Academic Journal
Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor.
العنوان: | Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor. |
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المؤلفون: | Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Tomoya Matsunobu, Ken-Ichi Kawaguchi, Nokitaka Setsu, Keiichiro IIda, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima |
المصدر: | PLoS ONE, Vol 12, Iss 5, p e0178064 (2017) |
بيانات النشر: | Public Library of Science (PLoS), 2017. |
سنة النشر: | 2017 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | BACKGROUND:Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear. METHODS:The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α. RESULTS:The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis. CONCLUSION:Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | http://europepmc.org/articles/PMC5448771?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0178064 |
URL الوصول: | https://doaj.org/article/084c76af444e480481615064fed28b09 |
رقم الانضمام: | edsdoj.084c76af444e480481615064fed28b09 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0178064 |