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The pathophysiology of malignant glioma and of treatment strategies

恶性胶质瘤的病理生理学和治疗策略

基本信息

批准号：
14370439
负责人：
KURATSU Jun-ichi
金额：
$ 8.96万
依托单位：
Kumamoto University (2004)Kagoshima University (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

1.Vascular endothelial growth factor(VEGF) play an important role in the angiogenesis of glioma. We found that there are two mechanisms of angiogenesis by VEGF in malignant glioma, one is via VEGF produced by macrophages infiltrated by monocyte chemoattractant protein 1(MCP-1) derived from glioma cells and the other is via VEGF stimulated by thrombin converted from pro-thrombin derived from glioma cells. Furthermore, we found that docosahexaenoic acid contained in the necrotic tissue suppressed the antitumor activity of macrophages infiltrated in the glioma.2.We reported that the increased activity and expression of Integrin-linked kinase(ILK) activity is regulated by PTEN. The transfection into the glioblastoma cells altered the localization of ILK in the cell membrane ; transfection with PTEN down-regulated PKB/Akt phosphorylation of ILK-singnaling. We assume that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The COX-2 inhibitor was capable of down-regulating ILK and PKB/Akt phosphorylation.3.We retrospectively analyzed the relationship between treatment outcomes and EGF-R gene, homozygous deletion of p16 gene in newly diagnosed glioblastoma adult patients. We found that EGF-R and homozygous deletion of p16 gene are of significant prognostic value for predicting survival in glioblastoma patients.4.Neurofibromin which is a NF1 gene product. We found the mutural regulation of cellular neurofibromin is essential for normal neuronal differentiation and that abnormal regulation in neuronal cells may be implicated in NF1-related learning and memory disturbance.

1.血管内皮生长因子（VEGF）在胶质瘤的血管生成中发挥重要作用。我们发现VEGF在恶性胶质瘤中的血管生成有两种机制，一种是通过胶质瘤细胞来源的单核细胞趋化蛋白1（MCP-1）浸润巨噬细胞产生VEGF，另一种是通过胶质瘤细胞来源的凝血酶原转化为凝血酶刺激VEGF。此外，我们发现坏死组织中含有的二十二碳六烯酸抑制了胶质瘤中浸润的巨噬细胞的抗肿瘤活性。2.我们报道了整合素连接激酶（ILK）活性的增加和表达受PTEN的调节。转染到胶质母细胞瘤细胞中改变了ILK在细胞膜中的定位;转染PTEN下调了ILK信号转导的PKB/Akt磷酸化。我们假设ILK对PKB/Akt依赖性细胞存活的PTEN敏感性调节至关重要。考克斯-2抑制剂能够下调ILK和PKB/Akt磷酸化。3.回顾性分析新诊断成人胶质母细胞瘤患者EGF-R基因、p16基因纯合性缺失与治疗结局的关系。我们发现EGF-R和p16基因的纯合性缺失对胶质母细胞瘤患者的预后有重要的预测价值。我们发现细胞神经纤维蛋白的相互调节是神经元正常分化所必需的，并且神经元细胞中的异常调节可能与NF 1相关的学习和记忆障碍有关。

项目成果

期刊论文数量（64）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurofibromatosis type I tumor suppressor neurofibromin regulates neuronal differentiation via its GAP function toward Ras.

神经纤维瘤病 I 型肿瘤抑制神经纤维蛋白通过其针对 Ras 的 GAP 功能调节神经元分化。

DOI：
发表时间：
2003
期刊：
J.Biol.Chem. 278
影响因子：
0
作者：
S.Yunoue;H.Tokuo;K.Fukunaga;L.Feng;T.Ozawa;T.Nishi;A.Kikuchi;S.Hattori;J.Kuratsu;H.Saya;N.Araki
通讯作者：
N.Araki

N.Shinojima: "Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme."Cancer Res.. 63・20. 6962-6970 (2003)

N.Shinojima：“表皮生长因子受体对多形性胶质母细胞瘤患者的预后价值”。Cancer Res.63・20（2003）。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Expression and distribution of c-kit receptor and its ligand in human CNS germ cell tumors : a useful histological marker for the diagnosis of germinoma.

c-kit受体及其配体在人中枢神经系统生殖细胞肿瘤中的表达和分布：诊断生殖细胞瘤的有用组织学标志物。

DOI：
发表时间：
2004
期刊：
Brain Tumor Pathology 21
影响因子：
0
作者：
Youichi Saitoh;富永篤;有田和徳;Kato Amami;Eguchi Yutaka;Arita K;Saitoh Y;富永篤;Saitoh Y;Tomishima T;有田和徳;Yenomas DC;Soichi Obara;Kanou Y;二宮宏智;Arita K;Hideo Takeshima
通讯作者：
Hideo Takeshima

Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1.

与神经纤维瘤病相关的毛细胞型星形细胞瘤基因改变的初步观察1.