TUMOR NECROSIS FACTOR
TUMOR NECROSIS FACTOR
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DOI：
10.1038/scientificamerican0588-59
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发表时间：
1988-05-01
影响因子：
3
通讯作者：
OLD, LJ
中科院分区：
文献类型：
--
作者：
OLD, LJ
这些事件，如果加以适当的艾德解释，是科学上许多进步的源泉。癌症的自然消退就是一个很好的例子。在世纪之交以前，一些精明的医生观察到病人体内恶性肿瘤的缩小有时与细菌感染的发展同时发生。他们假设感染因子或其产物可能以某种方式对抗癌症。这一概念以及后来支持它的数据，促使人们花了几十年的时间寻找一种可能导致从感染到癌症锡永的机制。一些证据表明，这种细菌并没有直接杀死肿瘤，而是加强了体内能够抑制癌症的力量的活动。为了实现这一想法，我和我的同事在纪念斯隆-凯特琳癌症中心大约15年前发现了一种小多肽，或蛋白质，它是由身体在细菌感染过程中产生的，可以杀死小鼠的肿瘤。我们和其他人现在正处于测试这种物质的早期阶段，我们将其命名为肿瘤坏死因子，作为人类的抗癌治疗。虽然该因子最初是因为其抗癌活性而被发现的，但进一步阐明其功能的努力表明，它也是炎症和免疫的中心调节剂，这些相互作用过程限制和修复损伤并对抗感染。它是所谓的细胞因子家族中的一员：将信号从一个细胞传递到另一个细胞的多肽介质。为了与其他物质结合，细胞因子构成炎症和免疫的分子语言，并形成一个复杂的相互作用和重叠的信号网络，协调身体的防御反应。这些强大的，有时由劳埃德]。旧的有毒蛋白质可以引发，增强或抑制彼此的影响。像肿瘤坏死因子一样，某些其他细胞因子，如干扰素（几种结构相关分子的通用术语），已知具有抗癌活性，并且也显示出作为癌症疗法的一些前景。对细胞因子的个体和组合效应的逐渐加深的理解也导致了对其他病症的治疗。例如，干扰素在人体试验中显示出对小鼠癌性肿瘤的出血性坏死作用，而这种作用在动物注射内毒素（革兰氏阴性菌的一种成分）后不久就发生了。尽管未经治疗的动物体内的癌症蓬勃发展（上图），但经治疗的动物体内的肿瘤会流血（因此呈黑色）并死亡（下图）。现在认为内毒素的这种作用不是直接的。相反，内毒素导致体内某些细胞分泌肿瘤坏死因子（TNF），然后作为肿瘤破坏剂。
Rre events, properly interpret ed, have been the source of much progress in science. The spontaneous regression of cancer is a case in point. Before the turn of the century a few astute physicians ob served that shrinkage of malignant tumors in patients sometimes coin cided with the development of bacte rial infections. They postulated that infectious agents or their products might somehow fight cancer. This notion, and the later data that supported it, prompted decades of search for a mechanism that could lead from infection to cancer regres sion. Some evidence suggested that the bacteria did not kill tumors di rectly but instead strengthened the activity of forces in the body that are capable of restraining cancer. In pur suit of this idea, my colleagues and I at the Memorial Sloan-Kettering Can cer Center some 15 years ago dis covered a small polypeptide, or pro tein, that is produced by the body in the course of bacterial infections and that kills tumors in mice. We and oth ers are now in the early stages of test ing the substance, which we named tumor necrosis factor, as an antican cer treatment for human beings. Although the factor was initially discovered because of its cancer-kill ing activity, efforts to elucidate its functions further have revealed that it is also a central regulator of in flammation and immunity, the inter twined processes that limit and re pair injuries and fight infection. It is one of a family of so-called cytokines: polypeptide mediators that transmit signals from one cell to another. To gether with other substances, cyto kines constitute the molecular lan guage of inflammation and immunity and form a complex interacting and overlapping network of signals that orchestrate the body's defensive re actions. These potent and sometimes by Lloyd]. Old toxic proteins can elicit, enhance or inhibit one another's effects. Like tumor necrosis factor, certain other cytokines, such as interferon (a general term for several structural ly related molecules), are known to have anticancer activity and are also showing some promise as cancer therapies. A gradually deepening un derstanding of the individual and combined effects of the cytokines is leading to treatments for other condi tions as well. For example, interferon has been shown in human trials toHEMORRHAGIC NECROSIS of a cancerous tumor in a mouse occurs soon after the ani mal is injected with endotoxin, a component of gram-negative bacteria. Whereas the cancer in an untreated animal thrives (top), the tumor in the treated animal bleeds into itself (hence the black color) and dies (bottom). It is now believed that this effect of en dotoxin is not a direct one. Instead the endotoxin causes certain cells in the body to secrete tumor necrosis factor (TN F), which then acts as an agent of tumor destruction.