{"created":"2023-05-15T14:50:48.626764+00:00","id":69455,"links":{},"metadata":{"_buckets":{"deposit":"b7729638-bcee-4537-bfac-17c82028db71"},"_deposit":{"created_by":1,"id":"69455","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"69455"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00069455","sets":["10:28"]},"author_link":["681623","681626","681622","681619","681621","681627","681624","681625","681620"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2008-09-13","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Epidermal growth factor receptor (EGFR) is overexpressed and/or mutated in various cancers resulting in abnormal activation of the signaling pathway, which has been implicated in the pathogenesis of the disease. There have been several PET/SPECT probes proposed for EGFR imaging such as positron- or single photon-labeled-tyrosin kinase inhibitors and -antibodies. As they are dependent on the molecular structure of EGFR and its abundance, we attempted to develop a more versatile PET/SPECT probe which can capture the activation of EGFR signaling pathway. We selected SH2 domain of Grb2 as a biding component of the probe: Grb2 is an adaptor protein of activated-EGFR and there have been no mutation reported in the binding site of EGFR with SH2 domain. For the effective transport into cells, TAT was fused to SH2 domain at the N termini, and flag peptide was fused at the C termini for in vitro molecular analysis. We conducted basic studies to evaluate the feasibility of the probe design.  \n We examined the cellular uptake and the binding to EGFR of our probe in EGFR-overexpressing A431 cells and EGFR-negative MDA-MB435 cells. When the probe was labeled with I-125 and incubated with cells, the amount taken up into cells was significantly higher in A431 cells (25.3+/-3.5%) than MDA-MB435 cells (21.4+/-1.9%). In immunofluorescence experiment, the protein was co-localized with EGFR near the cell membrane in A431 cells, while the protein was localized as dots in cytosol in MDA-MB435 cells suggesting non-specific cellular uptake. In addition, when serum-starved A431 cells were stimulated with EGF, the binding with EGFR was about two-fold increased. The half-life of the protein was 30 min after the uptake into cells. \n We concluded that SH2 domain of Grb2 has a potential to detect activated EGFR, though our construct needs further improvement in its stability and reduction of non-specific cellular uptake.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"World Molecular Imaging Congress","subitem_description_type":"Other"}]},"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":"Saito, Yuriko"}],"nameIdentifiers":[{"nameIdentifier":"681619","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Furukawa, Takako"}],"nameIdentifiers":[{"nameIdentifier":"681620","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Arano, Yasushi"}],"nameIdentifiers":[{"nameIdentifier":"681621","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujibayashi, Yasuhisa"}],"nameIdentifiers":[{"nameIdentifier":"681622","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Saga, Tsuneo"}],"nameIdentifiers":[{"nameIdentifier":"681623","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"齋藤 有里子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"681624","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"古川 高子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"681625","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"荒野 泰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"681626","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"佐賀 恒夫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"681627","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":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Basic studies for imaging activated form of EGFR","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Basic studies for imaging activated form of EGFR"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2008-09-18"},"publish_date":"2008-09-18","publish_status":"0","recid":"69455","relation_version_is_last":true,"title":["Basic studies for imaging activated form of EGFR"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:14:17.282884+00:00"}