Mechanisms underlying inhibition of tumor-immunology in malignant glioma and development of immune-activation therapy using suicide-chimeric molecule

恶性胶质瘤肿瘤免疫抑制机制及自杀嵌合分子免疫激活疗法的开发

• 批准号: 17390405
• 负责人: TAKESHIMA Hideo
• 金额: $ 10.5万
• 依托单位: University of Miyazaki (2006-2007)Kumamoto University (2005)
• 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-17390405/
• 关键词: malignant glioma; tumor immunology; MCP-1; TGF-[○!R]; ABCA2; oligodendroglioma; グリオーマ; TGF-b

Malignant glioma is the most malignant tumor of the human neoplasms. Despite extensive clinical trials, a good clinical outcome has remained an elusive goal. The success of treatment is hampered by factors such as high degree of infiltration, resistance against irradiation and anti-cancer drugs, and existence of the blood brain barriers that inhibit the drug delivery into the central nervous system. In addition, it has been postulated that immuno-suppressive molecules produced by the tumor cells inhibit the establishment of the anti-tumor immunity such as TGF-β.In this project, we initially investigated the correlation between the expression of TGF-β and prognosis of the patients with malignant glioma using tissue microarray. However, we failed to show the statistical significance between them. To search for the novel immuno-suppressant produced by the malignant glioma, we investigated the molecules that were specifically expressed by the anaplastic oligodendroglioma, which is malignant but has good prognosis.Among these molecules, we focused on ABCA2, a membranous protein. Quantitative real-time PCR, immunoblot and immunohistochemical study demonstrated that ABCA2 is highly expressed in oligodendroglial tumors than in astrocytic tumors. Although biological role on the tumor immunology is still under investigation, it is interesting that ABCA2 could serve as a novel tumor marker for oligodendrogliomas.

恶性胶质瘤是人类恶性程度最高的肿瘤。尽管进行了广泛的临床试验，但良好的临床结局仍然是一个难以实现的目标。治疗的成功受到诸如高度浸润、对辐射和抗癌药物的抗性以及抑制药物递送到中枢神经系统的血脑屏障的存在等因素的阻碍。此外，肿瘤细胞产生的免疫抑制分子抑制了抗肿瘤免疫的建立，如TGF-β。本课题利用组织芯片技术初步探讨了TGF-β表达与恶性胶质瘤患者预后的关系。然而，我们未能显示它们之间的统计学显着性。为了寻找恶性胶质瘤产生的新的免疫抑制剂，我们研究了恶性但预后良好的间变性少突胶质细胞瘤特异性表达的分子，其中ABCA 2是一种膜蛋白。实时荧光定量PCR、免疫印迹和免疫组化研究表明ABCA 2在少突胶质细胞瘤中的表达高于星形细胞瘤。尽管ABCA 2在肿瘤免疫学中的生物学作用仍在研究中，但有趣的是，ABCA 2可以作为少突胶质细胞瘤的新肿瘤标志物。

项目成果

Coexpression of c-kit and SCF in CNS germ cell tumors

CNS 生殖细胞肿瘤中 c-kit 和 SCF 的共表达

• 发表时间: 2005
• 作者: Takeshima;H.;Uchida;H.;Yunoue;S.;Nakamura;H.;Kuratsu;J
• 通讯作者: J

Single Nucleotide Polymorphism 309 Affects Murin-Double-Minute 2 Protein Expression But Not Glioma Tumorigenesis

单核苷酸多态性 309 影响 Murin-Double-Minute 2 蛋白表达，但不影响神经胶质瘤肿瘤发生

• 发表时间: 2007
• 期刊: Neurologia medico-chirurgica 47(5)
• 作者: S.;Obara;M.;Nakata;H.;Takeshima;K.;Arita;N.;Inagaki;J.;Kuratsu;Hideo Nakamura;Keishi Makino;Keishi Makino;Hiromasa Tsuiki
• 通讯作者: Hiromasa Tsuiki

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

Coexpression of c-kit and SCF germ cell tumors

c-kit 和 SCF 生殖细胞肿瘤的共表达

• 发表时间: 2005
• 作者: Takeshima;H.;Obara;S.;Kuratsu;J;Takeshima H
• 通讯作者: Takeshima H

Role of Kunitz domains in anti-invasive effect of hepatocyte growth factor activator inhibitor type 1 in human glioblastoma cells

Kunitz结构域在肝细胞生长因子激活剂抑制剂1型人胶质母细胞瘤细胞抗侵袭作用中的作用

• 发表时间: 2007
• 期刊: Human Cell 20
• 作者: Miyata;S.;Fukushima;T.;Kohama;K.;Tanaka;H.;Takeshima;H.;Kataoka;H
• 通讯作者: H