{"created":"2024-12-18T04:20:09.041805+00:00","id":2001116,"links":{},"metadata":{"_buckets":{"deposit":"f0a0b467-9b7b-4183-968f-560923ecd80c"},"_deposit":{"created_by":15,"id":"2001116","owner":"15","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"2001116"},"status":"published"},"_oai":{"id":"oai:mie-u.repo.nii.ac.jp:02001116","sets":["334:608:618:1721969789237"]},"author_link":[],"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-09-25","bibliographicIssueDateType":"Issued"}}]},"item_7_date_granted_59":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-09-25"}]},"item_7_degree_grantor_57":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"三重大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"14101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_7_degree_name_56":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background/aim: Osteosarcoma (OS) is the most common malignant bone tumor. As the same agents have been in use since the mid-1970s, new therapeutic approaches are needed to improve prognosis. Pazopanib (PZP) has already demonstrated marked antitumor activity clinically and can be effective in patients with metastatic OS. We investigated the combination treatment of candidate agents with PZP and examined effects on tumor growth using an in vivo model.\nMaterials and methods: A library of 324 compounds was used. MG63 OS cells were treated with PZP and each compound. Cell viability was measured. The antiproliferative effects of compound combination on four OS cell lines was tested. Cell signaling was evaluated by western blot analysis. In vivo antitumor testing was performed using 143B-bearing mice.\nResults: The screening process identified crizotinib (CRZ) as the most effective drug for combination with PZP. The combination of PZP and CRZ demonstrated effects compared to control or single therapy. Cell signal investigation showed that dual therapy down-regulated c-MYC, p-AKT, p-STAT3, p-cyclin D1 and survivin and up-regulated cleaved caspase-3 and cleaved PARP compared to control or single therapy. In vivo analysis showed dual therapy achieved synergic effects for tumor growth compared to control or single-treatment groups. No significant difference in the change in body weight was observed among groups.\nConclusion: Combined use of PZP and CRZ offers synergic anti-tumor effects against OS, inducing apoptosis in vitro and in vivo by down-regulating AKT and STAT3. Our data suggest that these agents can be used for patients clinically.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_7_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"本文/Department of Orthopedic Surgery, Mie University School of Medicine, Tsu, Japan","subitem_description_type":"Other"},{"subitem_description":"8p","subitem_description_type":"Other"}]},"item_7_dissertation_number_60":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"乙医学第1103号"}]},"item_7_publisher_30":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"三重大学"}]},"item_7_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.21873/anticanres.16902","subitem_relation_type_select":"DOI"}}]},"item_7_text_31":{"attribute_name":"出版者（ヨミ）","attribute_value_mlt":[{"subitem_text_value":"ミエダイガク"}]},"item_7_text_63":{"attribute_name":"ノート","attribute_value_mlt":[{"subitem_text_value":"ANTICANCER RESEARCH 44: 1071-1078 (2024)に掲載"}]},"item_7_text_65":{"attribute_name":"資源タイプ（三重大）","attribute_value_mlt":[{"subitem_text_value":"Doctoral Dissertation / 博士論文"}]},"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":"矢田, 祐基","creatorNameLang":"ja"},{"creatorName":"ヤダ, ユウキ","creatorNameLang":"ja-Kana"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-18"}],"filename":"2024DM0920.pdf","filesize":[{"value":"421 KB"}],"format":"application/pdf","url":{"label":"2024DM0920.pdf","objectType":"fulltext","url":"https://mie-u.repo.nii.ac.jp/record/2001116/files/2024DM0920.pdf"},"version_id":"c27afb22-673b-4f1c-ace2-b27190dc3685"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Pazopanib","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"crizotinib","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"osteosarcoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"vascular endothelial growth factor receptor (VEGFR)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"platelet-derived growth factor receptor (PDGF)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"c-KIT","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"C-Met","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ALK","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ROS-1","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":"Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library","subitem_title_language":"en"}]},"item_type_id":"7","owner":"15","path":["1721969789237"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-12-18"},"publish_date":"2024-12-18","publish_status":"0","recid":"2001116","relation_version_is_last":true,"title":["Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library"],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2024-12-18T04:43:39.321519+00:00"}