{"created":"2024-10-28T02:53:15.093414+00:00","id":2004153,"links":{},"metadata":{"_buckets":{"deposit":"0610c067-42f2-4d55-a5f2-b91f13313dc2"},"_deposit":{"created_by":7,"id":"2004153","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2004153"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02004153","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["1555","1572","814","1431","349","296","677","1412","287","175"],"control_number":"2004153","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"大腸癌における抗EGFR抗体薬治療後のEGFR Downregulationは抗腫瘍効果を予測する","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"EGFR Down-regulation Predicts anti-EGFR Response","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-07-11","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"10","bibliographicPageEnd":"1454","bibliographicPageStart":"1445","bibliographicVolumeNumber":"15","bibliographic_titles":[{"bibliographic_title":"Molecular Cancer Research","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is reported to induce EGFR internalization in colorectal cancer (CRC) cells. However, the biological relevance of EGFR internalization with anti-EGFR mAb is unknown. Therefore, the relevance of EGFR downregulation with anti-EGFR mAb to anti-tumor activity in CRC cells was investigated. Quantification of EGFR on the cell surface before cetuximab treatment was assessed by flow cytometry, and its growth-inhibitory effects were measured by trypan blue-exclusion, in 10 RAS, BRAF wild-type CRC cell lines, but there was no significant correlation between EGFR number and its growth-inhibitory effect. However, a significant correlation existed between the percentage decrease in the number of EGFRs after cetuximab treatment and its growth-inhibitory effect in those cell lines. Treatment with TGF-α, a ligand for EGFR, induced EGFR internalization in CRC cells, but most EGFRs subsequently\nrecycled to the cell surface, consistent with previous studies. While cetuximab treatment induced EGFR internalization, most receptors subsequently translocated into the late endosome, leading to lysosomal degradation, as revealed by immunoblotting and double immunofluorescence. Cetuximab-sensitive CRC cells showed greater EGFR internalization, stronger cell growth inhibition, and more augmented apoptotic signals than non-sensitive cells. Immunohistochemistry (IHC) for EGFR, performed using an EGFR pharmDx™kit (mouse anti-human EGFR mAb clone 2-18C9), in clinical specimens before and after anti-EGFR mAb therapy in 13 CRC patients showed a significant correlation between the response to anti-EGFR mAb and decreased staining after therapy.\nImplications: This report clearly demonstrates that anti-EGFR mAb facilitates internalization and subsequent degradation of EGFRs in lysosomes, which is an important determinant of the efficacy of anti-EGFR mAb treatment for colorectal cancer.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Association for Cancer 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徳島大学大学院医科学教育部（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1351号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1158/1541-7786.MCR-16-0383"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1158/1541-7786.MCR-16-0383","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"332062"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"岡田, 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