{"created":"2023-07-27T06:55:04.087079+00:00","id":50728,"links":{},"metadata":{"_buckets":{"deposit":"d6d4d0f0-6817-4b9e-801c-aefdaf70daf6"},"_deposit":{"created_by":18,"id":"50728","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50728"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050728","sets":["2812:2813:2829"]},"author_link":["91854","108"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"8p.","bibliographicVolumeNumber":"2003-2004","bibliographic_titles":[{"bibliographic_title":"平成16(2004)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2004 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"慢性肝炎から肝がんへ進展するB型肝炎ウイルス表面抗原のトランスジェニックマウスモデルを用いて、肝発がんの病態機序を解析するとともに、発がんを制御する分子のスクリーニングを進めた。検討結果は、以下のごとくである。\n1)肝発がんの病態の検討として、肝炎の誘導の際に行う各種の細胞免疫学的操作によって、前がん状態の異形性が変化し発がん率に違いが生ずることが分かった。異なるリンパ球分画によって誘導した慢性肝炎を観察したところ、CD8+Tリンパ球、CD4+Tリンパ球、B(CD19+)リンパ球の順に肝組織の異形性の程度、発がん率(それぞれ、86%、24%、0%)に寄与していることが明らかになった(Cancer Res.64:3326,2004)。\n2)これまで肝細胞障害に重要なFasリガンド(FasL)を介する経路を抑制すると、肝炎が軽快し発がんが著明に減少するという結果を得ているので(J.Exp.Med.196:1105,2002)、FasL抗体の投与による影響を約2万個の遺伝子解析が可能であるDNAチップを用いて検討した。抗体の投与によって352遺伝子(1.7%)の発現が有意に変動していた(P<0.05)。このうち機能が予測される遺伝子が190個認められた。なかでも、細胞死・増殖因子に関する遺伝子群の変動が4.7%と最も高率であった。\n3)発がんに関連する候補遺伝子の1例として、セリン・スレオニンキナーゼpim-3の解析を行うことによって、細胞増殖を促進しアポトーシス(細胞死)を抑制して肝がんの進展に関与していることが示唆された(Int.J.Cancer 114:209,2005)。\nこれらの結果から、発がん病態の細胞免疫学的特徴が明らかになるとともに、発がん過程に関与する遺伝子のスクリーニングを継続することによって肝発がんの制御に有用な遺伝子が絞り込まれる可能性が示された。","subitem_description_type":"Abstract"},{"subitem_description":"Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. Recently, we have reported that Fas ligand (FasL) is critically involved in the induction of chronic immune-mediated liver cell injury that increases HCC incidence (J Exp Med 196 : 1105, 2002) ; however, the molecular mechanisms potentially responsible for carcinogenesis are not well defined. In the current study, we asked the regulatory molecules in liver diseases that displayed different procarcinogenic potentials in a hpatitis B virus (HBV) transgenic mouse model. The results are summarized as follows.\n1)Transfer of CD8^+-enriched splenocytes caused prolonged disease kinetics and a marked increase in the extent of hepatocyte apoptosis and regeneration. In 12 out of 14 mice the transfer resulted in multiple hepatocellular carcinomas (HCCs) comparable to the manifestations seen in the mice transferred with total splenocytes. In contrast, mice that had received CD4^+-enriched cells demonstrated lower lev els of liver disease and developed fewer incidences of HCC (4 of 17). The experiment also revealed that all the groups of mice complicated with HCC developed comparable mean numbers and sizes of tumors. B cell depletion had no effect on disease kinetics in this model. (Cancer Res. 64 : 3326, 2004)\n2)During more than twelve months of disease progression, 352 (1.7 % of all) genes were expressed differentially between the mice treated with anti-FasL Ab and with PBS (P<0.05), 190 genes of which were assigned to functional groups based on Gene Ontology categories. In the gene groups of enzymes, cell communication, cellular components, signal transduction, and nucleic acid binding, the significant changes due to anti-FasL Ab treatment were observed in 43(1.6% of the gene group), 42(2.0%), 31(1.3%), 28(1.4%), and 22(1.8%) genes, respectively. In the cell communication group, high proportion (4.3%) of cell death control genes was involved in this expression dynamics.\n3)We identified several genes expressed differentially at the pre-malignant lesions. Among these genes, we focused on Pim-3, which is reported as a member of a proto-oncogene Pim family, but its contribution to hepatocarcinogenesis remains elusive. The mRNA expression was selectively detected in human hepatoma cell lines, but not in normal liver tissues. Pim-3 protein was also expressed in human hepatocellular carcinoma tissues and cell lines but not in normal hepatocytes. Moreover, cell proliferation was attenuated in human hepatoma cell lines, HepsB and HuH7, by RNA interference ablation of Pim-3 gene expression. (Int.J.Cancer 114 : 209, 2005)\nTaken together, these data suggest the molecular mechanisms potentially responsible for hepatocarcinogenesis and the future studies for the development of molecular targets.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:15590631, 研究期間(年度):2003-2004","subitem_description_type":"Other"},{"subitem_description":"出典：「トランスジェニックマウスモデルを用いた肝発がん制御分子の研究」研究成果報告書　課題番号15590631\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057036","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学附属病院"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=40293352"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=40293352","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15590631/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15590631/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15590631/155906312004kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15590631/155906312004kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-14"}],"displaytype":"detail","filename":"HO-PR-NAKAMOTO-Y-kaken 2005-8p.pdf","filesize":[{"value":"264.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-NAKAMOTO-Y-kaken 2005-8p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50728/files/HO-PR-NAKAMOTO-Y-kaken 2005-8p.pdf"},"version_id":"b79de6aa-75f3-4a64-9b51-acd3e607b7ea"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"トランスジェニックマウスモデルを用いた肝発がん制御分子の研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"トランスジェニックマウスモデルを用いた肝発がん制御分子の研究"},{"subitem_title":"A study of regulatory molecules involved in hepatocarcinogenesis in a transgenic mouse model","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2829"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-02-14"},"publish_date":"2020-02-14","publish_status":"0","recid":"50728","relation_version_is_last":true,"title":["トランスジェニックマウスモデルを用いた肝発がん制御分子の研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:28:44.821882+00:00"}