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作者 : sofina 原文出处 1 Cao GW. Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis. Hepatoma Res 2017;3:241-59. DOI:10.20517/2394-5079.2017.45 摘要 2 感染，污染和代谢兴奋剂及其与免疫遗传倾向的相互作用可能导致的非可控炎症为癌症发展提供了一个肥沃的土壤。在肝细胞癌中，这种特征是非常明显的。在这里，作者基于乙肝病毒诱导的肝癌发生发展提出了称为癌症进化发育学这一新假说的框架。这个理论的核心方面如下：（1）由免疫遗传性和乙型肝炎病毒感染相互作用引起的免疫失衡所导致的不可控性炎症；（2）活性炎症执行者通过失衡突变力（包括胞苷脱氨酶）和突变修复力（包括尿嘧啶-DNA糖基酶），促进病毒和宿主基因组中的突变，从而促进癌症相关的体细胞突变和病毒突变；（3）体细胞突变改变生存信号的一小部分细胞适应炎症微环境，通过胞苷脱氨酶的脱甲基作用去分化，并逆向发展成肿瘤起始细胞；（4）在来自肿瘤浸润成纤维细胞和M2巨噬细胞的一些因子如POSTN的培养下，TIC获得干细胞特性，癌细胞在不同微环境的选择压力下获得明显的转移和耐药潜力。（5）氧气存在下的糖酵解持续性为细胞存活提供了必需的能量，并为DNA合成提供了原料。因此，癌症发展的特征是“突变-选择-适应”。癌症进化发育学的框架可以在其他癌症中进行验证。该理论为理解炎症促进癌症发展的机制奠定了理论基础，同时它也在癌症的具体预防，预测和靶向治疗中起到积极作用。 关键词：炎症，乙肝病毒，突变，肝癌，癌症进化发育 Non-resolving inflammation, which may be maintained by infection, pollution, and metabolic stimulants and their interactions with immunogenetic predisposition, provides a fertile field for cancer development. This is strongly evident in hepatocellular carcinoma. Here, the framework of a hypothesis called Cancer Evo-Dev is presented, based on the advances in hepatitis B virus-induced hepatocarcinogenesis. Several aspects central to this theory are as follows: (1) immune imbalance caused by the interaction of immunogenetic predispositions and hepatitis B virus infection maintains non-resolving inflammation; (2) active inflammation executants promote mutations in viral and host genomes via disbalancing mutagenic forces including cytidine deaminases and mutation-repairing forces including uracil-DNA glycosylases, thus promoting cancer-related somatic mutations and viral mutations; (3) a small percentage of the cells whose somatic mutations alter the survival signalling adapt to the inflammatory microenvironment, de-differentiate via demethylating role of cytidine deaminases, and reversely develop into tumor-initiating cells (TICs); (4) under the cultivation of some factors like POSTN from tumor-infiltrating fibroblasts and M2 macrophages, TICs acquire the stemness, cancer-stem cells obtain distinct metastatic and drug-resistant potentials under the selection pressure from distinct microenvironments; (5) glycolysis persistence in the presence of oxygen provides essential energy for cell survival and the raw material for DNA synthesis. Thus, cancer development is characterized by an evolutionary process of “mutation-selection-adaptation”. The framework of Cancer Evo-Dev can be verified in other cancers. Cancer Evo-Dev lays theoretical foundation for understanding the mechanisms by which inflammation promotes cancer development, and it also plays a role in specific prophylaxis, prediction, and targeted treatment of cancers. Keywords: Inflammation, hepatitis B virus, mutations, hepatoma, Cancer Evo-Dev 原文链接 3 各位读者可复制此链接到浏览器中打开。 www.hrjournal.net/article/view/2267 |
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