{"created":"2023-05-15T14:59:53.920472+00:00","id":81281,"links":{},"metadata":{"_buckets":{"deposit":"12d6126c-1460-4743-80e1-e1c831f80b04"},"_deposit":{"created_by":1,"id":"81281","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"81281"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00081281","sets":["1"]},"author_link":["1005803","1005808","1005807","1005809","1005806","1005810","1005801","1005800","1005805","1005802","1005804"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageStart":"3652","bibliographicVolumeNumber":"12","bibliographic_titles":[{"bibliographic_title":"Cancers"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In treatment-refractory cancers, tumor tissues damaged by therapy initiate the repair response; therefore, tumor tissues must be exposed to an additional burden before successful repair. We hypothesized that an agent recognizing a molecule that responds to anticancer treatment-induced tissue injury could deliver an additional antitumor agent including a radionuclide to damaged cancer tissues during repair. We selected the extracellular matrix glycoprotein tenascin-C (TNC) as such a molecule, and three antibodies recognizing human and murine TNC were employed to evaluate X-irradiation-induced changes in TNC uptake by subcutaneous tumors. TNC expression was assessed by immunohistochemical staining of BxPC-3 tumors treated with or without X-irradiation (30 Gy) for 7 days. Antibodies against TNC (3-6, 12-2-7, TDEAR) and a control antibody were radiolabeled with In and injected into nude mice having BxPC-3 tumors 7 days after X-irradiation, and temporal uptake was monitored for an additional 4 days by biodistribution and single-photon emission computed tomography with computed tomography (SPECT/CT) studies. Intratumoral distribution was analyzed by autoradiography. The immunohistochemical signal for TNC expression was faint in nontreated tumors but increased and expanded with time until day 7 after X-irradiation. Biodistribution studies revealed increased tumor uptake of all three In-labeled antibodies and the control antibody. However, a statistically significant increase in uptake was evident only for In-labeled 3-6 (35% injected dose (ID)/g for 30 Gy vs. 15% ID/g for 0 Gy at day 1,  < 0.01), whereas limited changes in In-labeled TDEAR2, 12-2-27, and control antibody were observed (several % ID/g for 0 and 30 Gy). Serial SPECT/CT imaging with In-labeled 3-6 or control antibody provided consistent results. Autoradiography revealed noticeably stronger signals in irradiated tumors injected with In-labeled 3-6 compared with each of the nonirradiated tumors and the control antibody. The signals were observed in TNC-expressing stroma. Markedly increased uptake of In-labeled 3-6 in irradiated tumors supports our concept that an agent, such as an antibody, that recognizes a molecule involved in tissue injury repair, such as TNC, could enhance drug delivery to tumor tissues that have undergone therapy. The combination of antibody 3-6 coupled to a tumoricidal drug and conventional therapy has the potential to achieve better outcomes for patients with refractory cancer.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"33291427","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.3390/cancers12123652","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.mdpi.com/2072-6694/12/12/3652","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2072-6694","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":"Sugyo, Aya"}],"nameIdentifiers":[{"nameIdentifier":"1005800","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"B Tsuji, Atsushi"}],"nameIdentifiers":[{"nameIdentifier":"1005801","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sudo, Hitomi"}],"nameIdentifiers":[{"nameIdentifier":"1005802","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takano, Kanako"}],"nameIdentifiers":[{"nameIdentifier":"1005803","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kusakabe, Moriaki"}],"nameIdentifiers":[{"nameIdentifier":"1005804","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higashi, Tatsuya"}],"nameIdentifiers":[{"nameIdentifier":"1005805","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aya, Sugyo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1005806","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Atsushi, Tsuji","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1005807","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hitomi, Sudo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1005808","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kanako, Takano","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1005809","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Higashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1005810","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":"Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-12-11"},"publish_date":"2020-12-11","publish_status":"0","recid":"81281","relation_version_is_last":true,"title":["Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:22:25.241151+00:00"}