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[细胞因子在癌症治疗中的作用]

[The role of cytokines in cancer therapy].

作者信息

Ishida N, Yoshida T

出版信息

Gan To Kagaku Ryoho. 1987 May;14(5 Pt 1):1187-93.

PMID:3034167
Abstract

A variety of normal tissue or malignant cells can produce and/or release various biologically active substances (hormone-like mediators) now collectively called cytokines. Because immunological and non-immunological responses of malignant cells were modified by many of them, some cytokines have been employed as so-called Biological Response Modifiers (BRM) in the treatment of cancers in animals and humans. This overview discussed a few of the difficulties, probably inherent in cytokine therapy, that have already been encountered in early clinical trials as well as some of those that can be anticipated in future work. These include unexpected and undesirable reactions due to the systemic administration in relatively large amounts of a cytokine that is, under physiological conditions, supposed to act as a paracrine and/or autocrine among cells located within a limited distance. Even a pure recombinant preparation of a cytokine is now known to affect multiple target cells if they are accessible to it. Furthermore, this kind of therapy may sometimes be little more than a shot in the dark, since the physiological balance (homeostasis) among many of the cytokines present or produced in a host receiving a large quantity of exogenous cytokines is not well understood. Making the situation still more complicated, many types of tumor cells are known to release some of these cytokines spontaneously. Many challenging problems remain to be solved before we can confidently prescribe a cocktail of cytokines precisely suitable for a given patient according to the individual's in vivo cytokine profile. Nevertheless, in spite of all these reservations, cytokine therapy has been too frequently beneficial to be allowed to be discouraged. "Out of this nettle, danger, we pluck this flower, safety".

摘要

多种正常组织或恶性细胞能够产生和/或释放各种生物活性物质(类激素介质),现在这些物质统称为细胞因子。由于其中许多物质会改变恶性细胞的免疫和非免疫反应,一些细胞因子已被用作所谓的生物反应调节剂(BRM),用于动物和人类癌症的治疗。本综述讨论了细胞因子治疗中可能固有的一些困难,这些困难在早期临床试验中已经遇到,以及未来工作中可能预期到的一些困难。这些困难包括,由于在生理条件下本应在有限距离内的细胞之间作为旁分泌和/或自分泌起作用的细胞因子以相对大量进行全身给药而产生的意外和不良反应。现在已知即使是细胞因子的纯重组制剂,如果多个靶细胞能够接触到它,也会对其产生影响。此外,这种治疗有时可能只不过是盲目尝试,因为在接受大量外源性细胞因子的宿主中,许多现有或产生的细胞因子之间的生理平衡(内环境稳态)尚未得到充分了解。更复杂的是,已知许多类型的肿瘤细胞会自发释放其中一些细胞因子。在我们能够根据个体的体内细胞因子谱自信地开出一种完全适合特定患者的细胞因子鸡尾酒之前,仍有许多具有挑战性的问题有待解决。然而,尽管有所有这些保留意见,细胞因子治疗已经带来了太多益处,不能因此而气馁。“从这危险的荨麻中,我们采得这朵安全之花”。

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