癌转移研究的几个重要问题

Important issues of cancer metastasis

40年来小肝癌切除患者5年生存率没有提高的原因是肿瘤的转移复发，提示研究癌转移的重要性。由此简单论述癌转移研究的几个问题。（1）癌转移观念的更新：癌转移是全身性问题，癌转移潜能起源于原发肿瘤，肿瘤干细胞是癌转移的关键，癌转移还受免疫炎症微环境的影响，癌转移潜能可双向改变。（2）杀癌疗法促进残癌转移：复旦大学附属中山医院肝癌研究所采用高转移潜能人肝癌裸鼠模型做实验研究，发现姑息性切除、放疗、化疗、肝动脉结扎以及针对VEGF的分子靶向治疗（如索拉非尼）均可通过乏氧、炎症、免疫抑制等促进残癌转移。而临床一些常用药物可抑制其促转移作用并延长动物生存时间，如细胞因子中的干扰素，抗炎剂中的阿司匹林和唑来膦酸，中药小复方“松友饮”和丹参酮ⅡA，酪斯亮肽。（3）全身性干预：包括神经系统干预、免疫治疗、内分泌干预和代谢干预等。

The 5-year survival rates of small liver cancer resection were no longer improved in the past 40 years, indicating the importance of studies on cancer metastasis. Sever- al important issues of cancer metastasis will be delineated ： （ 1 ） Changing concepts of cancer metastasis： Cancer metastasis is a systemic issue, metastatic potential of cancer originated from pri- mary tumor, cancer stem cell is the key component of cancer metastasis, metastatic potential also influenced by immune- inflammatory microenvironment, metastatic potential is an alterable event. （2） The pro-metastatic effect of cancer eradication： In Liver Cancer Institute of Fudan University, experimental studies using human hepatocellular carcinoma nude mice model with high metastatic potential indicated that palliative resection, radiotherapy, chemotherapy, hepatic artery ligation and molecular targeted therapies that target to VEGF （eg. Sorafenib） promoted the metastatic potential of residual cancer, mainly via hypoxia, inflammation and immuno-suppression with different molecular alterations. Interestingly, effective intervention that inhibits metastasis and prolongs survival has been found using clinical available drugs in experimental studies. Such as cytokine （inter-feron）, anti-inflammatories （aspirin and zoledronie acid）, herbal medicine （Songyou Yin） and Tanshinone Ⅱ A, a novel tripeptide-tyroserleutide, etc. （3） Systemic intervention, inclu- ding nervous system, immunotherapy, endocrinal intervention, as well as metabolic intervention, etc. were briefly discussed.