The pathophysiology of malignant glioma and treatment strategies

恶性胶质瘤的病理生理学和治疗策略

• 批准号: 17390404
• 负责人: KURATSU Jun-ichi
• 金额: $ 10.59万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390404/
• 关键词: malignant glioma; cytokine; MCP-1; IL-6; proteomix; glioma cancer stem cell; molecular targetting therapy; nano-technology; 薬剤抵抗性; 分子標的治療; 血液脳関門; MGMT; 癌幹細胞; グリオーマ; CCR-2; HO-1; CCR-2阻害剤; PEG-Zn-PP; ビリルビン

We have been investigating for three subjects in analysis of malignant glioma cell biology; 1. Identification and functional analysis of cytokines high expressing in malignant glioma cells. 2. Molecular identification of genes and proteins contributing to malignancy in glioma cells. 3. Characterization of glioma cancer stem cells. We have found that several cytokines such as MCP-1 and IL-6 were overexpressed in malignant glioma cells and they contributed to proliferation or invasion of malignant glioma cells. We have analyzed, the genes related to the malignancy of glioma cells using the methods of DNA microarray, DNA tip and proteomix. However it is necessary for furthermore investigation to confirm whether these genes are involved in the signal of the malignancy of glioma cells. We have confirmed that the glioma cancer stem cells established from the patients with glioma had the potential to grow up in the brain of the mouse and have been investigating for the quality of resistance for the tumor therapy such as chemotherapy or radiotherapy.Based on the new discovery we have found in these study, we have been tackling to make up the new molecular targeting therapy such as to block the autocline cytokines loop, to suppress the activating signal in the malignancy of glioma cells. Furthermore we have been trying to establish a new technology to deliver the drug through the blood-brain barrier using the nano-technology. We need furthermore investigation for the application to clinical therapeutical methods in the therapies for glioma patients.

在恶性胶质瘤细胞生物学分析中，我们主要研究了三个方面：1.恶性胶质瘤细胞中高表达细胞因子的鉴定和功能分析。2.胶质瘤细胞恶性相关基因和蛋白的分子鉴定3.脑胶质瘤干细胞的生物学特性。我们发现一些细胞因子如MCP-1和IL-6在恶性胶质瘤细胞中过表达，它们参与了恶性胶质瘤细胞的增殖或侵袭。我们利用DNA微阵列、DNA TIP和蛋白质组等方法分析了与胶质瘤细胞恶性相关的基因。然而，这些基因是否参与了胶质瘤细胞恶性信号的传递还有待进一步的研究。我们已经证实了从脑胶质瘤患者体内培养的胶质瘤干细胞具有在小鼠脑内生长的潜能，并一直在研究其对化疗或放射治疗等肿瘤治疗的耐受性。基于我们在这些研究中发现的新发现，我们一直在致力于构建新的分子靶向治疗方法，如阻断自长跃层细胞因子环，抑制胶质瘤细胞恶性转化中的激活信号。此外，我们一直在尝试建立一种利用纳米技术通过血脑屏障传递药物的新技术。在胶质瘤患者的治疗中，临床治疗方法的应用还需要进一步的研究。

项目成果

Rising incidence of primary central nervous system lymphoma in Kumamoto, Japan

• DOI: 10.1016/j.surneu.2006.05.055
• 发表时间: 2006-11-01
• 期刊: SURGICAL NEUROLOGY
• 作者: Makino, Keishi;Nakamura, Hideo;Kuratsu, Jun-ichi
• 通讯作者: Kuratsu, Jun-ichi

グリオーマにおけるメチオニン、FDG-PETの有用性

蛋氨酸和 FDG-PET 在神经胶质瘤中的作用

• 发表时间: 2007
• 作者: K.;Makino;M.;Kochi;H.;Nakamura;J.;Kuroda;Y.;Honda;Y.;Ushio;J.;Kuratsu;Yano S.et al.;Nakamura H. et al.;Hirano H. et al.;Makino K. et al.;Kawano T. et al.;中村 英夫
• 通讯作者: 中村 英夫

再発脳原発悪性リンパ腫の臨床解析と治療法の検討

复发性原发性脑恶性淋巴瘤的临床分析及治疗方法

• 发表时间: 2006
• 作者: Keishi;Makino;牧野 敬史;Keishi Makino;牧野 敬史
• 通讯作者: 牧野 敬史

Analysis of the treatment results of pediatric low grade astrocytoma at Kumamoto University Hospital,Japan

日本熊本大学医院小儿低度恶性星形细胞瘤治疗结果分析

• 发表时间: 2006
• 作者: Hideo;Nakamura;Keishi Makino
• 通讯作者: Keishi Makino

Evaluation of the treatment of non-germinomatous malignant germ cell tumors-asingle institution study

非生殖细胞恶性生殖细胞肿瘤的治疗评价——单一机构研究

• 发表时间: 2006
• 作者: Hideo;Nakamura;Keishi Makino;Hideo Nakamura
• 通讯作者: Hideo Nakamura