{"created":"2023-07-27T06:50:06.504585+00:00","id":42589,"links":{},"metadata":{"_buckets":{"deposit":"9f4938c3-3671-418a-a7f7-bc898b5ea0b5"},"_deposit":{"created_by":18,"id":"42589","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"42589"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00042589","sets":["2812:2813:2841"]},"author_link":["67981","67982"],"item_10007_biblio_info_24":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicPageStart":"7p.","bibliographicVolumeNumber":"1991-1992","bibliographic_titles":[{"bibliographic_title":"平成4(1992)年度 科学研究費補助金 一般研究(B) 研究成果報告書"},{"bibliographic_title":"1992 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_10007_date_8":{"attribute_name":"報告年度","attribute_value_mlt":[{"subitem_date_issued_datetime":"1993-03","subitem_date_issued_type":"Issued"}]},"item_10007_description_13":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"P糖蛋白が脳内毛細血管内皮細胞及び脳腫瘍の細胞膜透過性に及ぼす影響について、薬物動態学的、生化学的及び免疫組織化学的な検索を行った、ラットの脳に15万個の9Lグリオーマ細胞を定位脳的に移植した後2週間目に,1)ラジオアイソトープでラベルした薬剤を頚動脈内に注入し,5秒間での脳内及び腫瘍内への移行を液体シンチレーションカウンターにより測定し,Oldendorfらの方法により解析した.さらに,2)薬剤を細胞外に排出することで癌細胞の多剤薬剤耐性に関与するP-糖蛋白の有無を,C-219モノクローナル抗体を用いて脳内毛細血管,腫瘍内血管及び腫瘍細胞膜において免疫組織化学的に検索し,3)これらの超微構造との関連を検索した.その結果,1)血液-脳関門を移行しないはずのシュクロースは9Lグリオーマ内に脳内への取り込みの5倍移行した.MCNUと5-FU,アドリアマイシンはシュクロースと同様に正常脳内へはほとんど移行しなかったが,ACNUはシュクロースよりは有意に多く移行した.MCNUとアドリアマイシンはコントロールであるシュクロースと同様,腫瘍内には十分に取り込まれたが,腫瘍細胞内へは取り込まれなかった。一方,ACNUと5-FUは腫瘍細胞内にも著明に取り込まれた.5-FUの培養9Lグリオーマ細胞内への移行は,ATP阻害剤や4℃の培養液中で著しく減少した.2)脳内毛細血管の内皮細胞と9Lグリオーマの腫瘍細胞膜では免疫組織化学的にP-糖蛋白の発現がみられたが,腫瘍内血管の内皮細胞にはみられなかった.3)腫瘍内血管の内皮細胞には電顕的に多数の窓形成や内皮細胞の腫大,及び内皮細胞間隙の開大等が観察された.以上より,MCNUや5-FU,アドリアマイシンの脳内への移行のみならず,MCNUやアドリアマイシンの9Lグリオーマ細胞内への移行は,それぞれ脳内毛細血管内皮細胞膜と腫瘍細胞膜に発現したP-糖蛋白による細胞外排出の為制限されているものと推定された.","subitem_description_type":"Abstract"},{"subitem_description":"Two weeks after the inoculation of 1.5x10^5 of 9L glioma cells into the rat brain, the transfer of radiolabelled drugs into the brain and the experimental 9L glioma during the first cerebral circulation,was measured with a liquid scintilation counter and analyzed by the method of Oldendorf. The expression of P-glycoprotein, which is known to be associated with the efflux of drugs, was also studied, using anti-P-glycoprotein monoclonal antibody: C-219. Furthermore, the ultrastructure of brain capillaries, tumor vessels and glioma cells was studied by conventional and immuno-electron microscopy. Sucrose (control), the transport of which through the blood-brain barrier is known to be saturable, accumulated to 5 fold higher levels in the tumor relative to brain. MCNU (ranimustine: methyl 6-[3-(2-chloroethyl-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside), 5-FU (5-fluorouracil) and doxorubicin (Adriamycin) showed quite little accumulation into the normal brain, whereas ACNU (nimustine: 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride) showed an increased accumulation. MCNU and doxorubicin showed negligible accumulation in the glioma cells despite diffusion into the tumor interstitial space. In contrast, ACNU and 5-FU showed an increased accumulation in tumor cells. The transfer of 5-FU into the cultured 9L glioma cells was decreased by ATP inhibitors or by low temperature. Although both brain capillary endothelial cells and glioma cell membranes were immunohistochemically positive for P-glycoprotein, the tumor vasculature showed low expression of P-glycoprotein. The endothelial cells of tumor vessels ultrastructurally showed increased fenestrations, swelling and disrupted junctions. Accordingly, it is suggested that hydrophilic drugs such as doxorubicin, being pumped out