Molecular genetic analysis and establishment of tailor-maid therapy for malignant brain tumors.

恶性脑肿瘤的分子遗传学分析及量身定制疗法的建立。

基本信息

  • 批准号:
    12671345
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2001
  • 项目状态:
    已结题

项目摘要

We have studied genetic alterations of several oncogenes and suppressor-oncogenes including TP53, INK4a/ARF, MDM2, BCL10, DcR3, and so on, in the point of clinical aspects. Resent development of nucleotide-array advanced the frontier of gene analyzes. In this research project, we investigated a series of 91 patients with malignant brain tumors including astrocytic tumors, intracranial germ cell tumors (ICGTs), and primary central nervous system lymphomas (PCNSLs) to determine genetic alterations of various genes. And we are going to make use of the obtained-results for establishing a tailor-made therapy based on array system. The following three results were obtained in this project term.1) Decoy receptor 3 (DcR3), negative regulator of Fas-mediated apoptosis, was amplified in 0 of 7 (0 %) low grade astrocytomas, 1 of 16 (6.3 %) anaplastic astrocytomas, and 7 of 34 (20.6 %) glioblastoma multiformes. These results suggest that the gene amplification is responsible for malignant features in high grade astrocytic tumors.2) While no inactivating mutations of BCL10 gene were found, many germinoma (5 of 10 germinoma : 50 %), had specific single nucleotide polymorphism (SNP) in exonl of BCL10. This SNP was found at significantly higher frequency in the Japanese population than in other population worldwide (p < 0.0001). The specific SNP in the BCL10 gene may be partly responsible for Japanese propensity of ICGTS.3) INK4a / ARF gene showed an alteration of homozygous deletion at a high frequency (9 of 14 : 64%) in patients with PCNSLs. The alteration was related with bcl-2 anti-apoptotic protein overexpression as well as shorter patient survival. This study suggeststhat the INK4a / ARF gene homozygous deletion and overexpression of the bcl-2 protein may serve as important predictors for prognosis of patients with PCNSLs.Making use of above mentioned results, we are going to check the accuracy of our gene-array system and develop it.
我们从临床角度研究了TP53、INK4a/ARF、MDM2、Bcl10、DcR3等癌基因和抑癌基因的遗传变化。近年来,核苷酸芯片的发展推动了基因分析的前沿。在这项研究中,我们调查了91例恶性脑肿瘤患者,包括星形细胞肿瘤、颅内生殖细胞肿瘤(ICGTs)和原发性中枢神经系统淋巴瘤(PCNSLs),以确定各种基因的遗传变化。我们将利用已有的成果,建立基于阵列系统的量身定制的治疗方法。1)低级别星形细胞瘤7例(0%),间变性星形细胞瘤16例(6.3%),多形性胶质母细胞瘤7例(20.6%),诱骗受体3(DcR3)是Fas介导的细胞凋亡负调控因子。2)在未发现Bcl10基因失活突变的情况下,许多生殖细胞瘤(5/10,50%)在Bcl10基因外显子上存在特异性单核苷酸多态性(SNP)。这种单核苷酸多态性在日本人群中的出现频率明显高于全球其他人群(p&lt;0.0001)。3)INK4a/ARF基因在PCNSLS患者中表现出高频率的纯合子缺失改变(9/14:%)。这种改变与bcl2抗凋亡蛋白过度表达及患者生存期缩短有关。本研究提示,INK4a/ARF基因纯合缺失和bcl2蛋白过表达可能是预测PCNSL患者预后的重要指标。利用上述结果,我们将检验我们的基因阵列系统的准确性并开发它。

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hayashi Y et al.: "Homozygous deletion of INK4a/ARF gones and overexpression of bbd-2 in relation with poor prognosis in immunocompetent patients with primary control nervous system lymphoma of the diffuse large B cell type"Journal of Neuro Oncology. 55.
Hayashi Y 等人:“INK4a/ARF 纯合缺失和 bbd-2 过度表达与免疫功能正常的弥漫性大 B 细胞型原发性控制神经系统淋巴瘤患者预后不良有关”《神经肿瘤学杂志》。
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    0
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Iwato M et al.: "Molecular analysis for p53 and mdm2 in intracranial germ cell tumors"Acta Neuropathol. 99. 21-25 (2000)
Iwato M 等人:“颅内生殖细胞肿瘤中 p53 和 mdm2 的分子分析”Acta Neuropathol。
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    0
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Hayashi.Y, et al.: "Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma multiforme a molealar genetic analysis"Journal of Neuro Surgery. 95. 138-142 (2001)
Hayashi.Y 等人:“神经节细胞瘤/神经节胶质瘤恶性转化为多形性胶质母细胞瘤,摩尔遗传分析”神经外科杂志。
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    0
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Y Hayashi, M Iwato, M Hasegawa, O Tachibana, A von Deimling, J Yamashita: "Malignant transformation of a gangliocytoma / ganglioglioma into a glioblastoma multiforme: A molecular genetic analysis"J Neurosurg. 95. 138-142 (2001)
Y Hayashi、M Iwato、M Hasekawa、O Tachibana、A von Deimling、J Yamashita:“神经节细胞瘤/神经节胶质瘤向多形性胶质母细胞瘤的恶性转化:分子遗传学分析”J Neurosurg。
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    0
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M Iwato, O Tachibana, Y Thoma, H Nitta, Y Hayashi, J Yamashita: "Molecular analysis for p53 and mdm2 in intracranial gem cell tumors"Acta Neuropathol. 99. 21-25 (2000)
M Iwato、O Tachibana、Y Thoma、H Nitta、Y Hayashi、J Yamashita:“颅内宝石细胞肿瘤中 p53 和 mdm2 的分子分析”Acta Neuropathol。
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HAYASHI Yutaka其他文献

