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ncomms7706.pdf | 2.34 MB | Adobe PDF | 見る/開く |
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DCフィールド | 値 | 言語 |
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dc.contributor.author | Hiraoka, Kiriko | en |
dc.contributor.author | Inoue, Takahiro | en |
dc.contributor.author | Taylor, Rhys Dylan | en |
dc.contributor.author | Watanabe, Takayoshi | en |
dc.contributor.author | Koshikawa, Nobuko | en |
dc.contributor.author | Yoda, Hiroyuki | en |
dc.contributor.author | Shinohara, Ken-ichi | en |
dc.contributor.author | Takatori, Atsushi | en |
dc.contributor.author | Sugimoto, Hirokazu | en |
dc.contributor.author | Maru, Yoshiaki | en |
dc.contributor.author | Denda, Tadamichi | en |
dc.contributor.author | Fujiwara, Kyoko | en |
dc.contributor.author | Balmain, Allan | en |
dc.contributor.author | Ozaki, Toshinori | en |
dc.contributor.author | Bando, Toshikazu | en |
dc.contributor.author | Sugiyama, Hiroshi | en |
dc.contributor.author | Nagase, Hiroki | en |
dc.contributor.alternative | 板東, 俊和 | ja |
dc.contributor.alternative | 杉山, 弘 | ja |
dc.contributor.alternative | 永瀬, 浩喜 | ja |
dc.date.accessioned | 2018-04-25T06:00:28Z | - |
dc.date.available | 2018-04-25T06:00:28Z | - |
dc.date.issued | 2015-04-27 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/2433/230862 | - |
dc.description | KRAS遺伝子変異を持ったがんを標的とした新規のアルキル化剤の開発について. 京都大学プレスリリース. 2015-05-01. | ja |
dc.description.abstract | Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively killing tumour cells harbouring KRAS mutations have remained unavailable. Here we demonstrate the direct targeting of KRAS mutant DNA using a synthetic alkylating agent (pyrrole-imidazole polyamide indole-seco-CBI conjugate; KR12) that selectively recognizes oncogenic codon 12 KRAS mutations. KR12 alkylates adenine N3 at the target sequence, causing strand cleavage and growth suppression in human colon cancer cells with G12D or G12V mutations, thus inducing senescence and apoptosis. In xenograft models, KR12 infusions induce significant tumour growth suppression, with low host toxicity in KRAS-mutated but not wild-type tumours. This newly developed approach may be applicable to the targeting of other mutant driver oncogenes in human tumours. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Springer Nature | en |
dc.rights | This is the accepted manuscript of the article, which has been published in final form at https://doi.org/10.1038/ncomms7706 | en |
dc.rights | The full-text file will be made open to the public on 27 October 2015 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. | en |
dc.rights | This is not the published version. Please cite only the published version. | en |
dc.rights | この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 | ja |
dc.subject | Chemical biology | en |
dc.subject | Chemotherapy | en |
dc.subject | Colon cancer | en |
dc.subject | Mutation | en |
dc.title | Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole–imidazole polyamide conjugate | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Nature Communications | en |
dc.identifier.volume | 6 | - |
dc.relation.doi | 10.1038/ncomms7706 | - |
dc.textversion | author | - |
dc.identifier.artnum | 6706 | - |
dc.identifier.pmid | 25913614 | - |
dc.relation.url | https://www.kyoto-u.ac.jp/ja/research-news/2015-05-01 | - |
dcterms.accessRights | open access | - |
datacite.date.available | 2015-10-27 | - |
出現コレクション: | 学術雑誌掲載論文等 |
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