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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 150 - 155 (6page)
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초록· 키워드
오류제보하기
Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor B (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs).
Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.
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등록된 정보가 없습니다.
참고문헌 (31)
참고문헌 신청
Normanno N / 2005 / Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis / Endocr Relat Cancer 12:471~482
Furugaki K / 2011 / Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292 / Clin Exp Metastasis 28:649~659
Itzstein C / 2011 / The regulation of osteoclast function and bone resorption by small GTPases / Small GTPases 2:117~130
Shostak K / 2015 / EGFR and NF-kappaB: partners in cancer / Trends Mol Med 21:385~393
Bivona TG / 2011 / FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR / Nature 471:523~526
Furugaki K / 2011 / Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292 / Clin Exp Metastasis 28:649~659
Itzstein C / 2011 / The regulation of osteoclast function and bone resorption by small GTPases / Small GTPases 2:117~130
Shostak K / 2015 / EGFR and NF-kappaB: partners in cancer / Trends Mol Med 21:385~393
Bivona TG / 2011 / FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR / Nature 471:523~526
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