Development of novel therapeutic strategy against tumor progression using animal model

使用动物模型开发针对肿瘤进展的新治疗策略

• 批准号: 21590432
• 负责人: KITAGAWA Masanobu
• 金额: $ 3万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590432/
• 关键词: 疾患モデル動物; レトロウイルス; DNA損傷; アポトーシス; p53; DNA-PK

The interaction of viral proteins with host-cellular proteins elicits the activation of cellular signal transduction pathways. Previously, we have clarified that an infection with Friend leukemia virus(FLV) markedly enhanced the IR-induced apoptosis of hematopoietic cells in C3H mice in association with P53, ATM, and DNA-PK. The phenomenon was characterized in vivo by severe anemia when the mice were infected with FLV and then treated with a low dose of total body irradiation(TBI). Viral infection and replication occurred almost cell type-specifically in the hematopoietic cells and thus, the apoptotic enhancement was observed only in the hematopoietic cells. However, p53 knockout mice, Atm knockout mice, and DNA-PK-deficient SCID mice with a C3H background did not exhibit this phenotype. A comparison of apoptotic signals after FLV, TBI, or FLV+TBI treatment of these mice revealed that ATM appeared to be necessary for the general signal transduction of TBI-induced apoptosis, while DNA-PK had a specific role in enhancing p53-dependent apoptosis under FLV infection. The host specificity of this phenomenon was caused by the up-regulated expression of Acinus and minichromosome maintenance(MCM) 2 in C3H mice. We also showed that C3H mouse-derived hematopoietic cells originally expressed higher levels of MCM2 than BALB/c cells and exhibited more frequent apoptosis after DNA-damage by doxorubicin when the cells expressed the Friend leukemia virus envelope protein gp70. Transduction and immunoprecipitation assays using various deletion mutants of

病毒蛋白与宿主细胞蛋白的相互作用激活了细胞信号转导途径。以前，我们已经阐明，与朋友白血病病毒（FLV）感染显着增强IR诱导的造血细胞凋亡在C3 H小鼠与P53，ATM和DNA-PK。这种现象的特点是在体内严重贫血时，小鼠感染FLV，然后用低剂量的全身照射（TBI）治疗。病毒感染和复制几乎发生在造血细胞中的细胞类型特异性，因此，仅在造血细胞中观察到凋亡增强。然而，p53敲除小鼠、Atm敲除小鼠和具有C3 H背景的DNA-PK缺陷型SCID小鼠未表现出这种表型。这些小鼠经FLV、TBI或FLV+TBI处理后的凋亡信号比较显示，ATM似乎是TBI诱导的凋亡的一般信号转导所必需的，而DNA-PK在FLV感染下增强p53依赖性凋亡中具有特定作用。这种现象的宿主特异性是由C3 H小鼠中Acinus和微小染色体维持（MCM）2的表达上调引起的。我们还表明，C3 H小鼠来源的造血细胞最初表达更高水平的MCM 2比BALB/c细胞，并表现出更频繁的细胞凋亡后，DNA损伤阿霉素时，细胞表达的朋友白血病病毒包膜蛋白gp 70。转导和免疫沉淀试验使用的各种缺失突变体的

项目成果

プレB細胞性リンパ性白血病発症におけるC/ebpβとBLNK/IL-7 シグナルの協調作用について

C/ebpβ 和 BLNK/IL-7 信号在前 B 淋巴细胞白血病发展中的协同作用

• 发表时间: 2011
• 作者: Yuichi Murakami;Kosuke Watari;Tomohiro Shibata;Hiroki Ureshino;Akihiko Kawahara;Masayoshi Kage;Hiroto Izumi;Michihiko Kuwano;Mayumi Ono.;倉田盛人;NiuDongfengら;Ueha S;倉田盛人;12. 河原明彦，原田博史，多比良朋希，山口知彦，安部秀幸，吉田友子，髙瀨頼妃呼，福満千容，秋葉 純，鹿毛政義．;望月邦夫ら;倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎
• 通讯作者: 倉田盛人,北川昌伸,後飯塚僚,北村大介,中村卓郎

DNA損傷アポトーシス増強による癌治療動物モデル.

癌症治疗动物模型通过DNA损伤增强细胞凋亡。

• 发表时间: 2011
• 作者: 北川昌伸;倉田盛人;阿部晋也;鈴木志保;梅田茂明;菅原江美子;大西威一郎
• 通讯作者: 大西威一郎

血液発症におけるERストレス蛋白Xbp-1の機能

ER应激蛋白Xbp-1在血液发病机制中的作用

• 发表时间: 2009
• 作者: 倉田盛人;北川昌伸;中村卓郎
• 通讯作者: 中村卓郎

Giant cell carcinoma causing rapidly progressive respiratory failure as the presenting feature of acquired immunodeficiency syndrome

巨细胞癌导致快速进行性呼吸衰竭，这是获得性免疫缺陷综合征的表现特征

• 发表时间: 2010
• 期刊: Int J STD AIDS
• 影响因子: 1.4
• 作者: Sugawara E;Yamamoto K;Umeda S;Suzuki S;KurataM;Endo Y;Uchibori K;Akashi T;Inase N;Kitagawa M
• 通讯作者: Kitagawa M

骨髄異形成症候群における造血幹細胞因子の発現検討

骨髓增生异常综合征造血干细胞因子表达检测

• 发表时间: 2011
• 作者: 梅田茂明;山本浩平;倉田盛人;鈴木志保;菅原江美子;阿部晋也;小嶋洋輔;村山寿彦;北川昌伸
• 通讯作者: 北川昌伸