https://scholars.lib.ntu.edu.tw/handle/123456789/523546
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Lai W.-Y. | en_US |
dc.contributor.author | Chen C.-Y. | en_US |
dc.contributor.author | Yang S.-C. | en_US |
dc.contributor.author | Wu J.-Y. | en_US |
dc.contributor.author | Chang C.-J. | en_US |
dc.contributor.author | PAN-CHYR YANG | en_US |
dc.contributor.author | Peck K. | en_US |
dc.creator | Lai W.-Y.;Chen C.-Y.;Yang S.-C.;Wu J.-Y.;Chang C.-J.;PAN-CHYR YANG;Peck K. | - |
dc.date.accessioned | 2020-12-02T02:33:44Z | - |
dc.date.available | 2020-12-02T02:33:44Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925269097&doi=10.1038%2fmtna.2014.3&partnerID=40&md5=8d9702b1d6da322feeb0f299ffb86c1d | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/523546 | - |
dc.description.abstract | Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the main therapeutic agents used to treat non-small-cell lung cancer patients harboring EGFR-activating mutations. However, most of these patients will eventually develop resistance, 50% of which are due to a secondary mutation at T790M in the EGFR. In this paper, we describe the development of an allele-specific DNAzyme, DzT, that can specifically silence EGFR T790M mutant messenger RNA while leaving wild-type EGFR intact. Allele-specific silencing of EGFR T790M expression and downstream signaling by DzT triggered apoptosis in non-small-cell lung cancer cells harboring this mutant. Adding a cholesterol-triethylene glycol group on the 3′-end of DzT (cDzT) improved drug efficacy, increasing inhibitory effect on cell viability from 46 to 79% in T790M/L858R-harboring H1975TM/LR non-small-cell lung cancer cells, without loss of allele specificity. Combined treatment with cDzT and BIBW-2992, a second-generation EGFR-tyrosine kinase inhibitor, synergistically inhibited EGFR downstream signaling and suppressed the growth of xenograft tumors derived from H1975TM/LR cells. Collectively, these results indicate that the allele-specific DNAzyme, DzT, may provide an alternative treatment for non-small-cell lung cancer that is capable of overcoming EGFR T790M mutantbased tyrosine kinase inhibitor resistance. ? 2014 The American Society of Gene & Cell Therapy All rights reserved. | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.ispartof | Molecular Therapy - Nucleic Acids | - |
dc.subject | DNAzyme; EGFR T790M; NSCLC; TKI | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | afatinib; caspase 3; cholesterol; deoxyribozyme; epidermal growth factor receptor; gefitinib; genomic DNA; messenger RNA; mitogen activated protein kinase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein kinase B; STAT3 protein; triethylene glycol; allele; animal cell; animal experiment; animal model; apoptosis; Article; cancer chemotherapy; cancer gene therapy; cancer inhibition; cancer resistance; cancer survival; cell activation; cell count; cell killing; cell mutant; cell proliferation; cell survival; cell viability; controlled study; dimerization; DNA sequence; drug efficacy; drug potentiation; drug structure; endosome; enzyme phosphorylation; experimental neoplasm; flow cytometry; gene expression; gene silencing; genetic transfection; human; immunoblotting; lung cancer cell line; mouse; non small cell lung cancer; nonhuman; point mutation; priority journal; protein expression; quantitative analysis; reverse transcription polymerase chain reaction; signal transduction; tumor xenograft; wild type | - |
dc.title | Overcoming EGFR T790M-based tyrosine kinase inhibitor resistance with an allele-specific DNAzyme | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1038/mtna.2014.3 | - |
dc.identifier.scopus | 2-s2.0-84925269097 | - |
dc.relation.pages | e150 | - |
dc.relation.journalvolume | 3 | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Clinical Pharmacy | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Biomedical Electronics and Bioinformatics | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.orcid | 0000-0001-6330-6048 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Electrical Engineering and Computer Science | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學系 |
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