Targeting cannabinoid receptors in hepatocellular carcinoma?
Targeting cannabinoid receptors in hepatocellular carcinoma?
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DOI：
10.1136/gutjnl-2016-312108
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发表时间：
2016-06
期刊：
影响因子：
24.5
通讯作者：
A. Mallat;S. Lotersztajn
中科院分区：
文献类型：
--
作者：
A. Mallat;S. Lotersztajn
肝细胞癌（HCC）是一个主要的健康问题，占原发性肝癌的90%，也是全球癌症相关死亡的第二大原因。1该肿瘤主要发生在暴露于各种风险因素（包括B和C型肝炎病毒感染、过量饮酒和代谢综合征）后的肝硬化患者中。大多数患者被诊断为中期或晚期，不适合治愈性治疗。HCC的发生和发展与多种机制有关，包括慢性炎症、DNA损伤、表观遗传修饰、衰老、端粒酶再激活、染色体不稳定、新生血管形成等。然而，尽管对HCC生物学的理解有所进步，索拉非尼仍然是批准用于HCC治疗的单一药物，患者的总生存率略有改善。内源性大麻素包括两种典型的普遍存在的大麻素受体CB 1和CB 2的内源性配体家族，其中花生四烯酸酰胺（anandamide），一种由脂肪酸酰胺水解酶（FAAH）分解代谢的CB 1配体，和2-花生四烯酸甘油（2-arachydonoylglycerol），一种由单酰基甘油脂肪酶（MAGL）降解的CB 1/CB 2配体，是最好的特征。2这两种化合物也与非大麻素受体相互作用，瞬时受体电位（TRP）通道或G蛋白偶联受体55。内源性大麻素系统（ECS）已被确定为一个关键的调节...
Hepatocellular carcinoma (HCC) represents a major health problem, accounting for 90% of primary liver cancer and the second cause of cancer-related death worldwide.1 The tumour predominantly occurs in cirrhotic livers following exposure to various risk factors, including hepatitis B and C virus infection, excessive alcohol intake and metabolic syndrome. The majority of patients are diagnosed at intermediate or advanced stages and are ineligible for curative treatment. Several mechanisms contribute to the initiation and progression of HCC, including chronic inflammation, DNA damage, epigenetic modifications, senescence, telomerase reactivation, chromosomal instability, neo-angiogenesis. However, despite advances in the comprehension of HCC biology, sorafenib remains the single drug approved for HCC treatment with a marginal improvement of overall survival in patients. Endocannabinoids comprise a family of lipidic ligands for two canonical ubiquitous cannabinoid receptors, CB1 and CB2, among which anandamide, a CB1 ligand catabolised by fatty acid amide hydrolase (FAAH), and 2-arachydonoylglycerol, a CB1/CB2 ligand degraded by monoacylglycerol lipase (MAGL), are best characterised.2 Both compounds also interact with non-cannabinoid receptors, transient receptor potential (TRP) channels or G protein-coupled receptor 55. The endocannabinoid system (ECS) has been identified as a pivotal regulator …