WEKO3
アイテム
{"_buckets": {"deposit": "c0243c41-0e4e-46c7-9722-c7d2c8ec0e9c"}, "_deposit": {"created_by": 1, "id": "49284", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "49284"}, "status": "published"}, "_oai": {"id": "oai:repo.qst.go.jp:00049284", "sets": ["1"]}, "author_link": ["497344", "497335", "497334", "497332", "497337", "497338", "497341", "497333", "497339", "497342", "497343", "497340", "497336", "497346", "497345"], "item_8_biblio_info_7": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2017-11", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "42", "bibliographicPageEnd": "7562", "bibliographicPageStart": "7551", "bibliographicVolumeNumber": "23", "bibliographic_titles": [{"bibliographic_title": "World Journal of Gastroenterology"}]}]}, "item_8_description_5": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "AIM\nTo investigate the therapeutic effect of combined\nintegrin α6β4-targeted radioimmunotherapy (RIT) and\nPI3K/mTOR inhibitor BEZ235 in a pancreatic cancer\nmodel.\nMETHODS\nPhosphorylation of Akt, mTOR, the downstream\neffectors eukaryotic initiation factor 4E binding\nprotein 1 (4EBP1) and S6 ribosomal protein (S6) were\nevaluated in BxPC-3 human pancreatic cancer cells\ntreated with Yttrium-90 (90Y) labeled anti-integrin α6β4\nantibody (ITGA6B4) and BEZ235 by western blotting.\nThe cytotoxic effect of BEZ235 was investigated\nusing a colony formation assay. Therapeutic efficacy\nenhancement by oral BEZ235 administration was\nassessed using mice bearing BxPC-3 xenograft tumors.\nTumor volume measurements and immunohistochemical\nanalyses (cell proliferation marker Ki-67, DNA damage\nmarker p-H2AX and p-4EBP1 staining) of tumors were\nperformed for evaluation of combined treatment with\n90Y-ITGA6B4 plus BEZ235, or each arm alone.\nRESULTS\nWe found that phosphorylation of Akt (p-Akt), 4EBP1\n(p-4EBP1) and S6 (p-S6) was inhibited by BEZ235.\nColony formation in BxPC-3 cells was additively\nsuppressed by the combination of 90Y-ITGA6B4 and\nBEZ235. Pretreatment with BEZ235 before 90Y-ITGA6B4\nexposure resulted in significant reduction of cells plating\nefficiency (PE) (0.54 ± 0.11 vs 2.81 ± 0.14 with 185\nkBq/mL 90Y-ITGA6B4 exposure, P \u003c 0.01; 0.39 ± 0.08\nvs 1.88 ± 0.09 with 370 kBq/mL 90Y-ITGA6B4 exposure,\nP \u003c 0.01) when 5 × 103 cells per dish were plated. In\nvivo , the combined treatment with 90Y-ITGA6B4 plus\nBEZ235 enhanced the inhibition of tumor growth and\nstatistically significant differences of relative tumor\nvolume were observed for 27 d after the treatment\nstart date when compared with the 90Y-ITGA6B4 single\ninjection treatment (1.03 ± 0.38 vs 1.5 ± 0.15 at Day\n27, P \u003c 0.05), and for 41 d when compared with the\nBEZ235 treatment alone (1.8 ± 0.7 vs 3.14 ± 1.19\nat Day 41, P \u003c 0.05). Tumors from treatment groups\nshowed reduction in volumes, decreased Ki-67-positive\ncells, increased p-H2AX-positive cells and decreased\np-4EBP1 expression.\nCONCLUSION\nThe therapeutic efficacy of 90Y-ITGA6B4-RIT can be\nimproved by combining with dual PI3K and mTOR\ninhibitor, BEZ235, in a pancreatic cancer model\nsuggesting potential clinical application.\nKey words: Radioimmunotherapy; Pancreatic cancer;\nanti-integrin α6β4 antibody; Yttrium-90; NVP-BEZ235", "subitem_description_type": "Abstract"}]}, "item_8_publisher_8": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "Baishideng Publishing Group Inc"}]}, "item_8_relation_13": {"attribute_name": "PubMed番号", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "29204055", "subitem_relation_type_select": "PMID"}}]}, "item_8_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.3748/wjg.v23.i42.7551", "subitem_relation_type_select": "DOI"}}]}, "item_8_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1007-9327", "subitem_source_identifier_type": "ISSN"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Winn, Aung"}], "nameIdentifiers": [{"nameIdentifier": "497332", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tsuji, Atsushi"}], "nameIdentifiers": [{"nameIdentifier": "497333", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sudo, Hitomi"}], "nameIdentifiers": [{"nameIdentifier": "497334", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sugyo, Aya"}], "nameIdentifiers": [{"nameIdentifier": "497335", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ukai, Yoshinori"}], "nameIdentifiers": [{"nameIdentifier": "497336", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kouda, Katsushi"}], "nameIdentifiers": [{"nameIdentifier": "497337", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kurosawa, Yoshikazu"}], "nameIdentifiers": [{"nameIdentifier": "497338", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Furukawa, Takako"}], "nameIdentifiers": [{"nameIdentifier": "497339", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Saga, Tsuneo"}], "nameIdentifiers": [{"nameIdentifier": "497340", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Higashi, Tatsuya"}], "nameIdentifiers": [{"nameIdentifier": "497341", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "U Winn Aung", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "497342", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "辻 厚至", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "497343", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "須藤 仁美", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "497344", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "須尭 綾", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "497345", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "東 達也", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "497346", "nameIdentifierScheme": "WEKO"}]}]}, "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": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor"}]}, "item_type_id": "8", "owner": "1", "path": ["1"], "permalink_uri": "https://repo.qst.go.jp/records/49284", "pubdate": {"attribute_name": "公開日", "attribute_value": "2018-11-27"}, "publish_date": "2018-11-27", "publish_status": "0", "recid": "49284", "relation": {}, "relation_version_is_last": true, "title": ["Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor"], "weko_shared_id": -1}
Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor
https://repo.qst.go.jp/records/49284
https://repo.qst.go.jp/records/4928495cf8982-aac4-4201-bdd5-abd9ec46a4f7
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-11-27 | |||||
タイトル | ||||||
タイトル | Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Winn, Aung
× Winn, Aung× Tsuji, Atsushi× Sudo, Hitomi× Sugyo, Aya× Ukai, Yoshinori× Kouda, Katsushi× Kurosawa, Yoshikazu× Furukawa, Takako× Saga, Tsuneo× Higashi, Tatsuya× U Winn Aung× 辻 厚至× 須藤 仁美× 須尭 綾× 東 達也 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic cancer model. METHODS Phosphorylation of Akt, mTOR, the downstream effectors eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with Yttrium-90 (90Y) labeled anti-integrin α6β4 antibody (ITGA6B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing BxPC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses (cell proliferation marker Ki-67, DNA damage marker p-H2AX and p-4EBP1 staining) of tumors were performed for evaluation of combined treatment with 90Y-ITGA6B4 plus BEZ235, or each arm alone. RESULTS We found that phosphorylation of Akt (p-Akt), 4EBP1 (p-4EBP1) and S6 (p-S6) was inhibited by BEZ235. Colony formation in BxPC-3 cells was additively suppressed by the combination of 90Y-ITGA6B4 and BEZ235. Pretreatment with BEZ235 before 90Y-ITGA6B4 exposure resulted in significant reduction of cells plating efficiency (PE) (0.54 ± 0.11 vs 2.81 ± 0.14 with 185 kBq/mL 90Y-ITGA6B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 kBq/mL 90Y-ITGA6B4 exposure, P < 0.01) when 5 × 103 cells per dish were plated. In vivo , the combined treatment with 90Y-ITGA6B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the 90Y-ITGA6B4 single injection treatment (1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone (1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2AX-positive cells and decreased p-4EBP1 expression. CONCLUSION The therapeutic efficacy of 90Y-ITGA6B4-RIT can be improved by combining with dual PI3K and mTOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application. Key words: Radioimmunotherapy; Pancreatic cancer; anti-integrin α6β4 antibody; Yttrium-90; NVP-BEZ235 |
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書誌情報 |
World Journal of Gastroenterology 巻 23, 号 42, p. 7551-7562, 発行日 2017-11 |
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出版者 | ||||||
出版者 | Baishideng Publishing Group Inc | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1007-9327 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 29204055 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3748/wjg.v23.i42.7551 |