Development of mTOR-targeted novel therapy inducing autophagy for B-cell lymphoma

开发 mTOR 靶向诱导 B 细胞淋巴瘤自噬的新疗法

• 批准号: 22591043
• 负责人: SATO Tsutomu
• 金额: $ 2.91万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591043/
• 关键词: リンパ腫; オートファジー; mTOR; 治療

Malignant lymphoma has been one of the hematological malignancies of which prognosis is still poor. The most possible reason of poor-prognosis is the resistance against conventional chemotherapeutic reagents, which are expected to induce apoptotic and/or necrotic death in lymphoma cells. Therefore, novel therapy with unique mechanism is required. Then, we have chosen the strategy inducing autolytic cell death, autophagy since the signaling of autophagic cell death does not depend on the apoptotic and necrotic signaling. For the induction of autophagy, we have used siRNA against mTOR. For the delivery of siRNA and the targeting of B-cell lymphoma, we have developed anti-CD19-targeted siRNA-PEG/KALA PECM system.

恶性淋巴瘤一直是预后较差的血液系统恶性肿瘤之一。预后不良的最可能的原因是对常规化疗试剂的抗性，其预期在淋巴瘤细胞中诱导凋亡和/或坏死性死亡。因此，需要具有独特机制的新疗法。然后，我们选择了诱导自溶细胞死亡的策略，自噬，因为自噬细胞死亡的信号传导不依赖于凋亡和坏死信号传导。为了诱导自噬，我们使用了针对mTOR的siRNA。针对siRNA的递送和B细胞淋巴瘤的靶向，我们开发了抗CD 19靶向的siRNA-PEG/KALA PECM系统。

项目成果

Successful Treatment by Fibrin Glue Sealant for Pneumothorax with Chronic GVHD Resistant to Autologous Blood Patch Pleurodesis

• DOI: 10.2169/internalmedicine.51.7355
• 发表时间: 2012-01-01
• 期刊: INTERNAL MEDICINE
• 影响因子: 1.2
• 作者: Iyama, Satoshi;Sato, Tsutomu;Kato, Junji
• 通讯作者: Kato, Junji

Novel missense mutation in the TMPRSS6 gene in a patient with iron-refractory iron deficiency anemia

铁难治性缺铁性贫血患者 TMPRSS6 基因的新错义突变

• 发表时间: 2011
• 作者: Kamihara Y;Sato T;et al
• 通讯作者: et al

Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis

• DOI: 10.1111/j.1872-034x.2011.00821.x
• 发表时间: 2011-07-01
• 期刊: HEPATOLOGY RESEARCH
• 影响因子: 4.2
• 作者: Sato, Tsutomu;Kobune, Masayoshi;Kato, Junji
• 通讯作者: Kato, Junji

A phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable biliary tract cancer

吉西他滨和 5-氟尿嘧啶动脉灌注化疗治疗不可切除胆道癌的 I 期试验

• 发表时间: 2011
• 期刊: Int J Clin Oncol
• 影响因子: 3.3
• 作者: Hayashi T;Kobune M;Takimoto R;Kato J
• 通讯作者: Kato J

Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia

• DOI: 10.1007/s12185-011-0881-0
• 发表时间: 2011-07-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Sato, Tsutomu;Iyama, Satoshi;Kato, Junji
• 通讯作者: Kato, Junji