Functional analysis and molecular target therapeutic establishment of Survivin in malignant glioma
| Project/Area Number |
16591441
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
SUGIYAMA Kazuhiko Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (30243554)
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| Co-Investigator(Kenkyū-buntansha) |
KURISU Kaoru Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (70201473)
ARITA Kazunori Kagoshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (90212646)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | survivin / malignant glioma / p53 / radiosensitivity / molecular targeted therapy / localization / prognosis / 悪性グリオーマ / 核分裂異常 / 放射線療法 / 化学療法 / ACNU / survivin / RNA i / apoptosis |
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| Research Abstract |
Survivin has multifunction which is involved in the anti-apoptotic function and the regulation of mitosis. We have previously reported that the expression of Survivin mRNA correlated with the malignant grade and prognosis of patients with gliomas. Therefore, we expected that Survivin could be a target of molecular targeted therapy in malignant gliomas. We found that suppression of survivin led to the increase of aneuploid cells due to inhibition of proper chromosomal segregation in malignant glioma cell liens : U251MG cells (p53, mutant type) and D54MG cells (p53, wild type). Then, we examine the influence of Survivin suppression on radiosensitivity in the early phase (during 5 days) and the late phase (during 14 days). Survivin suppression increased radiosensitivity in both cell lines in the late phase but in only U251MG cells in the early phase. These results suggest that the dysfunction of p53 may have some interaction with the dysfunction of survivin. From our observations, it seem
… More
s that Survivin can be an effective target of molecular targeted therapy to increase the radiosensitivity in malignant gliomas, influenced by p53 status.
Furthermore, we examined the expression of Survivin in our clinical samples with malignant gliomas. We immunohistochemically examined the pattern of subcellular localization of Survivin expression in 51 patients, categorizing into 3 groups : nuclear-positive group (only nucleus positive), cytoplasmic-positive group (only cytoplasm positive), and nuclear-cytoplasmic group (both nucleus and cytoplasm positive). We statistically examined the relationship between survivin localization and prognosis. All specimens stained positive for Survivin : localized in nucleus only, 10 cases ; localized in cytoplasm only, 23 cases ; simultaneous expression in nucleus and cytoplasm, 19 cases. The nuclear-cytoplasmic group had significantly shorter overall survival than the nuclear-positive group and the cytoplasmic-positive group. We found that simultaneous expression of survivin in both the nucleus and cytoplasm increased the treatment resistance of malignant gliomas. Less
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Report
(3 results)
Research Products
(41 results)
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[Journal Article] 神経鞘腫2005
Author(s)
梶原佳則
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Journal Title
脳腫瘍の診断と治療-最近の動向-III. 脳腫瘍の病理 分類(日本臨床)
Pages: 139-144
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] 胎児性腫瘍2004
Author(s)
栗栖 薫
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Journal Title
脳神経外科学大系 脳腫瘍I(吉田 純、 山浦 昌)
Pages: 418-434
Description
「研究成果報告書概要(和文)」より
Related Report
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