{"created":"2023-05-15T09:47:28.384371+00:00","id":9562,"links":{},"metadata":{"_buckets":{"deposit":"2a78ef0c-3d5f-41f1-92ab-c5c073a7aa00"},"_deposit":{"created_by":11,"id":"9562","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"9562"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00009562","sets":["13:40"]},"author_link":["3494"],"item_10006_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"ソラフェニブ耐性肝細胞に対するレンバチニブの効果の評価","subitem_alternative_title_language":"ja"}]},"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2022-03-24"}]},"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":"Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.","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810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/10.3390/ijms222313071","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"hasVersion","subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8657692/","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":"34884875","subitem_relation_type_select":"PMID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2021 by the authors. Licensee MDPI, Basel, Switzerland.","subitem_rights_language":"en"},{"subitem_rights":"This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).","subitem_rights_language":"en"}]},"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":"石, 婷婷","creatorNameLang":"ja"},{"creatorName":"シ, ティエンティエン","creatorNameLang":"ja-Kana"},{"creatorName":"Shi, Tingting ","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-04-22"}],"displaytype":"detail","filename":"Med_A810.pdf","filesize":[{"value":"9.4 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/9562/files/Med_A810.pdf"},"version_id":"8ae8a41d-53d5-423f-8c66-59efcd138653"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-04-22"}],"displaytype":"detail","filename":"Med_A810_abstract.pdf","filesize":[{"value":"35.7 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/9562/files/Med_A810_abstract.pdf"},"version_id":"bbf76c4c-24c6-4656-9ee7-f45e3d2d5baa"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-04-22"}],"displaytype":"detail","filename":"Med_A810_result.pdf","filesize":[{"value":"85.6 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/9562/files/Med_A810_result.pdf"},"version_id":"54755cea-e5a5-4c61-a4d9-c6312e089186"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"lenvatinib","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"sorafenib-resistant","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"hepatocellular carcinoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"FGFR4","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"autophagy","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"microRNA","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":"Evaluating the effect of lenvatinib on sorafenib-resistant hepatocellular carcinoma cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Evaluating the effect of lenvatinib on sorafenib-resistant hepatocellular carcinoma cells","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-04-22"},"publish_date":"2022-04-22","publish_status":"0","recid":"9562","relation_version_is_last":true,"title":["Evaluating the effect of lenvatinib on sorafenib-resistant hepatocellular carcinoma cells"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-10-16T02:32:00.633923+00:00"}