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应激和应激激素对非免疫原性同基因小鼠肿瘤移植性的影响。

The influence of stress and stress hormones on the transplantability of a non-immunogenic syngeneic murine tumor.

作者信息

Peters L J, Kelly H

出版信息

Cancer. 1977 Apr;39(4):1482-8. doi: 10.1002/1097-0142(197704)39:4<1482::aid-cncr2820390420>3.0.co;2-p.

Abstract

Quantitative transplantation assays of a syngeneic murine adenocarcinoma have been used to investigate the effects of stress hormones and tumor take probability. Cortisol, injected intraperitoneally one hour before and 3 hours after tumor cells, caused a dose dependent reduction of TD50 (number of tumor cells required for 50% takes) by factors of from 4 at a total dose 4 microng/g to 68 at 400 microng/g. ACTH, given at 0.2 I.U. daily for 9 days spanning the time of tumor cell injection, reduced the TD50 2.5-fold, indicating that the peak gluco-corticoid level achieved, rather than its duration, was of greater significance. Adrenaline, while much less effective than cortisol, produced an 8-fold reduction in TD50 at its maximum tolerable dose. The effect of cortisol simulated that of whole body irradiation (WBI), and while both these agents depress immune reactivity, evidence is presented to suggest that immunological mechanisms are not responsible for their effect. WBI constitutes a systemic stress, and the demonstration that surgical trauma (laparotomy) could also reduce the TD50 for this tumor suggested that both might act via endogenous glucocorticoids. However, the failure of prior total adrenalectomy of mice to abrogate the effect of either WBI or laparotomy indicated that stress hormones were not essential intermediaries. It is concluded that both stress hormones, especially glucocorticoids, and stressful procedures acting independently of stress hormones, can facilitate tumor transplantation.

摘要

同基因小鼠腺癌的定量移植试验已被用于研究应激激素和肿瘤接种成功率的影响。在肿瘤细胞接种前1小时和接种后3小时腹腔注射皮质醇,导致TD50(50%接种所需的肿瘤细胞数)呈剂量依赖性降低,总剂量为4微克/克时降低4倍,400微克/克时降低68倍。在肿瘤细胞注射期间的9天内,每天给予0.2国际单位促肾上腺皮质激素(ACTH),使TD50降低2.5倍,这表明所达到的糖皮质激素峰值水平而非其持续时间更具意义。肾上腺素虽然比皮质醇的效果差得多,但其最大耐受剂量时使TD50降低了8倍。皮质醇的作用模拟了全身照射(WBI)的作用,虽然这两种物质都会抑制免疫反应,但有证据表明免疫机制并非其作用原因。WBI构成一种全身性应激,而手术创伤(剖腹术)也能降低该肿瘤的TD50这一事实表明,两者可能都通过内源性糖皮质激素起作用。然而,事先对小鼠进行双侧肾上腺切除术未能消除WBI或剖腹术的作用,这表明应激激素并非必需的中间介质。结论是,应激激素,尤其是糖皮质激素,以及独立于应激激素起作用的应激程序,都能促进肿瘤移植。

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