Annexin A4 is a novel therapeutic target for uterine leiomyosarcoma.
Project/Area Number |
16K11137
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Osaka University |
Principal Investigator |
FUJITA MASAMI 大阪大学, 医学系研究科, 招へい准教授 (60303963)
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Co-Investigator(Kenkyū-buntansha) |
松崎 慎哉 大阪大学, 医学部附属病院, 助教 (00467565)
上田 豊 大阪大学, 医学系研究科, 講師 (10346215)
高田 友美 大阪大学, 医学系研究科, 助教 (30437420)
小林 栄仁 大阪大学, 医学系研究科, 助教 (50614773)
吉野 潔 産業医科大学, 医学部, 教授 (90362730)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | Annexin A4 / プラチナトランスポーター / 子宮平滑筋肉腫 / 抗癌剤耐性 / 中和抗体 |
Outline of Final Research Achievements |
Resistance to platinum drugs remains a significant problem in uterine leiomyosarcoma (LMS). We investigated the role of Annexin A4 (Anx A4) in the resistance to platinum drugs in LMS. The expression of Anx A4 was examined in LMS cell lines using Western blotting analysis. Anx A4 expression was investigated by immunohistochemistry (IHC) using clinical samples of LMS. The IC50 values for cisplatin were measured in SK-LMS parent cells, the SK-LMS-Anx A4-suppressed cell line (SK-LMS-A4 cells), which transfected the Anx A4 siRNA. The expression of Anx A4 was identified in 2 of 3 SK-LMS cells and was identified in 55% (11/20) of the LMS clinical samples using IHC. The IC50 values for cisplatin improved from 17.2 to 9.4 µM in SK-LMS-A4 cells. Significantly more platinum had accumulated in SK-LMS-A4 cells compared to SK-LMS parent cells. These results indicate that expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs in LMS cells.
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Academic Significance and Societal Importance of the Research Achievements |
プラチナ耐性に大きく関わる因子として我々はAnx A4の解析を続けており、卵巣癌や子宮内膜癌において有望な治療標的因子となることを報告している。しかし、予後不良な子宮平滑筋肉腫での解析は行えていなかった。本研究は、Anx A4の発現が子宮平滑筋肉腫にもあることが示し、また卵巣癌や子宮内膜癌と同様に治療標的因子になりうることを示したことで非常に有意義である。 子宮平滑筋肉腫は前述の様に非常に予後不良な疾患であり、Anx A4が有望な治療標的であることが示されたことは子宮平滑筋肉腫に苦しむ患者の予後を改善しうるため、社会的にも貢献できる研究だと考える。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid Uptake2018
Author(s)
Hiramatsu K, Serada S, Enomoto T, Takahashi Y, Nakagawa S, Nojima S, Morimoto A, Matsuzaki S, Yokoyama T, Takahashi T, Fujimoto M, Takemori H, Ueda Y, Yoshino K, Morii E, Kimura T, Naka T
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Journal Title
Cancer Res
Volume: 78
Issue: 2
Pages: 516-27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6)2017
Author(s)
Yoshino K, Kamiura S, Yokoi T, Nakae R, Fujita M, Takemura M, Adachi K, Wakimoto A, Nishizaki T, Shiki Y, Tsutsui T, Kanda Y, Kobayashi E, Hashimoto K, Mabuchi S, Ueda Y, Sawada K, Tomimatsu T, Kimura T
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Journal Title
Cancer Chemother Pharmacol
Volume: 80
Issue: 6
Pages: 1239-47
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of an efficient strategy to improve HPV immunization coverage in Japan2016
Author(s)
Yagi, A. Ueda, Y. Egawa-Takata, T. Tanaka, Y. Morimoto, A. Terai, Y. Ohmichi, M. Ichimura, T. Sumi, T. Murata, H. Okada, H. Nakai, H. Mandai, M. Yoshino, K. Kimura, T. Saito, J. Kudoh, R. Sekine, M. Enomoto, T. Hirai, K. Horikoshi, Y. Takagi, T. Shimura, K.
