Department of Biomedical Sciences and Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter St., Amarillo, TX 79106, USA.
Biomolecules. 2017 Mar 27;7(2):34. doi: 10.3390/biom7020034.
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers. The roles of reactive astrocytes, tumor associated microglia and macrophages, metabolic alterations, microsatellite instability, ⁶-methylguanine DNA methyltransferase (MGMT) DNA repair and epigenetic alterations mediated by the isocitrate dehydrogenase 1 (IDH1) mutations have been discussed. The inflammatory pathways with relevance to the brain cancer treatments have been highlighted.
中枢神经系统肿瘤包括原发性癌症和脑转移瘤,仍然是最致命的肿瘤,治疗极具挑战性。大量证据表明,炎症在导致神经胶质瘤发生、恶性进展和中枢神经系统(CNS)微环境中肿瘤侵袭性的病理学中起着至关重要的作用。这篇综述总结了氧化应激、白细胞介素、肿瘤坏死因子-α(TNF-α)、环氧化酶以及转录因子如信号转导和转录激活因子 3(STAT3)和核因子 kappa-轻链增强子的激活 B 细胞(NF-κB)以及相关的串扰对 CNS 癌症炎症信号的重要贡献。还讨论了反应性星形胶质细胞、肿瘤相关的小胶质细胞和巨噬细胞、代谢改变、微卫星不稳定性、6-甲基鸟嘌呤 DNA 甲基转移酶(MGMT)DNA 修复以及异柠檬酸脱氢酶 1(IDH1)突变介导的表观遗传改变的作用。强调了与脑癌治疗相关的炎症途径。