Induced Phenotype Targeted Therapy: Radiation-Induced Apoptosis-Targeted Chemotherapy
DC Field | Value | Language |
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dc.contributor.author | Lee, Beom Suk | - |
dc.contributor.author | Cho, Yong Woo | - |
dc.contributor.author | Kim, Gui Chul | - |
dc.contributor.author | Lee, Do Hee | - |
dc.contributor.author | Kim, Chang Jin | - |
dc.contributor.author | Kil, Hee Seup | - |
dc.contributor.author | Chi, Dae Yoon | - |
dc.contributor.author | Byun, Youngro | - |
dc.contributor.author | Yuk, Soon Hong | - |
dc.contributor.author | Kim, Kwangmeyung | - |
dc.contributor.author | Kim, In-San | - |
dc.contributor.author | Kwon, Ick Chan | - |
dc.contributor.author | Kim, Sang Yoon | - |
dc.date.accessioned | 2021-06-22T20:24:42Z | - |
dc.date.available | 2021-06-22T20:24:42Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2015-02 | - |
dc.identifier.issn | 0027-8874 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/18860 | - |
dc.description.abstract | Background: Tumor heterogeneity and evolutionary complexity may underlie treatment failure in spite of the development of many targeted agents. We suggest a novel strategy termed induced phenotype targeted therapy (IPTT) to simplify complicated targets because of tumor heterogeneity and overcome tumor evolutionary complexity. Methods: We designed a caspase-3 specific activatable prodrug, DEVD-S-DOX, containing doxorubicin linked to a peptide moiety (DEVD) cleavable by caspase-3 upon apoptosis. To induce apoptosis locally in the tumor, we used a gamma knife, which can irradiate a very small, defined target area. The in vivo antitumor activity of the caspase-3-specific activatable prodrug combined with radiation was investigated in C3H/HeN tumor-bearing mice (n = 5 per group) and analyzed with the Student's t test or Mann-Whitney U test. All statistical tests were two-sided. We confirmed the basic principle using a caspase-sensitive nanoprobe (Apo-NP). Results: A single exposure of radiation was able to induce apoptosis in a small, defined region of the tumor, resulting in expression of caspase-3. Caspase-3 cleaved DEVD and activated the prodrug. The released free DOX further activated DEVD-S-DOX by exerting cytotoxic effects on neighboring tumor or supporting cells, which repetitively induced the expression of caspase-3 and the activation of DEVD-S-DOX. This sequential and repetitive process propagated the induction of apoptosis. This novel therapeutic strategy showed not only high efficacy in inhibiting tumor growth (14-day tumor volume [mm(3)] vs radiation alone: 848.21 +/- 143.24 vs 2511.50 +/- 441.89, P < .01) but also low toxicity to normal cells and tissues. Conclusion: Such a phenotype induction strategy represents a conceptually novel approach to overcome tumor heterogeneity and complexity as well as to substantially improve current conventional chemoradiotherapy with fewer sequelae and side effects. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS INC | - |
dc.title | Induced Phenotype Targeted Therapy: Radiation-Induced Apoptosis-Targeted Chemotherapy | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cho, Yong Woo | - |
dc.identifier.doi | 10.1093/jnci/dju403 | - |
dc.identifier.scopusid | 2-s2.0-84925546961 | - |
dc.identifier.wosid | 000351295700003 | - |
dc.identifier.bibliographicCitation | JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, v.107, no.2, pp.1 - 9 | - |
dc.relation.isPartOf | JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | - |
dc.citation.title | JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | - |
dc.citation.volume | 107 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 9 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | STEREOTACTIC RADIOSURGERY | - |
dc.subject.keywordPlus | INTRATUMOR HETEROGENEITY | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | DOXORUBICIN | - |
dc.subject.keywordPlus | CASPASES | - |
dc.subject.keywordPlus | TISSUE | - |
dc.subject.keywordPlus | EVOLUTION | - |
dc.subject.keywordPlus | PROTEASES | - |
dc.subject.keywordPlus | TOXICITY | - |
dc.identifier.url | https://academic.oup.com/jnci/article/107/2/dju403/900218 | - |
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