| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-02-25 |
| タイトル |
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タイトル |
Inhibition of Uterine Sarcoma Cell Growth through Suppression of Endogenous Tyrosine Kinase B Signaling |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 作成者 |
Makino, Kenichi
Kawamura, Kazuhiro
Sato, Wataru
Kawamura, Nanami
Fujimoto, Toshio
Terada, Yukihiro
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| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
Uterine leiomyosarcoma is an aggressive tumor typically found at advanced stages due to difficulties with early diagnosis. Because uterine leiomyosarcoma is resistant to conventional radiation and chemotherapy, the development of more potent medical therapeutics is anticipated. Using quantitative real-time RT-PCR and immunostaining, we found the expression of brain-derived neurotrophic factor (BDNF) and neurotropin-4/5, together with their receptor, tyrosine kinase B (TrkB), in different uterine sarcoma cell lines and primary tumor samples from uterine leiomyosarcoma patients. We noted that levels of BDNF were more abundant than those of neurotropin-4/5. Moreover, the expression of TrkB and its ligands was elevated in a multidrug-resistant cell line and samples obtained from patients with leiomyosarcoma. In cultured uterine sarcoma cells, inhibition of endogenous TrkB signaling by treatment with either the soluble TrkB ectodomain or the Trk receptor inhibitor, K252a, suppressed cell proliferation and increased apoptosis based on cell viability and proliferation, in situ terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling and caspase-3/7 assays, whereas an inactive plasma membrane nonpermeable K252b was ineffective. Correspondingly, treatment with exogenous BDNF increased cell proliferation. In in vivo studies in athymic nude mice bearing multidrug-resistant uterine sarcoma cell tumors, we demonstrate suppression of tumor growth by treatment with K252a, but not K252b, as reflected by decreased cell proliferation and increased levels of apoptosis and caspase-3/7 activities without obvious side effects. Our findings indicated that endogenous signaling of the TrkB pathway contributed to uterine sarcoma cell growth, and inhibition of TrkB signaling in these tumors could provide a novel medical therapy for patients with uterine sarcomas. |
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言語 |
en |
| 出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
en : PLOS ONE
巻 7,
号 7,
発行日 2012
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| 収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1932-6203 |
| 出版者 |
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出版者 |
Public Library of Science |
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言語 |
en |
| 関連情報 |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0041049 |
| 権利情報 |
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権利情報 |
© 2012 Makino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
iA_2022_115.pdf (612.6 kB)
