{"_buckets": {"deposit": "3fe4245e-69bf-4222-8dc6-819d0999f3c9"}, "_deposit": {"id": "21395", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "21395"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00021395", "sets": []}, "author_link": ["109522"], "item_14_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2020-03-31", "bibliographicIssueDateType": "Issued"}}]}, "item_14_date_granted_8": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2020-03-31"}]}, "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。ARCHIVES OF TOXICOLOGY. 93(6):1713-1725 (2019); doi:10.1007/s00204-019-02440-7.", "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": "王　暁経. A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice （高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる）. 信州大学, 2020, 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1185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=000475702100018"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "31004178"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/31004178/", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1007/s00204-019-02440-7"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1007/s00204-019-02440-7", "subitem_relation_type_select": "DOI"}}]}, "item_14_rights_69": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "This is a post-peer-review, pre-copyedit version of an article published in Archives of Toxicology. The final authenticated version is available online at: https://doi.org/10.1007/s00204-019-02440-7 ."}]}, "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1185号"}]}, "item_14_text_76": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Steatohepatitis; NF-kappa B; p62; Sqstm1-NRF2 axis; Fibrogenesis; Oxidative stress"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "HEPATOCELLULAR-CARCINOMA; EARLY-STAGE; PROTEIN; ACTIVATION; DISEASE; CANCER; ALPHA; DISRUPTION; P62/SQSTM1; CIRRHOSIS"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Previous epidemiological studies have suggested a link between high-cholesterol intake and liver disease progression, including hepatocellular carcinoma (HCC). However, the precise mechanism of hepatotoxicity and hepatocarcinogenesis caused by excessive cholesterol consumption remains unclear. We aimed to investigate the impact of dietary cholesterol using hepatitis C virus core gene transgenic (HCVcpTg) mice, which spontaneously developed HCC with age. Male HCVcpTg mice were treated for 15months with either a control diet or an isocaloric diet containing 1.5% cholesterol, and liver phenotypes and tumor-associated signaling pathways were evaluated. The high-cholesterol diet-fed HCVcpTg mice exhibited a significantly higher incidence of liver tumors compared with the control diet mice (100% vs. 41%, P\u003c0.001). The diet induced steatohepatitis with pericellular fibrosis and evoked higher mRNA expression of pro-inflammatory and pro-fibrotic mediators along with enhanced hepatocyte proliferation and greater oxidative and endoplasmic reticulum stress in the liver. Moreover, long-term consumption of cholesterol-rich diet activated nuclear factor-kappa B (NF-kappa B) and p62/sequestosome 1 (Sqstm1)-nuclear factor erythroid 2 (NRF2) axis, enhanced fibrogenesis, and consequently accelerated hepatic tumorigenesis. In conclusion, these results demonstrate that a high-cholesterol diet facilitates liver tumorigenesis by inducing steatohepatitis, promoting hepatocyte division, and up-regulating cellular stress and pro-inflammatory NF-kappa B and detoxifying p62/Sqstm1-NRF2 signals. Therefore, high dietary cholesterol should be avoided in HCV-infected patients to prevent development of steatohepatitis, liver fibrosis, and HCC."}]}, "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": "王, 暁経", "creatorNameLang": "ja"}], "nameIdentifiers": [{"nameIdentifier": "109522", "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": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "16MH201D_yoshi.pdf", "filesize": [{"value": "114.2 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 114200.0, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21395/files/16MH201D_yoshi.pdf"}, "version_id": "f08d6595-3522-48ac-9be2-1fedc6f6e211"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "16MH201D_shinsa.pdf", "filesize": [{"value": "116.4 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 116400.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21395/files/16MH201D_shinsa.pdf"}, "version_id": "2ebbb447-a6e4-4453-ae75-5aaac89fc46c"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "16MH201D_ronbun.pdf", "filesize": [{"value": "2.4 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "This is a post-peer-review, pre-copyedit version of an article published in Archives of Toxicology. The final authenticated version is available online at: https://doi.org/10.1007/s00204-019-02440-7 .", "licensetype": "license_note", "mimetype": "application/pdf", "size": 2400000.0, "url": {"label": "博士論文の全文", "objectType": "fulltext", "url": "https://soar-ir.repo.nii.ac.jp/record/21395/files/16MH201D_ronbun.pdf"}, "version_id": "0874a0c0-1e41-436c-93a9-915e7a9f46c8"}]}, "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": "A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice （高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる）", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice （高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる）", "subitem_title_language": "en"}]}, "item_type_id": "14", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/00022152", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2020-06-15"}, "publish_date": "2020-06-15", "publish_status": "0", "recid": "21395", "relation": {}, "relation_version_is_last": true, "title": ["A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice （高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる）"], "weko_shared_id": -1}