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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한외과학회 Annals of Surgical Treatment and Research Annals of Surgical Treatment and Research Vol.100 No.3
- 발행연도
- 2021.3
- 수록면
- 127 - 136 (10page)
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초록· 키워드
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Purpose: Papillary thyroid cancer (PTC) has a high incidence of BRAF<SUP>V600E</SUP> mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAF<SUP>V600E</SUP> mutation status in patients with PTC. We investigated how a selective inhibitor of BRAF<SUP>V600E</SUP> PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer.
Methods: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database.
Results: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3.
Conclusion: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF<SUP>V600E</SUP> mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.
Methods: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database.
Results: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3.
Conclusion: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF<SUP>V600E</SUP> mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.
목차
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (30)
참고문헌 신청
원영주 / 2009 / Nationwide Cancer Incidence in Korea, 2003~2005 / Cancer Research and Treatment 41(3):122~131
Jemal A / 2007 / Cancer statistics, 2007 / CA Cancer J Clin 57:43~66
Larson SD / 2007 / Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway / J Am Coll Surg 204:764~773
Zhang L / 2012 / The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto's disease / BMC Cancer 12:610
Teng W / 2006 / Effect of iodine intake on thyroid diseases in China / N Engl J Med 354:2783~2793
Jemal A / 2007 / Cancer statistics, 2007 / CA Cancer J Clin 57:43~66
Larson SD / 2007 / Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway / J Am Coll Surg 204:764~773
Zhang L / 2012 / The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto's disease / BMC Cancer 12:610
Teng W / 2006 / Effect of iodine intake on thyroid diseases in China / N Engl J Med 354:2783~2793
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