Extra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma

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dc.contributor.authorSaw, Phei Erko
dc.contributor.authorXu, Xiaodingko
dc.contributor.authorKang, Bo Ramko
dc.contributor.authorLee, Jungsulko
dc.contributor.authorLee, Yeo Songko
dc.contributor.authorKim, Chungyeulko
dc.contributor.authorKim, Hyungsinko
dc.contributor.authorKang, Shin-Hyukko
dc.contributor.authorNa, Yoo Jinko
dc.contributor.authorMoon, Hong Jooko
dc.contributor.authorKim, Joo Hanko
dc.contributor.authorPark, Youn-Kwanko
dc.contributor.authorYoon, Wonkiko
dc.contributor.authorKim, Jong Hyunko
dc.contributor.authorKwon, Taek-Hyunko
dc.contributor.authorChoi, Chulheeko
dc.contributor.authorJon, Sangyongko
dc.contributor.authorChong, Kyuhako
dc.date.accessioned2020-12-16T08:30:07Z-
dc.date.available2020-12-16T08:30:07Z-
dc.date.created2020-11-23-
dc.date.created2020-11-23-
dc.date.created2020-11-23-
dc.date.created2020-11-23-
dc.date.issued2021-01-
dc.identifier.citationTHERANOSTICS, v.11, no.2, pp.941 - 957-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10203/278572-
dc.description.abstractExtra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (similar to 12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo. Results: Brain tumors had a 1.42-fold cancer-to-normal ratio (p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group (p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APT(EDB)-DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.-
dc.languageEnglish-
dc.publisherIVYSPRING INT PUBL-
dc.titleExtra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma-
dc.typeArticle-
dc.identifier.wosid000585989200028-
dc.identifier.scopusid2-s2.0-85096306369-
dc.type.rimsART-
dc.citation.volume11-
dc.citation.issue2-
dc.citation.beginningpage941-
dc.citation.endingpage957-
dc.citation.publicationnameTHERANOSTICS-
dc.identifier.doi10.7150/thno.44948-
dc.contributor.localauthorChoi, Chulhee-
dc.contributor.localauthorJon, Sangyong-
dc.contributor.nonIdAuthorSaw, Phei Er-
dc.contributor.nonIdAuthorXu, Xiaoding-
dc.contributor.nonIdAuthorKang, Bo Ram-
dc.contributor.nonIdAuthorLee, Jungsul-
dc.contributor.nonIdAuthorLee, Yeo Song-
dc.contributor.nonIdAuthorKim, Chungyeul-
dc.contributor.nonIdAuthorKim, Hyungsin-
dc.contributor.nonIdAuthorKang, Shin-Hyuk-
dc.contributor.nonIdAuthorNa, Yoo Jin-
dc.contributor.nonIdAuthorMoon, Hong Joo-
dc.contributor.nonIdAuthorKim, Joo Han-
dc.contributor.nonIdAuthorPark, Youn-Kwan-
dc.contributor.nonIdAuthorYoon, Wonki-
dc.contributor.nonIdAuthorKim, Jong Hyun-
dc.contributor.nonIdAuthorKwon, Taek-Hyun-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorEDB-Fibronectin-
dc.subject.keywordAuthorGlioma-
dc.subject.keywordAuthorBig Data-
dc.subject.keywordAuthorBiomarkers-
dc.subject.keywordAuthorMicelles-
dc.subject.keywordPlusPOLYMERIC MICELLES-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusGLIOBLASTOMA-
dc.subject.keywordPlusRADIOIMMUNOTHERAPY-
dc.subject.keywordPlusNANOPARTICLES-
dc.subject.keywordPlusI-131-L19SIP-
dc.subject.keywordPlusPHENOTYPE-
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