Significance of inflammatory mediators in hepatocellular carcinoma

炎症介质在肝细胞癌中的意义

基本信息

批准号：
18591525
负责人：
ISHII Yuji
金额：
$ 2.53万
依托单位：
Jikei 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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Aim and Purpose : Endogenous cannabinoids (CBs) have been confirmed to play a role as early mediators, while high mobility group box-1 (HMGB-1) is known to be a late mediator in inflammatory response with inducing various physiologic actions. The aim of this study is to clarify a relationship between various inflammatory mediators including cytokines for the development and progression of HCC. Patients and Methods : For patients with hepatocellular carcinoma (HCC:n=45), liver cirrhosis (LC:n=23) or chronic hepatitis (CH:n=10) as well as in healthy volunteers (HV, n=34), the serum levels of CBs, 2-arachidonoylglycerol (2-AG) and anandamide (AEA) were measured by high performance liquid chromatography combined mass spectrometry (LC/MS). The serum levels of HMGB-1 and 6 inflammatory cytokines were measured by an enzyme-linked immunosorbent assay (HV:n=10, CH:n=5, LC:n=7, HCC:n=17). The expression of receptors for CBs. CBIR and CB2R as well as receptor for advanced glycation end product (RAGE) were examined by immunohistochemical analyses using the resected samples of HCC (n=23). Results : In patients with HCC, the mean level of 2-AG was 15.92 ± 7.30 ng/ml, which was significantly higher than those of the other groups (p< 0.01). The serum level of IL-8 was significantly higher in the advanced HCC group (p< 0.01). The mean level of HMGB-1 in HCC group was 5.51±2.92 ng/ml, which was significantly higher than those of the other groups (p <0.01). There existed a significant correlation between 2-AG and HMGB-1 (r=0.872, P< 0.01). In the immunohistochemical analysis of I-ICC, the expressions of CB1R and RAGE correlated with dedifferentiation of HCC. Conclusions : 2-AG, CBIR, IL-8 and FIMGB-1 seem to be associated with the development and progression of HCC. Blockade of such mediators may have potential for prevention and treatment of HCC.

目的和目的：内源性大麻素（CB）已被证实发挥着早期介质的作用，而高迁移率族盒-1（HMGB-1）已知是晚期炎症反应的介质，可诱导各种生理作用。本研究的目的是阐明包括细胞因子在内的各种炎症介质与 HCC 发生和进展的关系。患者和方法：对于肝细胞癌 (HCC:n=45)、肝硬化患者。 (LC:n=23) 或慢性肝炎 (CH:n=10) 以及健康志愿者 (HV, n=34) 中 CB、2-花生四烯酰甘油 (2-AG) 和花生四烯酸乙醇胺 (AEA) 的血清水平采用高效液相色谱联合质谱法（LC/MS）测定血清中HMGB-1和6炎症细胞因子的水平，采用酶联免疫吸附测定法测定血清中HMGB-1和6炎症细胞因子的含量。 (HV：n＝10，CH：n＝5，LC：n＝7，HCC：n＝17)检查CBIR和CB2R受体以及晚期糖基化终末产物(RAGE)受体的表达。使用 HCC 切除样本进行免疫组织化学分析 (n=23) 结果：HCC 患者中 2-AG 的平均水平为 15.92 ± 7.30。 ng/ml，显着高于其他组（p < 0.01）。晚期 HCC 组血清中 HMGB-1 的平均水平显着升高（p < 0.01）。 2-AG 组为 5.51±2.92 ng/ml，显着高于其他组（p <0.01）。2-AG 与 HMGB-1 之间存在显着相关性。 (r=0.872，P<0.01) I-ICC免疫组化分析中，CB1R和RAGE的表达与HCC去分化相关。结论：2-AG、CBIR、IL-8和FIMGB-1似乎相关。随着 HCC 的发生和进展，阻断此类介质可能具有预防和治疗 HCC 的潜力。