Effect of ROCK/Rho-associated kinace inhibitor for malignant gliomas

ROCK/Rho相关激酶抑制剂对恶​​性胶质瘤的作用

• 批准号: 18591583
• 负责人: SAKAI Keiichi
• 金额: $ 1.56万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591583/
• 关键词: Brain Tumor; Gene Therapy; Cytoskeleton; Cell Cycle; 細胞骨格蛋白

The small GTP-binding protein Rho and its target Rho-associated kinase trigger an intracellular signaling cascade that controls actin cytoskeleton and plays an important role in cell motility and adhesion. However, the mechanisms in human glliomas remain poorly understood. The purpose of this study was to investigate the role for the Rho-GTPases in cell motility and invasion of malignant gliomas, and to investigate the glioma activity after administration of the ROCK/Rho-kinase inhibitor. We examined how the inhibition of activation of the ROCK/Rho-kinase inhibitor Y27632 affected astrocyotma molphology, invasion and cell growth. Treatment of glioma cells with the ROCK/Rho-kinase inhibitor resulted in actin cytoskeleton reorganization and in the changed shape and distribution of cells. We observed that the Rho-kinase inhibitor inhibited motility and invasion of glioma cells, suggesting the ROCK-dependent mechanism are important. The results indicated that the ROCK/Rho-kinase inhibitor can suppress glioma activity, including invasion and cell growth, suggesting that the ROCK/Rho-kinase inhibitor may have therapeutic potential in the treatment of malignant gliomas.

小 GTP 结合蛋白 Rho 及其靶标 Rho 相关激酶触发细胞内信号级联，控制肌动蛋白细胞骨架，并在细胞运动和粘附中发挥重要作用。然而，人类神经胶质瘤的机制仍然知之甚少。本研究的目的是探讨 Rho-GTP 酶在恶性胶质瘤细胞运动和侵袭中的作用，并探讨 ROCK/Rho 激酶抑制剂给药后胶质瘤的活性。我们研究了 ROCK/Rho 激酶抑制剂 Y27632 的激活抑制如何影响星形胶质细胞形态、侵袭和细胞生长。用 ROCK/Rho 激酶抑制剂处理神经胶质瘤细胞导致肌动蛋白细胞骨架重组以及细胞形状和分布的改变。我们观察到 Rho 激酶抑制剂抑制神经胶质瘤细胞的运动和侵袭，表明 ROCK 依赖性机制很重要。结果表明ROCK/Rho激酶抑制剂可以抑制胶质瘤活性，包括侵袭和细胞生长，提示ROCK/Rho激酶抑制剂可能在恶性胶质瘤的治疗中具有治疗潜力。

项目成果

神経膠腫におけるLOH解析の検討

胶质瘤中 LOH 分析的考虑

• 发表时间: 2007
• 作者: 酒井 圭一

Analysis of proliferation marker and p53 in skull base chordomas: relationships and prognostic value.

颅底脊索瘤增殖标志物和 p53 分析：关系和预后价值。

• 发表时间: 2007
• 作者: Sakai K

神経膠腫における遺伝子解析:マイクロサテライト法による1p,10q,19qの検討.

神经胶质瘤的遗传分析：使用微卫星方法检查 1p、10q 和 19q。

• 发表时间: 2007
• 作者: 酒井圭一

Loss of Heterozygosity in astocytic tumors

星形细胞肿瘤杂合性缺失

• 发表时间: 2007
• 作者: Sakai; K.; et. al.
• 通讯作者: et. al.

Analysis of immunohistochemical expression of p53 and the expression marker Ki-67 antigen in skull base chordomas : relationships between their expression and prognosis

颅底脊索瘤中p53和表达标记Ki-67抗原的免疫组织化学表达分析：其表达与预后的关系

• 发表时间: 2007
• 作者: Keiichi; Sakai; et. al.
• 通讯作者: et. al.