Trosko James E, Tai Mei-Hui
Department of Pediatrics and Human Development, National Food Safety Toxicology Center, College of Human Medicine, Michigan State University, East Lansing, Mich., USA.
Contrib Microbiol. 2006;13:45-65. doi: 10.1159/000092965.
Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.
由微生物病原体、辐射、内源性或外源性化学物质诱导产生的炎症，已被证实与包括癌症在内的慢性疾病有关。由于癌症发生被描述为由“起始”“促癌”和“进展”阶段组成，炎症过程可能会影响其中任何一个阶段或所有三个阶段。癌症发生的干细胞理论得以复兴，因为已分离出人类成体干细胞，并证明它们是肿瘤转化的“靶点”。转录因子Oct4与成体干细胞及其永生化和致瘤衍生物有关，但与正常分化的子代无关。这些数据与癌症发生的干细胞理论一致。此外，间隙连接细胞间通讯（GJIC）似乎在细胞生长中起主要作用。非遗传毒性化学物质或各种癌基因对GJIC的抑制作用似乎是癌症发生的促癌和进展阶段的机制。许多毒素、合成非遗传毒性物质和内源性炎症因子已被证明可抑制GJIC并充当肿瘤促进剂。对GJIC的抑制可能是炎症过程影响癌症的机制，而在肿瘤促癌阶段用抗炎因子进行干预可能是最有效的抗癌策略。
