inhibitors
  2. (英) Antineoplastic Agents
  3. (英) Cell Hypoxia
  4. (英) Drug Design
  5. (英) Humans
  6. (英) Radiation-Sensitizing Agents
発行所 推奨
誌名 必須 Biological & Pharmaceutical Bulletin([日本薬学会])
(pISSN: 0918-6158, eISSN: 1347-5215)
ISSN 任意 0918-6158
ISSN: 0918-6158 (pISSN: 0918-6158, eISSN: 1347-5215)
Title: Biological & pharmaceutical bulletin
Title(ISO): Biol. Pharm. Bull.
Supplier: 公益社団法人日本薬学会
Publisher: Pharmaceutical Society of Japan
 (NLM Catalog  (Webcat Plus  (医中誌Web  (J-STAGE  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 29
必須 12
必須 2335 2342
都市 任意
年月日 必須 2006年 12月 初日
URL 任意
DOI 任意 10.1248/bpb.29.2335    (→Scopusで検索)
PMID 任意 17142959    (→Scopusで検索)
NAID 任意
WOS 任意
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: Laboratory of Pharmaceutical Chemistry, Gifu Pharmaceutical University, Japan. hnagasawa@gifu-pu.ac.jp

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

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, N.I.H., Intramural

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

  5. (英) Article.PublicationTypeList.PublicationType: Review

  6. (英) NumberOfReferences: 71