{"created":"2023-05-15T14:48:13.511288+00:00","id":66085,"links":{},"metadata":{"_buckets":{"deposit":"fbd21ba7-51fc-4f0b-bf88-7f19b322b183"},"_deposit":{"created_by":1,"id":"66085","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"66085"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00066085","sets":["10:29"]},"author_link":["650722","650729","650732","650728","650734","650731","650715","650724","650725","650730","650733","650717","650723","650716","650718","650726","650719","650720","650727","650721"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2016-09-09","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"放射線治療では、正常組織障害が処方できる腫瘍線量の限界を決めており、正常組織の耐容線量を高める放射線防護剤の開発が期待されている。放射線障害で生じる細胞応答にはp53が深く関与しているため、放射線防護効果を得るための創薬標的分子としてp53は非常に重要である。我々は、p53分子内の亜鉛結合部位を標的とする化合物の合成、探索を進め、p53活性を制御するいくつかの新規放射線防護剤候補化合物を見出した。本研究では、これまでに活性評価された候補化合物の一つ、5-クロロ-8-キノリノール（5CHQ）に注目した。5CHQは、細胞の放射線抵抗性に関わるp53標的遺伝子CDKN1A（遺伝子産物p21）の転写を亢進させ、アポトーシスを促進するp53標的遺伝子BBC3（遺伝子産物 PUMA）を抑制する転写調節作用を示し、これによって培養細胞の放射線細胞死を防ぐという特異な活性を有していた。p21誘導を亢進させるその薬効は、p53の抗細胞死活性を高めるシード化合物として最適と考えられた。そこで、マウス前脚部の骨髄を鉛で遮蔽防護することによって骨髄死を回避する亜全身照射法（sub-total-body irradiation; SBI）によって、腸管障害に対する放射線防護効果を検討したところ、5CHQは、24 Gy-SBIによるマウス腸死を防ぎ、防護活性を示す線量減少率DRF（dose reduction factor）は、骨髄死相当線量の全身照射試験で1.2、腸死相当線量の腹部照射試験で1.3と、新規の放射線防護剤シードとして良好な値を示した。また、21 Gy-SBIマウスの空腸上皮のリアルタイムRT-PCR解析では、Cdkn1a mRNA発現の亢進、およびBbc3 mRNA発現の低下を認め、5CHQは、ヒト培養細胞における作用と同様の作用をマウス腸上皮に対しても示すことが明らかとなった。","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"第25回日本Cell Death学会学術集会","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"森田, 明典"}],"nameIdentifiers":[{"nameIdentifier":"650715","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"高橋, 一平"}],"nameIdentifiers":[{"nameIdentifier":"650716","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"笹谷, めぐみ"}],"nameIdentifiers":[{"nameIdentifier":"650717","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"青木, 伸"}],"nameIdentifiers":[{"nameIdentifier":"650718","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wang, Bing"}],"nameIdentifiers":[{"nameIdentifier":"650719","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有安, 真也"}],"nameIdentifiers":[{"nameIdentifier":"650720","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tanaka, Kaoru"}],"nameIdentifiers":[{"nameIdentifier":"650721","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"澤, 晶子"}],"nameIdentifiers":[{"nameIdentifier":"650722","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"西友, 里恵"}],"nameIdentifiers":[{"nameIdentifier":"650723","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"寺岡, 達郎"}],"nameIdentifiers":[{"nameIdentifier":"650724","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"氏田, 将平"}],"nameIdentifiers":[{"nameIdentifier":"650725","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"谷本圭司"}],"nameIdentifiers":[{"nameIdentifier":"650726","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nenoi, Mitsuru"}],"nameIdentifiers":[{"nameIdentifier":"650727","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"神谷研二"}],"nameIdentifiers":[{"nameIdentifier":"650728","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"永田, 靖"}],"nameIdentifiers":[{"nameIdentifier":"650729","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"細井義夫"}],"nameIdentifiers":[{"nameIdentifier":"650730","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"稲葉俊哉"}],"nameIdentifiers":[{"nameIdentifier":"650731","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"650732","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中 薫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"650733","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井 充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"650734","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"p53標的創薬研究から得られたp53転写調節剤5-クロロ-8-キノリノールの放射線防護作用機構解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"p53標的創薬研究から得られたp53転写調節剤5-クロロ-8-キノリノールの放射線防護作用機構解析"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-01-24"},"publish_date":"2017-01-24","publish_status":"0","recid":"66085","relation_version_is_last":true,"title":["p53標的創薬研究から得られたp53転写調節剤5-クロロ-8-キノリノールの放射線防護作用機構解析"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:52:55.280898+00:00"}