{"created":"2025-01-14T01:12:08.031781+00:00","id":2011965,"links":{},"metadata":{"_buckets":{"deposit":"fa9f6809-312b-4bab-9d99-1f56fb76b079"},"_deposit":{"created_by":7,"id":"2011965","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2011965"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02011965","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["936","349","175","852","1572","287"],"control_number":"2011965","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"LansoprazoleはSkp2/p27シグナル伝達経路を介してG1期停止を誘導しsessile serrated lesionsの発生を抑制する","subitem_alternative_title_language":"ja"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2023-11-22","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"23","bibliographicPageStart":"11","bibliographicVolumeNumber":"59","bibliographic_titles":[{"bibliographic_title":"Journal of Gastroenterology","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Although the serrated-neoplasia pathway reportedly accounts for 15%-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from a large series of compounds by employing Connectivity Map (CMAP) analysis of SSL-specific gene expression profiles coupled with in vitro screening using SSL patient-derived organoids (PDOs), and validated their efficacy using a xenograft mouse model of SSL.\nMethods: We generated SSL-specific gene signatures based on DNA microarray data, and applied them to CMAP analysis with 1309 FDA-approved compounds to select candidate compounds. We evaluated their inhibitory effects on SSL-PDOs using a cell viability assay. SSL-PDOs were orthotopically transplanted into NOG mice for in vivo evaluation. The signal transduction pathway was evaluated by gene expression profile and protein expression analysis.\nResults: We identified 221 compounds by employing CMAP analysis of SSL-specific signatures, which should cancel the gene signatures, and narrowed them down to 17 compounds. Cell viability assay using SSL-PDOs identified lansoprazole as having the lowest IC50 value (47 μM) among 17 compounds. When SSL-PDO was orthotopically transplanted into murine intestinal tract, the tumor grew gradually. Administration of lansoprazole to mice inhibited the growth of SSL xenograft whereas the tumor in control mice treated with vehicle alone grew gradually over time. The Ki67 index in xenograft lesions from the lansoprazole group was significantly lower compared with the control group. Cell cycle analysis of SSL-PDOs treated with lansoprazole exhibited a significant increase in G1 phase cell population. Microarray and protein analysis revealed that lansoprazole downregulated Skp2 expression and upregulated p27 expression in SSL-PDOs.\nConclusions: Our data strongly suggest that lansoprazole is the most effective chemopreventive agent against SSL, and that lansoprazole induces G1 cell cycle arrest by downregulating Skp2 and upregulating p27 in SSL cells.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Springer Nature","subitem_publisher_language":"en"},{"subitem_publisher":"Japanese Society of Gastroenterology","subitem_publisher_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"14355922","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"09441174","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA11627089","subitem_source_identifier_type":"NCID"},{"subitem_source_identifier":"AA10988015","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3773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":"2024-02-22"}]},"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本論文は，著者Tomoyuki Kawaguchi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。\nThis version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Natureʼs AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00535-023-02052-0\n学位授与者所属 : 徳島大学大学院医学研究科（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1595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":"10.1007/s00535-023-02052-0"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1007/s00535-023-02052-0","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"404208"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"川口, 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map","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Organoid","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Lansoprazole","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":"Lansoprazole inhibits the development of sessile serrated lesions by inducing G1 arrest via Skp2/p27 signaling pathway","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Lansoprazole inhibits the development of sessile serrated lesions by inducing G1 arrest via Skp2/p27 signaling 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