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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.

目的和宗旨：内源性大麻素（CB）已被证实在炎症反应中起早期介质的作用，而高迁移率族蛋白-1（HMGB-1）被认为是炎症反应的晚期介质，可诱导多种生理作用。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肝癌发生发展的关系。患者和方法：采用高效液相色谱-质谱联用技术（LC/MS）测定45例肝细胞癌（HCC）、23例肝硬化（LC）、10例慢性肝炎（CH）患者和34例健康志愿者血清中CB、2-花生四烯酸甘油（2-AG）和花生四烯酸乙醇酰胺（AEA）的含量。采用酶联免疫吸附试验检测血清HMGB-1和6种炎性细胞因子水平（HV：n=10，CH：n=5，LC：n=7，HCC：n=17）。CB受体的表达。采用免疫组织化学方法对23例肝癌切除标本进行CBIR、CB 2 R以及晚期糖基化终产物受体（RAGE）检测。结果如下：肝癌患者血清2-AG水平为15.92 ± 7.30ng/ml，显著高于其他各组（P< 0.01）。血清IL-8水平在中晚期肝癌组明显升高（P< 0.01）。肝癌组HMGB-1平均水平为5.51± 2.92ng/ml，显著高于其他各组（P <0.01）。2-AG与HMGB-1呈显著相关（r=0.872，P< 0.01）。I-ICC免疫组化分析显示，CB 1 R和Bcl-2的表达与HCC的去分化有关。结论：2-AG、CBIR、IL-8和FIMGB-1可能与HCC的发生发展有关。阻断这些介质可能具有预防和治疗HCC的潜力。