Prognostic significance of forkhead box M1 (FoxM1) expression and antitumour effect of FoxM1 inhibition in melanoma

研究成果: ジャーナルへの寄稿記事

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Aims: Forkhead box M1 (FoxM1) is a transcription factor that regulates cell-cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266-4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1-overexpressing melanoma had significantly shorter survival [both for melanoma-specific survival (MSS) and disease-free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95% confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95% CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.

元の言語英語
ページ(範囲)63-71
ページ数9
ジャーナルHistopathology
69
発行部数1
DOI
出版物ステータス出版済み - 7 1 2016

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Melanoma
Disease-Free Survival
Survival
Thiostrepton
Confidence Intervals
Cell Line
Dacarbazine
Small Interfering RNA
Cell Movement
Neoplasms
Cell Cycle
Transcription Factors
Multivariate Analysis
Cell Proliferation
Staining and Labeling
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

これを引用

@article{7b478c628dca4130bbe2d9178324d545,
title = "Prognostic significance of forkhead box M1 (FoxM1) expression and antitumour effect of FoxM1 inhibition in melanoma",
abstract = "Aims: Forkhead box M1 (FoxM1) is a transcription factor that regulates cell-cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266-4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1-overexpressing melanoma had significantly shorter survival [both for melanoma-specific survival (MSS) and disease-free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95{\%} confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95{\%} CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.",
author = "Takamichi Ito and Kenichi Kouhashi and Yuichi Yamada and Akira Maekawa and Masaaki Kuda and Masutaka Furue and Yoshinao Oda",
year = "2016",
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T1 - Prognostic significance of forkhead box M1 (FoxM1) expression and antitumour effect of FoxM1 inhibition in melanoma

AU - Ito, Takamichi

AU - Kouhashi, Kenichi

AU - Yamada, Yuichi

AU - Maekawa, Akira

AU - Kuda, Masaaki

AU - Furue, Masutaka

AU - Oda, Yoshinao

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Aims: Forkhead box M1 (FoxM1) is a transcription factor that regulates cell-cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266-4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1-overexpressing melanoma had significantly shorter survival [both for melanoma-specific survival (MSS) and disease-free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95% confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95% CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.

AB - Aims: Forkhead box M1 (FoxM1) is a transcription factor that regulates cell-cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266-4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1-overexpressing melanoma had significantly shorter survival [both for melanoma-specific survival (MSS) and disease-free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95% confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95% CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.

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