{"created":"2023-05-15T09:41:17.724969+00:00","id":384,"links":{},"metadata":{"_buckets":{"deposit":"ae394410-9df9-4e6c-bdfd-168059800b24"},"_deposit":{"created_by":11,"id":"384","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"384"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00000384","sets":["13:40"]},"author_link":["267"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2016-03-24"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"香川大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Kagawa University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"16201","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Human multiple myeloma (MM) is an incurable hematological malignancy for which novel therapeutic agents are needed. Calmodulin (CaM) antagonists have been reported to induce apoptosis and inhibit tumor cell invasion and metastasis in various tumor models. However, the antitumor effects of CaM antagonists on MM are poorly understood. In this study, we investigated the antitumor effects of naphthalenesulfonamide derivative selective CaM antagonists W-7 and W-13 on MM cell lines both in vitro and in vivo.","subitem_description_language":"en","subitem_description_type":"Abstract"},{"subitem_description":"Methods: The proliferative ability was analyzed by the WST-8 assay. Cell cycle was evaluated by flow cytometry after staining of cells with PI. Apoptosis was quantified by flow cytometry after double-staining of cells by Annexin-V/PI. Molecular changes of cell cycle and apoptosis were determined by Western blot. Intracellular calcium levels and mitochondrial membrane potentials were determined using Fluo-4/AM dye and JC-10 dye, respectively. Moreover, we examined the in vivo anti-MM effects of CaM antagonists using a murine xenograft model of the human MM cell line.","subitem_description_language":"en","subitem_description_type":"Abstract"},{"subitem_description":"Results: Treatment with W-7 and W-13 resulted in the dose-dependent inhibition of cell proliferation in various MM cell lines. W-7 and W-13 induced G1 phase cell cycle arrest by downregulating cyclins and upregulating p21cip1. In addition, W-7 and W-13 induced apoptosis via caspase activation; this occurred partly through the elevation of intracellular calcium levels and mitochondrial membrane potential depolarization and through inhibition of the STAT3 phosphorylation and subsequent downregulation of Mcl-1 protein. In tumor xenograft mouse models, tumor growth rates in CaM antagonist-treated groups were significantly reduced compared with those in the vehicle-treated groups.","subitem_description_language":"en","subitem_description_type":"Abstract"},{"subitem_description":"Conclusions: Our results demonstrate that CaM antagonists induce cell cycle arrest, induce apoptosis via caspase activation, and inhibit tumor growth in a murine MM model and raise the possibility that inhibition of CaM might be a useful therapeutic strategy for the treatment of MM.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第630号"}]},"item_10006_relation_15":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1186/1471-2407-14-882","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://dl.ndl.go.jp/pid/11337594","subitem_relation_type_select":"URI"}},{"subitem_relation_type":"hasVersion","subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4258255/","subitem_relation_type_select":"URI"}}]},"item_10006_relation_22":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"25424011","subitem_relation_type_select":"PMID"}}]},"item_10006_relation_28":{"attribute_name":"論文ID（NAID）","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"500001356623","subitem_relation_type_select":"NAID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright © 2014, Yokokura et al.; licensee BioMed Central Ltd.","subitem_rights_language":"en"},{"subitem_rights":"This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.","subitem_rights_language":"en","subitem_rights_resource":"http://creativecommons.org/licenses/by/4.0/"},{"subitem_rights":"The Creative Commons Public Domain Dedication waiver applies to the data made available in this article, unless otherwise stated.","subitem_rights_resource":"http://creativecommons.org/publicdomain/zero/1.0/"}]},"item_10006_text_30":{"attribute_name":"KEID","attribute_value_mlt":[{"subitem_text_value":"28748"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_fa2ee174bc00049f","subitem_version_type":"P"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Yokokura, Shigeyuki","creatorNameLang":"en"},{"creatorName":"横倉, 繁行","creatorNameLang":"ja"},{"creatorName":"ヨコクラ, シゲユキ","creatorNameLang":"ja-Kana"}],"familyNames":[{"familyName":"Yokokura","familyNameLang":"en"},{"familyName":"横倉","familyNameLang":"ja"},{"familyName":"ヨコクラ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"Shigeyuki","givenNameLang":"en"},{"givenName":"繁行","givenNameLang":"ja"},{"givenName":"シゲユキ","givenNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"267","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"9000387325945 ","nameIdentifierScheme":"CiNii ID","nameIdentifierURI":"http://ci.nii.ac.jp/nrid/9000387325945 "},{"nameIdentifier":"60769438","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=60769438"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-11-06"}],"displaytype":"detail","filename":"Med_A630.pdf","filesize":[{"value":"2.3 MB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://kagawa-u.repo.nii.ac.jp/record/384/files/Med_A630.pdf"},"version_id":"7827902b-5125-4bcc-9926-3a03d068c6aa"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-11-06"}],"displaytype":"detail","filename":"Med_A630_abstract.pdf","filesize":[{"value":"71.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"内容の要旨","objectType":"abstract","url":"https://kagawa-u.repo.nii.ac.jp/record/384/files/Med_A630_abstract.pdf"},"version_id":"a49d857c-cd27-4c5d-ba24-c5b839bceae4"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-11-06"}],"displaytype":"detail","filename":"Med_A630_result.pdf","filesize":[{"value":"758.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査の結果の要旨","objectType":"other","url":"https://kagawa-u.repo.nii.ac.jp/record/384/files/Med_A630_result.pdf"},"version_id":"dc340e2a-30ca-4b4b-852e-28c6fffcd31d"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Calmodulin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Multiple myeloma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cell cycle","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Apoptosis","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":"Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-07-17"},"publish_date":"2019-07-17","publish_status":"0","recid":"384","relation_version_is_last":true,"title":["Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2024-08-23T02:27:40.315084+00:00"}