by P-glycoprotein, do not accumulate in 9L glioma as do other lipophilic drugs such as ACNU, or 5-FU associated with the carrier-mediated mechanism.","subitem_description_type":"Abstract"}]},"item_10007_description_14":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:03454347, 研究期間(年度):1991-1992","subitem_description_type":"Other"},{"subitem_description":"研究機関: 金沢大学医学部","subitem_description_type":"Other"},{"subitem_description":"出典：「P糖蛋白の血液ー脳関門及び脳腫瘍の細胞膜透過性に対する効果」研究成果報告書　課題番号03454347\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_10007_description_4":{"attribute_name":"研究代表者ID","attribute_value_mlt":[{"subitem_description":"60135077","subitem_description_type":"Other"}]},"item_10007_description_9":{"attribute_name":"研究課題番号","attribute_value_mlt":[{"subitem_description":"03454347","subitem_description_type":"Other"}]},"item_10007_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00048944","subitem_identifier_reg_type":"JaLC"}]},"item_10007_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=60135077"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=60135077","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03454347/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03454347/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-03454347/034543471992kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-03454347/034543471992kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_10007_version_type_20":{"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":"2017-11-16"}],"displaytype":"detail","filename":"ME-PR-YAMASHIMA-T-kaken 1993-7p.pdf","filesize":[{"value":"293.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-YAMASHIMA-T-kaken 1993-7p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/42589/files/ME-PR-YAMASHIMA-T-kaken 1993-7p.pdf"},"version_id":"9c2d5934-45f0-411c-a3a5-2d7126e162c3"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"薬剤移行","subitem_subject_scheme":"Other"},{"subitem_subject":"脳内毛細血管","subitem_subject_scheme":"Other"},{"subitem_subject":"腫瘍細胞膜","subitem_subject_scheme":"Other"},{"subitem_subject":"9Lグリオーマ","subitem_subject_scheme":"Other"},{"subitem_subject":"P-糖蛋白","subitem_subject_scheme":"Other"},{"subitem_subject":"drug transfer","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"brain capillary endothel","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"tumor cell membrane","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"9L glioma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"P-glycoprotein","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_researcher":{"attribute_name":"研究代表者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山嶋, 哲盛"}],"nameIdentifiers":[{"nameIdentifier":"67981","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"60135077","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=60135077"}]},{"creatorNames":[{"creatorName":"Yamashima, Tetsumori"}],"nameIdentifiers":[{"nameIdentifier":"67982","nameIdentifierScheme":"WEKO"}]}]},"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":"P糖蛋白の血液ー脳関門及び脳腫瘍の細胞膜透過性に対する効果","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"P糖蛋白の血液ー脳関門及び脳腫瘍の細胞膜透過性に対する効果"},{"subitem_title":"Drug transfer and expression of p-glycoprotein in the rat 9L glioma","subitem_title_language":"en"}]},"item_type_id":"10007","owner":"18","path":["2841"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-11-16"},"publish_date":"2017-11-16","publish_status":"0","recid":"42589","relation_version_is_last":true,"title":["P糖蛋白の血液ー脳関門及び脳腫瘍の細胞膜透過性に対する効果"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:52:39.269554+00:00"}