Development of novel bio-therapy using hybrid peptide against intrahepatic cholangiocarcinoma

利用杂合肽开发抗肝内胆管癌的新型生物疗法

• 批准号: 23390318
• 负责人: ISHIGE Kazunori
• 金额: $ 12.15万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390318/
• 关键词: 胆道系悪性腫瘍; 分子標的治療; ハイブリッドペプチド; サイトカイン; 受容体

It is known that the interleukin-4 receptor alpha (IL-4R alpha) is highly expressed on the surface of various human solid tumors. We have newly designed IL-4R alpha-lytic hybrid peptide composed of binding peptide to IL-4R alpha and cell-lytic peptide. Here, we evaluated the antitumor activity of the IL-4R alpha-lytic hybrid peptide as a novel molecular targeted therapy in human biliary tract cancer (BTC) cells. IL-4R alpha-lytic hybrid peptide showed cytotoxic activity in siz BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5 micromoles/L. In addition, intravenous administration of IL-4R alpha-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R alpha-lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.

已知白细胞介素4受体α（IL-4Rα）在多种人类实体瘤表面高表达。我们新设计了 IL-4R α 裂解杂合肽，由 IL-4R α 结合肽和细胞裂解肽组成。在这里，我们评估了 IL-4R α-裂解杂合肽作为一种新型分子靶向疗法在人胆道癌 (BTC) 细胞中的抗肿瘤活性。 IL-4R α-裂解杂合肽在 siz BTC 细胞系中显示出细胞毒性活性，其浓度低至 5 微摩尔/L 即可杀死 5​​0% 的所有细胞 (IC50)。此外，静脉注射 IL-4R α-裂解杂合肽可显着抑制人 BTC 体内异种移植模型中的肿瘤生长。总而言之，这些结果表明 IL-4R α-裂解杂合肽是一种有效的药物，可能为 BTC 患者提供一种新的疗法。

项目成果

Lymphatic vessel endothelial hyaluronan receptor-1 is a novel prognostic indicator for human hepatocellular caecinoma

淋巴管内皮透明质酸受体-1是人肝细胞癌的新预后指标

• 发表时间: 2013
• 作者: Kitagawa K; Nakajima G; Kuramochi H; Ariizumi S; Y amamoto M
• 通讯作者: Y amamoto M

日本胆道学会認定指導医養成講座 胆石の種類と成因 第48回日本胆道学会学術集会記録

日本胆道学会认证讲师研修课程胆结石的种类及成因第48届日本胆道学会学术会议记录

• 发表时间: 2013
• 作者: 正田純一

Biliary tract carcinoma : clinical perspective on molecular targeting strategies for therapeutic options

胆道癌：治疗选择分子靶向策略的临床视角

• 发表时间: 2012
• 作者: Shoda J; Ishige K; Sugiyama H; Kawamoto; T
• 通讯作者: T

Orexin 2 receptioor as a potential target for the immunotoxin and antibody-drug conjugate cancer tgherapy

Orexin 2 受体作为免疫毒素和抗体-药物缀合物癌症治疗的潜在靶标

• 发表时间: 2012
• 影响因子: 2.9
• 作者: Kishida M; Ishige K; Horibe T; Tada N; Koibuchi N; Shoda J; Kita K; Kawakami K
• 通讯作者: Kawakami K

Amelioration of cisplatin-induced nephrotoxicity in Peroxiredoxin I-deficient mice

改善 Peroxiredoxin I 缺陷小鼠顺铂诱导的肾毒性

• 发表时间: 2012
• 作者: Okada K; Ma D; Warabi E; Morito N; Akiyama K; Yamagata K; Bukawa H; Shoda J; Ishii T; Yanagawa T
• 通讯作者: Yanagawa T