HAYASHI Yutaka的其他文献

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{{ truncateString('HAYASHI Yutaka', 18)}}的其他基金

Role and contribution of rural society for peacebuilding
农村社会对建设和平的作用和贡献
  • 批准号:
    16H07365
  • 财政年份:
    2016
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Can tsunami be monitored from the space? -Tsunami detectability of the satellite altimetry mission
可以从太空监测海啸吗?
  • 批准号:
    20510173
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Genetic analysis of glioblastoma cancer stem cell with special reference to chronological and spatial change
胶质母细胞瘤干细胞的遗传分析,特别参考时间和空间变化
  • 批准号:
    20591708
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular Characterization of Patched-associated Rhabdomyosarcoma by Conditional Gene Targeting
通过条件基因靶向对斑块相关横纹肌肉瘤进行分子表征
  • 批准号:
    15390319
  • 财政年份:
    2003
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Identification of neuroblastoma associating genes and application of medical treatment using gene manipulation in an individual
神经母细胞瘤相关基因的鉴定以及利用基因操作在个体中的医疗应用
  • 批准号:
    12470164
  • 财政年份:
    2000
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Deletion mapping of chromosome band 14q32 for isolation and characterization of the putative tumor related gene in human neuroblastoma
染色体带 14q32 的缺失图谱,用于分离和表征人神经母细胞瘤中假定的肿瘤相关基因
  • 批准号:
    09470386
  • 财政年份:
    1997
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
SIGNIFICANCE OF NEUROPEPTIDE Y IN EARLY DIAGNOSIS AND PATHOGENETIC ANALYSIS OF NEUROBLASTOMA
神经肽Y在神经母细胞瘤早期诊断和发病机制分析中的意义
  • 批准号:
    06454503
  • 财政年份:
    1994
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Hyperplasia of distal airway epithelium due to aging among residents in the area where the incidence of lung cancer is high.
肺癌高发地区居民因老龄化导致远端气道上皮增生。
  • 批准号:
    03454165
  • 财政年份:
    1991
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
SIGNIFICANCE OF NEUROPEPTIDE Y IN EARLY DIAGNOSIS AND AS A PROGNOSTIC FACTOR OF NEUROBLASTOMA
神经肽 Y 在早期诊断中的意义以及作为神经母细胞瘤预后因素的意义
  • 批准号:
    03670577
  • 财政年份:
    1991
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
フローサイトメトリーによる小児癌の悪性度の判定と抗癌剤スクリーニングに関する研究
流式细胞术判断儿童癌症恶性程度及抗癌药物筛选研究
  • 批准号:
    61570601
  • 财政年份:
    1986
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

Gene alterations and anti-tumor immunity
基因改变和抗肿瘤免疫
  • 批准号:
    17K18388
  • 财政年份:
    2017
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Establishment of novel assay methods for translocation type gene alterations.
建立易位型基因改变的新测定方法。
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    25670183
  • 财政年份:
    2013
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Telomere elongation mechanisms by ATRX/DRXX gene alterations and their clinical application
ATRX/DRXX基因改变的端粒延长机制及其临床应用
  • 批准号:
    25861670
  • 财政年份:
    2013
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    $ 2.18万
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    Grant-in-Aid for Young Scientists (B)
Development of a novel diagnostic system using next-generation sequencing for targetable gene alterations in lung cancer
使用下一代测序开发肺癌靶向基因改变的新型诊断系统
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    25461179
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    2013
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Prediction of therapy effects and cancer susceptibility for lung cancers by combined data of histology, polymorphism and gene alterations
通过组织学、多态性和基因改变的综合数据预测肺癌的治疗效果和癌症易感性
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口腔癌体细胞基因改变模式
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    7023849
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Patterns of Somatic Gene Alterations in Oral Cancer
口腔癌体细胞基因改变的模式
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  • 财政年份:
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Patterns of Somatic Gene Alterations in Oral Cancer
口腔癌体细胞基因改变的模式
  • 批准号:
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  • 财政年份:
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Patterns of Somatic Gene Alterations in Oral Cancer
口腔癌体细胞基因改变模式
  • 批准号:
    7640283
  • 财政年份:
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Patterns of Somatic Gene Alterations in Oral Cancer
口腔癌体细胞基因改变模式
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    7662655
  • 财政年份:
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