Development of new strategies for cancer treatment based in system biological-analysis of cancer system abnormality

基于癌症系统异常的系统生物学分析开发癌症治疗新策略

• 批准号: 15390439
• 负责人: TABUCHI Kazuo
• 金额: $ 8.96万
• 依托单位: Saga University (2004)佐賀医科大学 (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390439/
• 关键词: glioma; array-CGH; SELDI-TOF MS; detrended fluctuation analysis; pleiotrophin; transthyretin; systems biology; scale-free network; 脳腫瘍; データベース; インターフェロン; トランスクリプトーム; システム生物学; SELDI-TOF mass spectrometry

The purpose of this research is to develop the new strategies of cancer treatment based on systems biological analysis of cancer system abnormality. New genomic aberrations were found in glioblastoma cells by microarray-based comparative genomic hybridization. The first attempts to apply detrended fluctuation analysis to copy number profiles by considering the reading direction as the time axis demonstrated that higher long-term fractal scaling exponents correlated well with longer survival of glioblastoma patients. Proteomic technique using both SELDI-TOF MS(surface enhanced laser desorption/ionization time-of-flight mass spectrometry) and MALDI(matrix assisted laser desorption/ionization) TOF MS identified pleiotrophin as a specific growth factor of neural stem cells and transthyretin as a brain ischemia-specific protein. Petri-Net simulation demonstrated that trimer formation of soluble FasL is essential to enhance apoptotic enhancing activity. The four molecular mechanisms of biological robustness such as redundancy, diversity, feedback, modularity and decoupling were found in glioblastoma biomolecular system. Molecular connection network established by PathwayAssist software had the characteristics of scale-free networks such as existence of hub, obligation of power law, so-called small world and bow-tie structure. The intentional attack to hub protein/subsystem seems to easily destroy the scale-free network of cancer.

本研究的目的是通过对肿瘤系统异常的系统生物学分析，探索肿瘤治疗的新策略。通过基于微阵列的比较基因组杂交，在胶质母细胞瘤细胞中发现了新的基因组畸变。第一次尝试通过考虑阅读方向作为时间轴将去趋势波动分析应用于拷贝数概况，证明了较高的长期分形标度指数与胶质母细胞瘤患者的较长生存期良好相关。采用SELDI-TOF MS（表面增强激光解吸/电离飞行时间质谱）和MALDI（基质辅助激光解吸/电离）TOF MS的蛋白质组学技术鉴定了多效生长因子为神经干细胞的特异性生长因子和甲状腺素运载蛋白为脑缺血特异性蛋白。Petri-Net模拟表明可溶性FasL的三聚体形成对于增强凋亡增强活性是必不可少的。在胶质母细胞瘤生物分子系统中发现了冗余性、多样性、反馈性、模块性和解耦性等四种生物鲁棒性的分子机制。利用PathwayAssist软件建立的分子连接网络具有无标度网络的特点，如枢纽的存在、幂律约束、所谓的小世界和蝴蝶结结构等。对中心蛋白/子系统的攻击似乎很容易破坏癌症的无标度网络。

项目成果

Expression of the Wilms'tumor gene product WT1 in glioblastomas and medullobalstomas

维尔姆斯肿瘤基因产物 WT1 在胶质母细胞瘤和髓母细胞瘤中的表达

• 发表时间: 2004
• 期刊: Brain Tumor Pathology 21
• 作者: Okamoto H;Mineta T;Ueda S;Nakahara Y;Shiraishi T;Tamiya T;Tabuchi K;Okamoto H.;Shiraishi T;Ueda S;Nakahara Y;Nakahara Y
• 通讯作者: Nakahara Y

悪性グリオーマ発生の分子機序

恶性胶质瘤发生的分子机制

• 发表时间: 2005
• 期刊: 脳外誌 14
• 作者: Malchinhuu E;Sato K;Horiuchi Y;Mogi C;Ishiuchi S et al.;田渕和雄
• 通讯作者: 田渕和雄

Increased cytotoxicity of soluble Fas ligand by fusing isoleucine zipper motif

• DOI: 10.1016/j.bbrc.2004.07.098
• 发表时间: 2004-09-10
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Shiraishi, T;Suzuyama, K;Nagata, S
• 通讯作者: Nagata, S

Genetic alterations of human brain tumors as molecular prognostic factors.

人类脑肿瘤的遗传改变作为分子预后因素。

• 发表时间: 2003
• 期刊: Neuropathology 23
• 作者: Shiraishi T;Tabuchi K
• 通讯作者: Tabuchi K

Induction of the DNA repair gene MGMT by dexamethasone in glioblastomas

地塞米松在胶质母细胞瘤中诱导 DNA 修复基因 MGMT

• 发表时间: 2004
• 期刊: Journal of Neurosurgery 101
• 作者: Okamoto H;Mineta T;Ueda S;Nakahara Y;Shiraishi T;Tamiya T;Tabuchi K;Okamoto H.;Shiraishi T;Ueda S
• 通讯作者: Ueda S