{"created":"2024-10-28T08:18:02.696649+00:00","id":2006113,"links":{},"metadata":{"_buckets":{"deposit":"3ac419c1-2537-4d49-9a66-80795088276f"},"_deposit":{"created_by":7,"id":"2006113","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2006113"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02006113","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["1524","609","1250","438"],"control_number":"2006113","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"15-deoxy-Δ12,14-prostaglandin J2の単剤とダサチニブの併用療法は子宮肉腫の増殖を抑制する","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"CYTOTOXIC EFFECT OF 15d-PGJ2 AGAINST UTERINE SALCOMA","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-04-18","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"6","bibliographicPageEnd":"2945","bibliographicPageStart":"2939","bibliographicVolumeNumber":"13","bibliographic_titles":[{"bibliographic_title":"Experimental and Therapeutic Medicine","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC50 determined by MTT assay was 27.41,10.46 and 17.38 μmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC50 was 6.68,17.30 and 6.25 μmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing  AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Spandidos publications","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"© Kawakita et al. This is an open access article distributed under the terms of Creative Commons Attribution License.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"17920981","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"17921015","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA12610820","subitem_source_identifier_type":"NCID"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3021号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2017-03-06"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開：\n内容要旨・審査要旨：LID201705191007.pdf\n論文本文：LID201706261001.pdf\n本論文は，著者TAKAKO KAWAKITAの学位論文として提出され，学位審査・授与の対象となっている。\n著者の申請により要約(2017-05-19公開)に替えて論文全文を公開(2017-06-26)\n学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1325号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.3892/etm.2017.4346"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.3892/etm.2017.4346","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"339206"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"河北, 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KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"abstract","url":"https://tokushima-u.repo.nii.ac.jp/record/2006113/files/LID201705191007.pdf"},"version_id":"e411bd05-c638-4704-877f-45532ac0746f"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2017-06-27"}],"displaytype":"detail","filename":"LID201706261001.pdf","filesize":[{"value":"2.36 MB"}],"format":"application/pdf","licensetype":"license_5","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://tokushima-u.repo.nii.ac.jp/record/2006113/files/LID201706261001.pdf"},"version_id":"19f2dc66-5b30-4882-a4de-aa45d2ca8bc5"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"15‑deoxy‑Δ12,14‑prostaglandin J2","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"uterine sarcoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"dasatinib","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"MAPK","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ERK","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"AKT","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1716268551628"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-01-29"},"publish_date":"2019-01-29","publish_status":"0","recid":"2006113","relation_version_is_last":true,"title":["Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2025-02-10T07:19:15.535449+00:00"}