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目的为进一步了解肿瘤神经旁浸润(PNI)的概念、可能分子机制及临床意义,以寻找新的肿瘤治疗途径。方法对有关PNI的定义、分子机制及临床研究文献进行综述并分析。结果目前对于PNI被广泛接受的定义是肿瘤接近并包绕至少33%神经周径或者穿透三层神经鞘中的任意一层。PNI不仅仅是简单的扩散,更像是浸润和侵犯。目前主要有“低阻力通道”和“信号交互传递”两种学说用以解释其发生机制。近期的研究表明“信号交互传递”更能合理解释PNI的发生机制。而包括成纤维细胞在内的基质成分,在促进PNI发生的复杂信号通路中起着关键作用;神经营养素和轴突导向分子在PNI的进程中起调节作用。临床研究发现,PNI在头颈部肿瘤、胃癌、胰腺癌、结直肠癌、前列腺癌等恶性肿瘤中是判断预后的指标,阳性提示预后较差,5年存活率较低。结论PNI的发生机理极为复杂,关于其详细的机理仍无明确的定论,故继续这方面的研究将为揭开肿瘤PNI的机理提供理论基础,也可为肿瘤的治疗提供新的靶点。
Objective To further understand the concept of tumor parainternal infiltration (PNI), possible molecular mechanism and clinical significance, in order to find new ways of tumor treatment. Methods The definition of PNI, molecular mechanisms and clinical research literature review and analysis. Results Currently the most widely accepted definition of PNI is that the tumor approaches and wraps around at least 33% of the peripheral nerve diameter or penetrates any of the three layers of the nerve sheath. PNI is not just a simple proliferation, more like infiltration and violation. At present, there are two theories of “low resistance channel” and “signal transmission” to explain its mechanism. Recent research shows that “signal exchange ” more reasonable explanation of the mechanism of PNI. Matrix components, including fibroblasts, play a key role in complex signaling pathways that promote PNI. Neurotrophins and axon guidance molecules play a regulatory role in PNI progression. Clinical study found that PNI in the head and neck cancer, gastric cancer, pancreatic cancer, colorectal cancer, prostate cancer and other malignancies is to determine the prognosis of the indicators, positive prognosis is poor, 5-year survival rate is low. Conclusions The mechanism of occurrence of PNI is extremely complicated. There is still no definite conclusion about the detailed mechanism of PNI. Therefore, continuing the research in this aspect will provide a theoretical basis for revealing the mechanism of tumor PNI and may also provide a new target for the treatment of tumors.