有关HAMLET治疗肿瘤疾病4篇重要文献部分翻译稿.doc

Apoptosis induced by a human milk protein 人乳蛋白诱导细胞凋亡 Proc. Natl. Acad. Sci. USA Vol. 92, pp. 8064-8068, August 1995 ABSTRACT To the breast-fed infant, human milk is more than a source of nutrients; it furnishes a wide array of molecules that restrict microbes, such as antibodies, bactericidins, and inhibitors of bacterial adherence. However, it has rarely been considered that human milk may also contain substances bioactive toward host cells. While investigating the effect of human milk on bacterial adherence to a human lung cancer cell line, we were surprised to discover that the milk killed the cells. Analysis of this effect revealed that a component of milk in a particular physical state-multimeric a-lactalbumin- is a potent Ca2+-elevating and apoptosis-inducing agent with broad, yet selective, cytotoxic activity. Multimeric a-lactalbumin killed all transformed, embryonic, and lymnphoid cells tested but spared mature epithelial elements. These findings raise the possibility that milk contributes to mucosal immunity not only by furnishing antimicrobial molecules but also by policing the function of lymphocytes and epithelium. Finally, analysis of the mechanism by which multimeric a-lactalbumin induces apoptosis in transformed epithelial cells could lead to the design of antitumor agents.对母乳喂养婴儿来说，母乳不仅是营养来源，而且也提供着丰富的分子用以抵御微生物体，如抗体和细菌素，并限制细菌粘附。然而，人们很少想到母乳中也会含有针对宿主细胞的生物活性物质。在调查母乳对细菌粘附到人肺癌细胞株的影响时，我们惊奇地发现母乳杀死了癌细胞。对此结果做进一步分析后得出是母乳中的一种成分，以α-乳白蛋白多聚体形式存在，能够提高钙离子浓度，作为细胞凋亡的诱导剂；并有选择性地发挥对细胞的毒性。α-乳白蛋白多聚体能杀灭所有转化、胚胎和淋巴样细胞，但对成熟的上皮细胞无作用。这些发现提醒我们：母乳有助于粘膜免疫系统不仅是因为产生了抗菌分子，而且也在于policing the function of lymphocytes and epithelium。最后，分析α-乳白蛋白多聚体能在分化的上皮细胞中诱导肿瘤细胞凋亡的机理能为我们设计抗肿瘤药提供思路。 以下仅将最有参考价值的图表列示，其余部分可见原文。 表1 人乳和人乳中各组分对人肺癌细胞株A549存活率的影响（这是体外细胞实验） 表中细胞存活率下“TBE”和“TI”列分别为2种不同的染色法下活细胞计数结果 图1 MDCK（一种肾癌细胞株）暴露于人乳中产生的凋亡（人乳1:10稀释，24小时）A 对照样 B 实验样  HAMLET Kills Tumor Cells by Apoptosis: Structure, Cellular Mechanisms, and Therapy HAMLET通过诱发凋亡杀灭肿瘤细胞：结构，细胞机制和疗效 J. Nutr. 135: 1299–1303, 2005. ABS