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However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D. Methods: All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model. Results: In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P\u003c0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features. Conclusions: Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. 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High Expression of HuR in Cytoplasm, but Not Nuclei, Is Associated with Malignant Aggressiveness and Prognosis in Bladder Cancer
http://hdl.handle.net/10069/31910
http://hdl.handle.net/10069/3191053e7e4e8-6057-43c1-b138-ce8abbf68683
名前 / ファイル | ライセンス | アクション |
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PLoS8_59095.pdf (13.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-05-22 | |||||
タイトル | ||||||
タイトル | High Expression of HuR in Cytoplasm, but Not Nuclei, Is Associated with Malignant Aggressiveness and Prognosis in Bladder Cancer | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Miyata, Yasuyoshi
× Miyata, Yasuyoshi× Watanabe, Shin-ichi× Sagara, Yuji× Mitsunari, Kensuke× Matsuo, Tomohiro× Ohba, Kojiro× Sakai, Hideki |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Introduction: Human antigen R (HuR) regulates the stability of mRNA and is associated with cell proliferation, angiogenesis, and lymphangiogenesis. However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D. Methods: All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model. Results: In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P<0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features. Conclusions: Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. Its expression was associated with angiogenesis, lymphangiogenesis, and expressions of VEGF-A and -C. | |||||
書誌情報 |
PLoS ONE 巻 8, 号 3, p. e59095, 発行日 2013-03-13 |
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出版者 | ||||||
出版者 | Public Library of Science | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19326203 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0059095 | |||||
権利 | ||||||
権利情報 | © 2013 Miyata 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. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLoS ONE, 8(3), e59095; 2013 |