Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma
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- Masahiro Yamamoto
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Tomomi Sanomachi
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Shuhei Suzuki
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Hiroyuki Uchida
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Hajime Yonezawa
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Nayuta Higa
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Tomoko Takajo
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Yuki Yamada
- Neurosurgery, Yamagata University School of Medicine, Yamagata, Japan
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- Asuka Sugai
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Keita Togashi
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Shizuka Seino
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Masashi Okada
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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- Yukihiko Sonoda
- Neurosurgery, Yamagata University School of Medicine, Yamagata, Japan
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- Hirofumi Hirano
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Koji Yoshimoto
- Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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- Chifumi Kitanaka
- Departments of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan
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<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.</jats:p></jats:sec>
収録刊行物
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- Neuro-Oncology
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Neuro-Oncology 23 (6), 945-954, 2021-02-08
Oxford University Press (OUP)
