The Role of Inflammation in Liver Cancer
The Role of Inflammation in Liver Cancer
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DOI：
10.1007/978-3-0348-0837-8_16
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Bishayee, Anupam
中科院分区：
文献类型：
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作者：
Bishayee, Anupam
已知持续性炎症可促进和加重恶性肿瘤。原发性肝癌，主要是肝细胞癌（HCC），是炎症相关癌症的明显例子，因为超过90%的HCC在肝损伤和炎症的背景下出现。HCC是世界范围内第五大常见恶性肿瘤和第三大癌症相关死亡原因，每年诊断出约100万新发病例，死亡人数几乎相等。慢性未解决的炎症与持续性肝损伤和并发再生相关，导致纤维化、肝硬化和最终HCC的顺序发展。不管各种病因因素之间的内在差异如何，HCC起源的共同点是由实质细胞死亡和由此产生的炎症级联激活的伤口愈合反应的持续存在。因此，识别导致从慢性肝损伤到异型增生和HCC转变的基本炎症信号传导途径可以描绘新的预测生物标志物和靶标，以识别和治疗慢性肝脏炎症患者。本章批判性地讨论了几个主要的细胞因子，趋化因子，生长因子，转录因子和酶的作用，以及一个独特的网络炎症信号通路的发展和HCC的进展。它还强调和分析了临床前动物研究，显示了通过各种天然化合物和合成药物靶向炎症介质和信号传导的创新方法，以实现有效的治疗以及预防肝脏恶性肿瘤。此外，目前的局限性和潜在的挑战与炎症信号的抑制，以及未来的研究方向，以加快临床开发的抗炎药，以预防和治疗肝癌。
Persistent inflammation is known to promote and exacerbate malignancy. Primary liver cancer, mostly hepatocellular carcinoma (HCC), is a clear example of inflammation-related cancer as more than 90 % of HCCs arise in the context of hepatic injury and inflammation. HCC represents the fifth most common malignancy and the third leading cause of cancer-related death worldwide with about one million new cases diagnosed every year with almost an equal number of deaths. Chronic unresolved inflammation is associated with persistent hepatic injury and concurrent regeneration, leading to sequential development of fibrosis, cirrhosis, and eventually HCC. Irrespective of the intrinsic differences among various etiological factors, a common denominator at the origin of HCC is the perpetuation of a wound-healing response activated by parenchymal cell death and the resulting inflammatory cascade. Hence, the identification of fundamental inflammatory signaling pathways causing transition from chronic liver injury to dysplasia and HCC could depict new predictive biomarkers and targets to identify and treat patients with chronic liver inflammation. This chapter critically discusses the roles of several major cytokines, chemokines, growth factors, transcription factors, and enzymes as well as a distinct network of inflammatory signaling pathways in the development and progression of HCC. It also highlights and analyzes preclinical animal studies showing innovative approaches of targeting inflammatory mediators and signaling by a variety of natural compounds and synthetic agents to achieve effective therapy as well as prevention of hepatic malignancy. Additionally, current limitations and potential challenges associated with the inhibition of inflammatory signaling as well as future directions of research to accelerate clinical development of anti-inflammatory agents to prevent and treat liver cancer are presented.