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首页> 外文期刊>British Journal of Cancer >Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA
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Similarities of the Anti-tumour Actions of Endotoxin, Lipid A and Double-stranded RNA

机译：内毒素，脂质A和双链RNA的抗肿瘤作用的相似性

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Double stranded RNA (dsRNA) whether isolated from a fungal virus or prepared synthetically (i.e., Poly I Poly C) and endotoxin were found to exert very similar effects on syngeneic murine lymphomata and fibrosarcomata. They cause complete regressions of some established subcutaneous (s.c.) or intradermal (i.d.) tumours but not of intraperitoneal (i.p.) tumours when administered either systemically or directly into the tumour. To achieve this effect the tumours must be fully established and the best results were obtained when treatment was started 7 days after transplant. If treatment is started within the first 3 days following the transplantation of the tumour then only a slight inhibition of growth rate was observed. These agents can also act prophylactically and protect mice against a subsequent challenge but only if this is given i.p. and not if given s.c. or i.d. The prophylactic action is explained by the action of dsRNA and endotoxin on peritoneal macrophages which cause them to become cytotoxic to tumour cells (i.e., to become activated).The therapeutic effect of systemically administered endotoxin and dsRNA on established tumours is not the result of a direct action on the tumour cells themselves but is a complex process requiring the co-operation of several host factors. Haemorrhagic necrosis involving coagulation is essential (i.e., heparinization reduces the regression of tumours) but is not itself sufficient. Immunosuppression by whole body irradiation or by antilymphocyte serum also interferes with the antitumour action of dsRNA and endotoxin in spite of the fact that haemorrhagic necrosis still occurs. Also, the magnitude of the antitumour action correlated in a series of different tumours with their antigenicity. The observed tumour regressions are probably brought about by (1) vascular damage in the tumour which permits immune defence mechanisms of the host to gain access to the tumour and (2) activation of macrophages present within the tumour. The relative contribution of these two mechanisms may depend on the nature of the tumour and the route of administration of the active agents.Dibenyline, which protects against the lethal action of endotoxin by preventing the action of the catecholamines on the α-adrenergic receptors, makes it possible to increase the effectiveness of endotoxin in tumours by allowing a large dose to be given. Lipid A, a derivative of endotoxin which does not contain polysaccharide, has similar antitumour action to dsRNA and endotoxin. Some common features of the chemical structure of lipid A and dsRNA are discussed.
机译：发现从真菌病毒中分离或合成制备的双链RNA（dsRNA）（即Poly I Poly C）和内毒素对同源小鼠淋巴瘤和纤维肉瘤具有非常相似的作用。当全身或直接施用于肿瘤时，它们会导致某些已确立的皮下（s.c.）或皮内（i.d.）肿瘤的完全消退，而不会导致腹膜内（i.p.）肿瘤的消退。为了达到这种效果，必须在移植后7天开始完全治疗肿瘤并获得最佳结果。如果在肿瘤移植后的前三天内开始治疗，则仅观察到生长速率的轻微抑制。这些试剂还可以预防性地发挥作用，并保护小鼠免受随后的攻击，但前提是腹腔注射。而不是s.c.或dsRNA和内毒素对腹膜巨噬细胞的作用解释了其预防作用，这些作用使它们对肿瘤细胞具有细胞毒性（即被激活）。全身施用内毒素和dsRNA对已确诊的肿瘤的治疗作用并非是直接作用于肿瘤细胞本身，但这是一个复杂的过程，需要多种宿主因子的配合。涉及凝血的出血性坏死是必不可少的（即，肝素化可减少肿瘤的消退），但其本身并不足够。尽管仍然存在出血性坏死，但通过全身照射或抗淋巴细胞血清进行的免疫抑制也干扰dsRNA和内毒素的抗肿瘤作用。同样，在一系列不同的肿瘤中，抗肿瘤作用的强度与其抗原性相关。所观察到的肿瘤消退可能是由（1）肿瘤中的血管损伤引起的，该损伤允许宿主的免疫防御机制进入肿瘤，以及（2）激活肿瘤内存在的巨噬细胞。这两种机制的相对作用可能取决于肿瘤的性质和活性剂的给药途径。地贝尼林通过阻止儿茶酚胺对α-肾上腺素能受体的作用来防止内毒素的致死作用。通过给予大剂量可以增加内毒素在肿瘤中的效力。脂质A是不含多糖的内毒素衍生物，与dsRNA和内毒素具有相似的抗肿瘤作用。讨论了脂质A和dsRNA的化学结构的一些共同特征。

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