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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 27 - 32 (6page)
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Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells.
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참고문헌 (24)
참고문헌 신청
Sharma SV / 2007 / Epidermal growth factor receptor mutations in lung cancer / Nat Rev Cancer 7:169~181
Ciardiello F / 2001 / A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor / Clin Cancer Res 7:2958~2970
Tam IY / 2006 / Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features / Clin Cancer Res 12:1647~1653
Riely GJ / 2006 / Update on epidermal growth factor receptor mutations in nonsmall cell lung cancer / Clin Cancer Res 12:7232~7241
Paez J / 2004 / EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy / Science 304:1497~1500
Ciardiello F / 2001 / A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor / Clin Cancer Res 7:2958~2970
Tam IY / 2006 / Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features / Clin Cancer Res 12:1647~1653
Riely GJ / 2006 / Update on epidermal growth factor receptor mutations in nonsmall cell lung cancer / Clin Cancer Res 12:7232~7241
Paez J / 2004 / EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy / Science 304:1497~1500
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