{"created":"2023-07-27T06:58:40.068711+00:00","id":57553,"links":{},"metadata":{"_buckets":{"deposit":"878cfacf-cc75-4507-a53d-feb5483ea319"},"_deposit":{"created_by":18,"id":"57553","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57553"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057553","sets":["2812:2813:2832"]},"author_link":["97886","20160"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2003-09-16","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2000 – 2001","bibliographic_titles":[{"bibliographic_title":"平成13(2001)年度 科学研究費補助金 基盤研究(C) 研究概要"},{"bibliographic_title":"2001 Research Project Summary","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":"血管新生は胎児発生における血管系の発育に中心的役割を果たすだけでなく、生後では損傷の治癒、慢性低潅流領域における側副血行路の発達、さらに腫瘍の増殖などにも関与する生体応答であるこの生体応答を構成するのは血管内皮細胞であり、低酸素環境下における血管内皮細胞の増殖が血管新生の本態である。血流を必要とする細胞は、低酸素環境下において、VEGF(Vascular endothelial cell growth factor)をはじめとする増殖因子を産生、これに対し血管内皮細胞は増殖因子に対する受容体を発現、低潅流領域に選択的な血管新生が成立する。\n従来より、低酸素環境における血管新生に関しては、腫瘍細胞をはじめとする血流要求細胞がVEGFを誘導するメカニズムのみが研究され、低酸素環境での細胞内輸送に関する研究は全くなされていなかった。本研究では、血管新生のきわめて盛んなヒトglioblastoma病理組織で、血管周囲でのORP150の発現とVEGFの発現パターンがきわめてよく一致することを見いだした。このことは、血流の相対的不足部位で、これらの小胞体分子シャペロンが腫瘍細胞からのVEGF分泌に深く関わることを示唆している。さらにアデノウイルスベクターを用いてORP150による遺伝子治療を行うことにより、強力な血管新生因子であるVEGFが低酸素環境で産生されるためには、ORP150を介する経路が必須であることを示し、将来的にはORP150の発現調節による血管新生のコントロール、ガン増殖・進行の抑止が可能であることを示した。","subitem_description_type":"Abstract"},{"subitem_description":"Newly synthesized protein and immature proteins are easily aggregated because they ej(pose hydrophobic regions. Many stress conditions, such as heat shock or hypoxia, slow down their folding process and cause accumulation of unfolded/misfolded proteins in the cell. Molecular chaperones, including heat shock'proteins (IISPs), are induced in these conditions, bind to unfolded/misfolded proteins, and help them to be folded or reflolded properly. The protective role of molecular chaperones for the cells under stress has been reported.\nExpression of angiogenic factors such as vascular endothelial growth factor (VEGF) under conditions of cell stress involves both transcriptionaland translational events, as well as an important role for inducible endoplasmicreticulum (ER) chaperones. Coexpression of VEGF and 150-kDaoxygen-regulated protein (ORP), a novel ER chaperone, in human glioblastomasuggested a link between angiogenesis and ORP150. C6 gliomacells stably transfected with ORP150 antisense displayed selectively reduced ORP150 expression. Tumors raised after in culation of immunocompromisedmice with ORP150 antisense C6 glioma transfectants demonstratedan initial phase of growth comparable to wild-type C6 gliomacells which was followed by marked regression within 8 days. Decreaseddensity of platelet/endothelial cell adhesion molecule 1-positive structureswithin the tumor bed was consistent with reduced angiogenesis in C6 gliomas expressing ORP150 antisense, compared with tumors derived from C6 cells overexpressing ORP150 sense or vector controls. In vitro,inhibition of ORP150 expression decreased release of VEGF into culturesupernatants ; in ORP150 antisense transfectants, VEGF accumulatedintracellularly within the ER. These findings demonstrate a critical rolefor the inducible ER chaperone ORP150 in tumor-mediated angiogenesisvia processing of VEGF, and, thus, highlight a new facet of angiogenicmechanisms amenable to therapeutic manipulation in tumors.\nHeat shock proteins (HSPs)/stress proteins are molecular chaperflnes that are induced by various environmental and physiological stimuli. Evidence of the relations between the expression of HSPs and the regulation of cell growth or transformation has accumulated. The 150-kDa oxygen-regulated protein (ORP150), a new member of lisp family, functions as a molecular chaperone in the endoplasmic reticulum. We have examined whether transduced antisense ORP150 cDNA reduces tumorigenicity and angiogenicity. Relations between these stress proteins and cancer and possibilities for anticancer gene therapy are described.","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:12671522, 研究期間(年度):2000 – 2001","subitem_description_type":"Other"},{"subitem_description":"出典：「新規分子シャペロンORP150を利用した遺伝子治療に関する実験的研究」研究成果報告書　課題番号12671522\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（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12671522/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063823","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=90283746"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=90283746","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12671522/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12671522/","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":"2021-09-03"}],"displaytype":"detail","filename":"ME-PR-OGAWA-S-kaken 2003-2p.pdf","filesize":[{"value":"107.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-OGAWA-S-kaken 2003-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57553/files/ME-PR-OGAWA-S-kaken 2003-2p.pdf"},"version_id":"41e53c68-6af1-47a4-9cab-dd4b91d5a8c3"}]},"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":"新規分子シャペロンORP150を利用した遺伝子治療に関する実験的研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"新規分子シャペロンORP150を利用した遺伝子治療に関する実験的研究"},{"subitem_title":"Experimental research for the availability of gene therapy using ORP150, a novel molecular chaperone","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2832"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-09-03"},"publish_date":"2021-09-03","publish_status":"0","recid":"57553","relation_version_is_last":true,"title":["新規分子シャペロンORP150を利用した遺伝子治療に関する実験的研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:57:11.215160+00:00"}