Prognostic significance of Forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in angiosarcoma

Takamichi Ito, Kenichi Kouhashi, Yuichi Yamada, Takeshi Iwasaki, Akira Maekawa, Masaaki Kuda, Daichi Hoshina, Riichiro Abe, Masutaka Furue, Yoshinao Oda

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.

元の言語英語
ページ(範囲)823-830
ページ数8
ジャーナルJournal of Cancer
7
発行部数7
DOI
出版物ステータス出版済み - 1 1 2016

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Hemangiosarcoma
Disease-Free Survival
Survival
docetaxel
Thiostrepton
Epithelioid Hemangioendothelioma
Confidence Intervals
Cell Line
Kaposi's Sarcoma
Hemangioma
Small Interfering RNA
Cell Cycle
Transcription Factors
Therapeutics
Multivariate Analysis
Cell Proliferation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology

これを引用

Prognostic significance of Forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in angiosarcoma. / Ito, Takamichi; Kouhashi, Kenichi; Yamada, Yuichi; Iwasaki, Takeshi; Maekawa, Akira; Kuda, Masaaki; Hoshina, Daichi; Abe, Riichiro; Furue, Masutaka; Oda, Yoshinao.

:: Journal of Cancer, 巻 7, 番号 7, 01.01.2016, p. 823-830.

研究成果: ジャーナルへの寄稿記事

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title = "Prognostic significance of Forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in angiosarcoma",
abstract = "Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5{\%} vs. 47.1{\%}, P = 0.013; and 5-year EFS, 5.5{\%} vs. 28.7{\%}, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95{\%} confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95{\%}CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.",
author = "Takamichi Ito and Kenichi Kouhashi and Yuichi Yamada and Takeshi Iwasaki and Akira Maekawa and Masaaki Kuda and Daichi Hoshina and Riichiro Abe and Masutaka Furue and Yoshinao Oda",
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TY - JOUR

T1 - Prognostic significance of Forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in angiosarcoma

AU - Ito, Takamichi

AU - Kouhashi, Kenichi

AU - Yamada, Yuichi

AU - Iwasaki, Takeshi

AU - Maekawa, Akira

AU - Kuda, Masaaki

AU - Hoshina, Daichi

AU - Abe, Riichiro

AU - Furue, Masutaka

AU - Oda, Yoshinao

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.

AB - Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.

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DO - 10.7150/jca.14461

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