Proteomics analysis of a mechanism of sinusoidal endothelial cell injury after receiving oxaliplatin-based chemotherapy in colorectal liver metastases.

结直肠肝转移瘤接受奥沙利铂化疗后肝窦内皮细胞损伤机制的蛋白质组学分析。

• 批准号: 22591509
• 负责人: NAKANO Hiroshi
• 金额: $ 3万
• 依托单位: St. Marianna University School of Medicine
• 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-22591509/
• 关键词: 大腸癌肝転移術前化学療法; oxaliplatin-based chermotherapy; sinusoidal obstruction syndrome; プロテオミクス; glutathione S-transferase M1; sphingosine 1 phosphate; 大腸癌肝転移; 肝切除; 術前化学療法; 肝障害; Blue liver; Peroxiredoxin 6; 化学療法関連肝障害; ジヌソイド閉塞症候群; オキザリプラチン; Aldehyde

Oxaliplatin-based chemotherapy in patients with colorecatl liver metastases has been shown to be significantly associated with sinusoidal obstruction syndrome (SOS). In the present study, our proteomics study using 2-Dimensional electrophoresis and LC/MS/MS showed that Peroxiredoxin6、Aldehyde dehydrogenase 2、 α-methylacetyl-CoA racemase、Protein disulfide-isomerase A3、60-S-acid ribosomal protein P0、and Glutathione S-transferase M1 (GST-M1) significantly differed as compared with the control sinusoidal cells. Among them, GST-M1 significantly decreased in human sinusoidal endothelial cells after the administration of oxaliplatin. In addition, an administration of sphingosine 1 phosphate (S1P), which has a protective effect on sinusoidal endothelial injury, significantly attenuate the oxaliplatin-induced sinusoidal injury and showed the maintenance of GST-M1 concentration. These results suggests thatGST-M1 and S1P have a crucial role of oxaliplatin-induced sinusoidal endothelial inj.

在结肠癌肝转移患者中，以奥沙利铂为基础的化疗已被证明与窦阻塞综合征（SOS）显著相关。在本研究中，我们使用二维电泳和LC/MS/MS进行的蛋白质组学研究表明，过氧化物氧还蛋白6、醛脱氢酶2、α-甲基乙酰辅酶A消旋酶、蛋白二硫键异构酶A3、60-S-酸性核糖体蛋白P0和谷胱甘肽S-转移酶M1（GST-M1）与对照窦状细胞相比显着不同。其中，在给予奥沙利铂后，人肝窦内皮细胞中GST-M1显著降低。此外，鞘氨醇1磷酸（S1 P）的管理，这对窦内皮损伤具有保护作用，显着减弱奥沙利铂诱导的窦损伤，并显示GST-M1浓度的维持。提示GST-M1和S1 P在奥沙利铂诱导的肝窦内皮损伤中起重要作用。

项目成果

Comparative Study of Culture Conditions for Maintaining CYP3A4 and ATP-Binding Cassette Transporters Activity in Primary Cultured Human Hepatocytes.

原代培养人肝细胞中维持 CYP3A4 和 ATP 结合盒转运蛋白活性的培养条件的比较研究。

• 发表时间: 2011
• 期刊: Journal of Pharmacological Sciences. vol.115、No.4
• 作者: Yuko Takeba;Naoki Matsumoto;Sachiko Takenoshita-Nakaya;Yoshie Harimoto;Toshio Kumai;Yuichi Kinoshita;Hiroshi Nakano;Takehito Ohtsubo;Shinichi Kobayashi
• 通讯作者: Shinichi Kobayashi

進性・再発大腸癌の化学療法関連肝障害:脾容積、AST/血小板比、プロテオミクス解析によるchemotherapy-naive patientsの抽出

晚期/复发性结直肠癌化疗相关的肝损伤：通过脾脏体积、AST/血小板比和蛋白质组学分析识别未接受化疗的患者

• 发表时间: 2012
• 作者: 中野浩;他;中野浩
• 通讯作者: 中野浩

Splenomegaly in oxaliplatin-naive patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy in stage IV or recurrent colorectal cancer

IV 期或复发性结直肠癌化疗前天冬氨酸转氨酶与血小板的比率可以预测未接受奥沙利铂治疗的患者因化疗相关肝毒性而出现的脾肿大

• 发表时间: 2012
• 作者: 中野浩;他;中野浩;Iimuro Y;Nakano H
• 通讯作者: Nakano H

大腸癌肝転移に対する治療のUpdate:化学療法による肝組織障害

结直肠癌肝转移治疗进展：化疗引起的肝组织损伤

• 发表时间: 2010
• 期刊: 外科治療
• 作者: 中野浩;他
• 通讯作者: 他

Splenic Volume Increase due to Preoperative Chemotherapy may Impair Long-Term Outcome after Hepatectomy in Patients with Initially Non-Optimally Resectable Colorectal Cancer Liver Metastases.

对于最初不可最佳切除的结直肠癌肝转移患者，术前化疗导致的脾体积增加可能会损害肝切除术后的长期结果。

• 发表时间: 2013
• 期刊: Hepatogastroenterol
• 作者: Katayama M;Nakano H;et al.
• 通讯作者: et al.