{"created":"2023-06-19T08:45:17.766928+00:00","id":500,"links":{},"metadata":{"_buckets":{"deposit":"676ad33c-b3fa-4f27-891a-feb6e99277a2"},"_deposit":{"created_by":25,"id":"500","owners":[25],"pid":{"revision_id":0,"type":"depid","value":"500"},"status":"published"},"_oai":{"id":"oai:ycu.repo.nii.ac.jp:00000500","sets":["4:71:228:229"]},"author_link":["678","677"],"item_10002_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-01-31","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"61","bibliographicPageStart":"59","bibliographicVolumeNumber":"67","bibliographic_titles":[{"bibliographic_title":"横浜医学"},{"bibliographic_title":"Yokohama Medical Journal","bibliographic_titleLang":"en"}]}]},"item_10002_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"免疫応答に関わる転写因子であるNFATc 1 が正常組織に比べ各種癌組織で発現が上昇しているとの報告が散見される．また諸説あるものの，疫学調査において腎不全による人工透析患者に比べ腎移植後に免疫抑制剤を服用していた患者の方が膀胱癌発生率が低下したと報告されている．しかしながら，そのメカニズムについては不明であった．NFATc 1 は免疫抑制剤の主要標的であることから，免疫抑制剤による膀胱癌罹患率の減少に強く関わっていると推測される．本研究では，免疫抑制剤がNFATc 1 を介して膀胱癌の発生・進展に抑制効果があるのかを検討した．\n膀胱癌組織アレイを用いNFATc 1 の発現を免疫組織学的染色により検討したところ，正常尿路上皮組織に比べ表在性膀胱腫瘍組織では有意にNFATc 1 の発現が高かった（p<0.05）．また，膀胱癌全摘後の再発率はNFATc 1 発現群で有意に高かった（p<0.01）．膀胱癌細胞株において，免疫抑制剤を刺激したところ，NFATc 1 発現・活性が有意に低下した．また，免疫抑制剤の刺激により細胞増殖能（生存度の減少およびアポトーシスの増加）・創傷癒合能・細胞浸潤能の低下やMMP- 2 ・MMP- 9 の発現・活性の低下を認めた．しかし，免疫抑制剤の効果は，NFATc 1 -shRNAを強制発現させた細胞株では認められなかった．正常尿路上皮細胞株であるSVHUCに発癌物質であるmethylcholanthrene （MCA）を暴露させたのちに免疫抑制剤を6週間刺激し続けた腫瘍発癌モデルで検討した．腫瘍化は，軟寒天を用いた足場形成能の獲得およびNOD-SCIDマウスにおける腫瘍定着率で評価した．膀胱癌発癌モデルでは，免疫抑制剤は足場形成能を有意に低下させた（p<0.01）．マウスにおいても，腫瘍定着率はコントロール群に比べて有意に低下した（p<0.01).\nNFATc 1 の発現は，表剤性膀胱腫瘍で正常尿路上皮より有意に高く，浸潤癌の予後とも相関したことから，新規分子マーカーとなりうると考えられた．また免疫抑制剤はNFATc 1 を介して膀胱癌の発生・進展を抑制したことから，新規治療法の可能性が示唆された．","subitem_description_type":"Abstract"}]},"item_10002_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"横浜市立大学医学会"}]},"item_10002_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0372-7726","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"河原, 崇司"},{"creatorName":"カワハラ, タカシ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kawahara, Takashi","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":"2016-06-01"}],"displaytype":"detail","filename":"10_Kawahara.pdf","filesize":[{"value":"745.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"横浜医学67巻1号（河原崇司）","url":"https://ycu.repo.nii.ac.jp/record/500/files/10_Kawahara.pdf"},"version_id":"4c56efc8-49b2-4ea2-8a0c-c09ecca62aea"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"免疫抑制剤","subitem_subject_scheme":"Other"},{"subitem_subject":"シクロスポリン","subitem_subject_scheme":"Other"},{"subitem_subject":"タクロリムス","subitem_subject_scheme":"Other"},{"subitem_subject":"NFATc₁","subitem_subject_scheme":"Other"},{"subitem_subject":"膀胱癌","subitem_subject_scheme":"Other"},{"subitem_subject":"immune-suppressive agent","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cyclosporine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"tacrolimus","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"NFATc₁","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"bladder cancer","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"免疫抑制剤を用いた膀胱癌の発生・進展抑制のメカニズム解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"免疫抑制剤を用いた膀胱癌の発生・進展抑制のメカニズム解明"},{"subitem_title":"NNUCLEAR FACTOR OF ACTIVATED T CELLS (NFAT) INDUCES BLADDER CANCER CELL PROLIFERATION","subitem_title_language":"en"}]},"item_type_id":"10002","owner":"25","path":["229"],"pubdate":{"attribute_name":"公開日","attribute_value":"2016-06-01"},"publish_date":"2016-06-01","publish_status":"0","recid":"500","relation_version_is_last":true,"title":["免疫抑制剤を用いた膀胱癌の発生・進展抑制のメカニズム解明"],"weko_creator_id":"25","weko_shared_id":25},"updated":"2023-06-19T10:03:43.015922+00:00"}