{"_buckets": {"deposit": "55fee11d-32d0-4ee1-a6c8-f08af1d838a6"}, "_deposit": {"id": "51649", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "51649"}, "status": "published"}, "_oai": {"id": "oai:tsukuba.repo.nii.ac.jp:00051649"}, "item_5_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2018-11", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "2", "bibliographicPageEnd": "649", "bibliographicPageStart": "639", "bibliographicVolumeNumber": "110", "bibliographic_titles": [{"bibliographic_title": "Cancer Science"}]}]}, "item_5_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Inactivation of the TP53 tumor suppressor gene is essential during cancer development and progression. Mutations of TP53 are often missense and occur in various human cancers. In some fraction of wild\u2010type (wt) TP53 tumors, p53 is inactivated by upregulated murine double minute homolog 2 (MDM2) and MDM4. We previously reported that simultaneous knockdown of MDM4 and MDM2 using synthetic DNA\u2010modified siRNAs revived p53 activity and synergistically inhibited in vitro cell growth in cancer cells with wt TP53 and high MDM4 expression (wtTP53/highMDM4). In the present study, MDM4/MDM2 double knockdown with the siRNAs enhanced 5\u2010fluorouracil (5\u2010FU)\u2010induced p53 activation, arrested the cell cycle at G1 phase, and potentiated the antitumor effect of 5\u2010FU in wtTP53/highMDM4 human colon (HCT116 and LoVo) and gastric (SNU\u20101 and NUGC\u20104) cancer cells. Exposure to 5\u2010FU alone induced MDM2 as well as p21 and PUMA by p53 activation. As p53\u2010MDM2 forms a negative feedback loop, enhancement of the antitumor effect of 5\u2010FU by MDM4/MDM2 double knockdown could be attributed to blocking of the feedback mechanism in addition to direct suppression of these p53 antagonists. Intratumor injection of the MDM4/MDM2 siRNAs suppressed in vivo tumor growth and boosted the antitumor effect of 5\u2010FU in an athymic mouse xenograft model using HCT116 cells. These results suggest that a combination of MDM4/MDM2 knockdown and conventional cytotoxic drugs could be a promising treatment strategy for wtTP53/highMDM4 gastrointestinal cancers.", "subitem_description_type": "Abstract"}]}, "item_5_publisher_27": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "Wiley"}]}, "item_5_relation_10": {"attribute_name": "PubMed\u756a\u53f7", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "30488540", "subitem_relation_type_select": "PMID"}}]}, "item_5_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1111/cas.13893", "subitem_relation_type_select": "DOI"}}]}, "item_5_rights_12": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 2018 The Authors. Cancer Science published by John Wiley \u0026 Sons Australia, Ltd on behalf of Japanese Cancer Association."}, {"subitem_rights": "This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."}]}, "item_5_select_15": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_5_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1347-9032", "subitem_source_identifier_type": "ISSN"}]}, "item_5_source_id_9": {"attribute_name": "\u66f8\u8a8c\u30ec\u30b3\u30fc\u30c9ID", "attribute_value_mlt": [{"subitem_source_identifier": "AA11808050", "subitem_source_identifier_type": "NCID"}]}, "item_5_subject_20": {"attribute_name": "NII\u30b5\u30d6\u30b8\u30a7\u30af\u30c8", "attribute_value_mlt": [{"subitem_subject": "\u533b\u5b66", "subitem_subject_scheme": "Other"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u5ee3\u702c, \u5145\u660e"}, {"creatorName": "\u30d2\u30ed\u30bb, \u30df\u30c4\u30a2\u30ad", "creatorNameLang": "ja-Kana"}, {"creatorName": "HIROSE, Mitsuaki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "204735", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "30836987", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000030836987"}, {"nameIdentifier": "0000003755", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000003755"}]}, {"creatorNames": [{"creatorName": "\u5175\u982d, \u4e00\u4e4b\u4ecb"}, {"creatorName": "\u30d2\u30e7\u30a6\u30c9\u30a6, \u30a4\u30c1\u30ce\u30b9\u30b1", "creatorNameLang": "ja-Kana"}, {"creatorName": "HYODO, Ichinosuke", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "713", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "60416469", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000060416469"}, {"nameIdentifier": "0000001705", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000001705"}]}, {"creatorNames": [{"creatorName": "Imanishi, Mamiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "212373", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamamoto, Yoshiyuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "212374", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Wang, Xiaoxuan", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "212375", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": 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"path": ["2780/7511", "2780/2180", "3/62/5298/1032"], "permalink_uri": "http://hdl.handle.net/2241/00157078", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_name_i18n": "\u516c\u958b\u65e5", "attribute_value": "2019-07-09"}, "publish_date": "2019-07-09", "publish_status": "0", "recid": "51649", "relation": {}, "relation_version_is_last": true, "title": ["Augmented antitumor activity of 5\u2010fluorouracil by double knockdown of MDM4 and MDM2 in colon and gastric cancer cells"], "weko_shared_id": 5}