{"_buckets": {"deposit": "8e44250f-5f97-42d2-865f-7da72a2eaeaf"}, "_deposit": {"id": "8711", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "8711"}, "status": "published"}, "_oai": {"id": "oai:niigata-u.repo.nii.ac.jp:00008711", "sets": ["456", "911"]}, "item_7_alternative_title_1": {"attribute_name": "その他のタイトル", "attribute_value_mlt": [{"subitem_alternative_title": "A Novel EGFR-TKI Resistant Mechanism Based on Intra-tumor heterogeneity"}]}, "item_7_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2015-05", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "5", "bibliographicPageEnd": "234", "bibliographicPageStart": "227", "bibliographicVolumeNumber": "129", "bibliographic_titles": [{"bibliographic_title": "新潟医学会雑誌"}, {"bibliographic_title": "新潟医学会雑誌", "bibliographic_titleLang": "en"}]}]}, "item_7_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "EGFR-TKIは, EGFR遺伝子変異陽性肺癌に対して高い奏効率と長期間の無増悪生存期間を示すが, 治癒に至らしめることはできない. 長期間の無増悪生存期間において生き延びる耐性細胞のメカニズムはほとんど未解明であった. 私達は, 遺伝子変異によらない癌幹細胞化を中心とした intra-tumor heterogeneity がこの初期耐性メカニズムに関わると考え検討を行った. マウスメラノーマ癌幹細胞の網羅的蛋白質解析によりDDX3Xという蛋白質を癌幹細胞特異的蛋白として同定した. 肺癌細胞にDDX3Xを発現させることによりSox2, Snailといった転写因子が up-regulate され, ALDH, CD44など癌幹細胞マーカーの陽性率が上昇する. また, E/N-cadherin スイッチを生じ, EMTが促進されていた. 驚いたことに, EGFR exon19 del という活性型遺伝子変異を有する肺癌細胞は, DDX3Xを発現によりEGFRシグナルをオフとし, β-catenin シグナルをオンとすることで, EGFRシグナル依存性を失う. この結果, EGFR-TKI耐性となっていた. 肺癌組織におけるDDX3X発現を免疫組織化学により検討した結果, EGFR-TKI耐性後にはDDX3Xを高発現する癌細胞が選択され残存していること, EGFR-TKI使用前にDDX3Xを多く発現している場合, 腫瘍縮小が得られにくいことが明らかとなった. 今後, DDX3X RNA helicase inhibitor, β-catenin inhibitor により癌根治を目指した治療の開発を目指す.", "subitem_description_type": "Abstract"}]}, "item_7_full_name_3": {"attribute_name": "著者別名", "attribute_value_mlt": [{"nameIdentifiers": [{"nameIdentifier": "60710", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Kagamu, Hiroshi"}]}, {"nameIdentifiers": [{"nameIdentifier": "60711", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Shoji, Satoshi"}]}, {"nameIdentifiers": [{"nameIdentifier": "60712", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Otsubo, Aya"}]}, {"nameIdentifiers": [{"nameIdentifier": "60713", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Nozaki, Koichiro"}]}, {"nameIdentifiers": [{"nameIdentifier": "60714", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Narita, Ichiei"}]}]}, "item_7_publisher_7": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "新潟医学会"}]}, "item_7_select_19": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_7_source_id_11": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AN00182415", "subitem_source_identifier_type": "NCID"}]}, "item_7_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "00290440", "subitem_source_identifier_type": "ISSN"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "各務, 博"}], "nameIdentifiers": [{"nameIdentifier": "60705", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "庄子, 聡"}], "nameIdentifiers": [{"nameIdentifier": "60706", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "大坪, 亜矢"}], "nameIdentifiers": [{"nameIdentifier": "60707", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "野嵜, 幸一郎"}], "nameIdentifiers": [{"nameIdentifier": "60708", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "成田, 一衛"}], "nameIdentifiers": [{"nameIdentifier": "60709", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-08-06"}], "displaytype": "detail", 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{"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "departmental bulletin paper", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Intra-tumor heterogeneity に基づく新規EGFR-TKI耐性機序の解明", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Intra-tumor heterogeneity に基づく新規EGFR-TKI耐性機序の解明"}, {"subitem_title": "Intra-tumor heterogeneity に基づく新規EGFR-TKI耐性機序の解明", "subitem_title_language": "en"}]}, "item_type_id": "7", "owner": "1", "path": ["456", "911"], "permalink_uri": "http://hdl.handle.net/10191/44067", "pubdate": {"attribute_name": "公開日", "attribute_value": "2016-09-29"}, "publish_date": "2016-09-29", "publish_status": "0", "recid": "8711", "relation": {}, "relation_version_is_last": true, "title": ["Intra-tumor heterogeneity に基づく新規EGFR-TKI耐性機序の解明"], "weko_shared_id": null}