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Journal Title
BMC Public Health
Volume: 16(1)
Issue: 1
Pages: 1013-1013
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.2016
Author(s)
Egawa-Takata T, Ueda Y, Tanaka Y, Morimoto A, Kubota S, Yagi A, Terai Y, Ohmichi M, Ichimura T, Sumi T, Murata H, Okada H, Nakai H, Mandai M, Yoshino K, Kimura T, Saito J, Kudo R, Sekine M, Enomoto T, Horikoshi Y, Takagi T, Shimura K.
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Journal Title
Int J Clin Oncol.
Volume: 21
Issue: 5
Pages: 962-968
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Japanese Crisis of HPV Vaccination2016
Author(s)
Sekine, M. Kudo, R. Adachi, S. Yamaguchi, M. Ueda, Y. Takata, T. Morimoto, A. Tanaka, Y. Yagi, A. Miyagi, E. Enomoto, T.
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Journal Title
Int J Pathol Clin Res
Volume: 2(2)
Pages: 039-039
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 2',4'bridged nucleic acid antisense for Annexin A4 Improve platinum drug resistance of ovarian2017
Author(s)
Nakagawa S, Yoshino K, Kakubari R, Matsuzaki S, Okazawa A, Matsuzaki S, Kobayashi E, Ueda Y, Naka T, Kimura T
Organizer
第69回日本産科婦人科学会学術講演会
Related Report
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[Presentation] Ex vivo chemosensitivity assay using patient-derived spheroids of epithelial ovarian cancer2017
Author(s)
Ito Y, Kubota S, Kiyohara Y, Endo H, Kondo J, Matsuzaki S, Kimura T, Ueda Y, Yoshino K, Kamiura S, Kimura T, Inoue M
Organizer
第76回日本癌学会学術集会
Related Report
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[Presentation] Disparities in the incidence of HPV 16/18 infections among young females depending on an unfortunate year of birth2016
Author(s)
Tanaka, Y. Ueda, Y. Yagi, A. Takata, T. Matsuzaki, S. Yoshino, K. Satoh, M. Miyagi, E. Enomoto, T. Nakayama, T. Morii, E. Kimura, T.
Organizer
第75回日本癌学会学術集会
Place of Presentation
横浜
Year and Date
2016-10-06
Related Report
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[Presentation] Lipolysis-stimulated lipoprotein receptor(LSR)can be a new therapeutic target for ovarian cancer.2016
Author(s)
Satoko, M. Hiramatsu, K. Serata, S. Nakagawa, S. Shinya, M. Fujimoto, Y. Ueda, Y. Yoshino, K. Enomoto, T. Kimura, T. Naka, T.
Organizer
第75回日本癌学会学術集会
Place of Presentation
横浜
Year and Date
2016-10-06
Related Report
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[Presentation] Anti-LSR monoclonal antibody inhibits ovarian cancer growth via inhibition of lipid metabolism2016
Author(s)
Hiramatsu, K. Yoshino, K. Enomoto, T. Nakagawa, S. Morimoto, A. Yokoyama, T. Amemiya, K. Matsuzaki, S. Kobayashi, E. Ueda, Y. Naka, T. Kimura, T.
Organizer
第68回日本産科婦人科学学会学術講演会
Place of Presentation
東京
Year and Date
2016-04-21
Related Report
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[Presentation] “Smartscopy” as a new device to identify the precancerous diseases of the uterine cervix : a pilot study2016
Author(s)
Tanaka, Y. Ueda, Y. Kakuda, M. Kubota, S. Matsuzaki, S. Nakagawa, S. Takata, T. Matsuzaki, S. Kobayashi, E. Yoshino, K. Kimura, T.
Organizer
第68回日本産科婦人科学学会学術講演会
Place of Presentation
東京
Year and Date
2016-04-21
Related Report
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[Presentation] Lipolysis-stimulated lipoprotein receptor (LSR) can be a new therapeutic target of ovarian cancer.2016
Author(s)
Satoko, M. Hiramatsu, K. Serada, S. Nakagawa, S. Shinya, M. Ueda, Y. Fujimoto, M. Yoshino, K. Kimura, T. Naka, T.
Organizer
The 107th Annual Meeting of the American Association for Cancer Research
Place of Presentation
New Orleans, U.S.A.
Year and Date
2016-04-16
Related Report
Int'l Joint Research
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