{"_buckets": {"deposit": "60c7e3a9-8647-4cd1-984c-7c343a14899e"}, "_deposit": {"id": "19972", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "19972"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00019972", "sets": []}, "author_link": ["105925"], "item_14_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2018-03-31", "bibliographicIssueDateType": "Issued"}}]}, "item_14_date_granted_8": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2018-03-31"}]}, "item_14_degree_grantor_10": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "信州大学(Shinshu university)"}], "subitem_degreegrantor_identifier": [{"subitem_degreegrantor_identifier_name": "13601", "subitem_degreegrantor_identifier_scheme": "kakenhi"}]}]}, "item_14_degree_name_9": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（医学）"}]}, "item_14_description_26": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "雑誌に発表。ONCOLOGY REPORTS. 39(2):843-850 (2018); doi:10.3892/or.2017.6153.", "subitem_description_type": "Other"}]}, "item_14_description_37": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Thesis", "subitem_description_type": "Other"}]}, "item_14_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "横井　謙太. Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib（胆管癌におけるソラフェニブによるRAF/MEK/ERK抑制機序からのAKT/mTOR シグナル伝達を介した細胞死回避機序）. 信州大学, 2018, 博士論文.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601甲第1128号"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000422855800046"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.3892/or.2017.6153"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.3892/or.2017.6153", "subitem_relation_type_select": "DOI"}}]}, "item_14_select_71": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "学位の区分", "attribute_value_mlt": [{"subitem_text_value": "doctoral"}]}, "item_14_text_12": {"attribute_name": "学位の分野", "attribute_value_mlt": [{"subitem_text_value": "医学"}]}, "item_14_text_13": {"attribute_name": "学位の報告番号", "attribute_value_mlt": [{"subitem_text_value": "甲第1128号"}]}, "item_14_text_76": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "sorafenib; cholangiocarcinoma; AKT Ser473; mTORC2 disassembly; everolimus"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "HEPATOCELLULAR-CARCINOMA; MAMMALIAN TARGET; UP-REGULATION; MTOR; CELLS; AKT; CANCER; SUPPRESSION; APOPTOSIS; AUTOPHAGY"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses. Sorafenib inhibited cell growth significantly less in CCC cells than in HCC cells, with lower suppression of ERK phosphorylation. Significantly decreased AKT Ser473 phosphorylation in HCC cells, and conversely enhanced phosphorylation of AKT Ser473 and mTORC2 in CCC cells, were observed with sorafenib treatment. Disassembly of the mTORC2 complex in RBE cells with siRNA targeting Rictor resulted in the downregulation of AKT Ser473 phosphorylation and enhanced apoptosis presumably via increased FOXO1, which consequently suppressed RBE cell proliferation. Phosphorylation of mTORC1 and autophagy were not influenced by sorafenib in CCC cells. Simultaneous administration of everolimus to suppress activated mTORC1 in RBE cells revealed that combined everolimus and sorafenib treatment under mTORC2 disassembly could enhance growth inhibition through the suppression of both sorafenib- and everolimus-dependent AKT Ser473 phosphorylation in addition to the inhibition of mTORC1 phosphorylation. Prevention of escape by AKT/mTOR signaling from the RAF/MEK/ERK pathway in sorafenib treatment by suppressing mTORC2 activity may lead to promising new approaches in CCC therapy."}]}, "item_1627890986942": {"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_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": "横井, 謙太", "creatorNameLang": "ja"}], "nameIdentifiers": [{"nameIdentifier": "105925", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-06-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "13MH046A_yoshi.pdf", "filesize": [{"value": "92.1 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 92100.0, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/19972/files/13MH046A_yoshi.pdf"}, "version_id": "98b18a94-9ac5-4fff-935f-354636411d37"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-06-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "13MH046A_shinsa.pdf", "filesize": [{"value": "97.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 97000.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/19972/files/13MH046A_shinsa.pdf"}, "version_id": "afa62f7c-2389-478e-8afd-2c19335399ff"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-06-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "13MH046A_ronbun.pdf", "filesize": [{"value": "606.2 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 606200.0, "url": {"label": "博士論文の全文", "objectType": "fulltext", "url": "https://soar-ir.repo.nii.ac.jp/record/19972/files/13MH046A_ronbun.pdf"}, "version_id": "301f3361-85b3-4669-bcf1-1a44239af388"}]}, "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": "Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib（胆管癌におけるソラフェニブによるRAF/MEK/ERK抑制機序からのAKT/mTOR シグナル伝達を介した細胞死回避機序）", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib（胆管癌におけるソラフェニブによるRAF/MEK/ERK抑制機序からのAKT/mTOR シグナル伝達を介した細胞死回避機序）", "subitem_title_language": "en"}]}, "item_type_id": "14", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/00020733", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2018-06-28"}, "publish_date": "2018-06-28", "publish_status": "0", "recid": "19972", "relation": {}, "relation_version_is_last": true, "title": ["Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib（胆管癌におけるソラフェニブによるRAF/MEK/ERK抑制機序からのAKT/mTOR シグナル伝達を介した細胞死回避機序）"], "weko_shared_id": -1}