Modification of endoplasmic reticulum stress expands surgical indication in hepatocellular carcinom a

内质网应激的改变扩大了肝细胞癌的手术指征

• 批准号: 20591609
• 负责人: HATANO Etsuro
• 金额: $ 3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591609/
• 关键词: 癌; ストレス; アポトーシス; 肝細胞癌; 小胞体ストレス; CHOP; GADD153; JNK

C/EBP homologous protein (CHOP) is one of the key components of the endoplasmic reticulum (ER) stress-mediated apoptosis. We investigated the role of CHOP in cholestatic liver injury. Liver fibrosis was attenuated in CHOP knockout mice after bile duct ligation (BDL). Both apoptotic and necrotic hepatocyte deaths were attenuated in CHOP deficient mice. Cholestasis induces CHOP -mediated ER stress and t riggers hepatocyte death. CHOP deficiency attenuates hepatocyte death and subsequent liver fibrosis. CHOP expression was enhanced in human liver cirrhosis and hepatocellular carcinoma. Furthermore, inhibition of c-Jun NH_2-terminal kinase switches Smad3 signaling from oncogenesis to tumor-suppression in rat hepatocellular carcinoma. Taken together, we expect that modification of ER stress expands surgical indication in hepatocellular carcinoma.

C/EBP同源蛋白(CHOP)是内质网(ER)应激诱导的细胞凋亡的关键成分之一。我们研究了CHOP在胆汁淤积性肝损伤中的作用。CHOP基因敲除小鼠胆管结扎(BDL)后肝纤维化减轻。CHOP缺陷小鼠肝细胞的凋亡性和坏死性死亡均有所减轻。胆汁淤积诱导CHOP介导的内质网应激，触发肝细胞死亡。CHOP缺乏可减轻肝细胞死亡和随后的肝纤维化。CHOP在人肝硬变和肝细胞癌中的表达增强。此外，在大鼠肝细胞癌中，抑制c-jun氨基末端激酶将Smad3信号从致癌切换到肿瘤抑制。综上所述，我们期待ER应激的改变扩大了肝细胞癌的手术适应证。

项目成果

Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver

Dai-kenchu-to 通过抑制肝脏中中性粒细胞的积累来减轻大鼠肝窦阻塞综合征

• 发表时间: 2009
• 期刊: J Gastoroen Hepatol, 24
• 作者: Narita M.;Hatano;E.;Tamaki;N.;et al.
• 通讯作者: et al.

CHOP-deficiency attenuates cholestasis-induced liver fibrosis by redcution of hepatocyte injury.

CHOP 缺乏可通过减少肝细胞损伤来减轻胆汁淤积引起的肝纤维化。

• 发表时间: 2008
• 期刊: Am J Physiol 294(2)
• 作者: Tamaki;N.;Hatano;E.;Taura;K.;Tada;M.;Kodama Y.;Nitta;T.;Iwaisako;K.;Seo;S.;Nakajima;A.;Ikai;I.;Uemoto;S.
• 通讯作者: S.

JNKの肝発癌過程における分子標的意義- JNK阻害剤による肝細胞癌治療の可能性-

JNK分子靶向在肝癌发生过程中的意义 - JNK抑制剂治疗肝细胞癌的可能性 -

• 发表时间: 2009
• 作者: 長田博光;波多野悦朗;阿世知弘行;成田匡大;柳田敦子;玉置信行;猪飼伊和夫;松崎恒一;上本伸二
• 通讯作者: 上本伸二

Inhibition of c-Jun NH2-Terminal Kinase Switches Smad3 Signaling from Oncogenesis to Tumor-Suppression in Rat Hepatocellular Carcinoma

• DOI: 10.1002/hep.22860
• 发表时间: 2009-06-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Nagata, Hiromitsu;Hatano, Etsuro;Uemoto, Shinji
• 通讯作者: Uemoto, Shinji

Olprinone Attenuates Excessive Shear Stress Through Up-Regulation of Endothelial Nitric Oxide Synthase in a Rat Excessive Hepatectomy Model

• DOI: 10.1002/lt.22189
• 发表时间: 2011-01-01
• 期刊: LIVER TRANSPLANTATION
• 影响因子: 4.6
• 作者: Yamanaka, Kenya;Hatano, Etsuro;Uemoto, Shinji
• 通讯作者: Uemoto, Shinji