Bassukas I D, Hofmockel G, Maurer-Schultze B
Institute of Medical Radiation Research, University of Würzburg, Germany.
Anticancer Res. 1994 Jan-Feb;14(1A):237-45.
Unfortunately the efficacy of the treatment of the metastatic or recurrent renal cell carcinoma (RCC) has not improved during the last few years. Recently effort has been put into the experimental and clinical evaluation of so-called "biological response modifiers" (BRM; cytokines and related peptides) as treatment modalities for RCC. The present results are, however, still disappointing. Since BRM, if applied alone, are largely ineffective as antineoplastic agents, more experimental studies are now necessary to test the antineoplastic value of their combinations, which seem to be more promising. In the present study, the in vivo effect of tumor necrosis factor a (TNF a) and/or interferon a (IFN a) on the macroscopic tumor growth (external caliper measurements of tumor size) and on the cell proliferation (in vivo 3H-thymidine labelling index, LI, and mitotic index, MI) of a human RCC xenograft line in nude mice has been investigated. Neither of these substances alone nor their combination was effective in changing the time course of the tumor sizes and the growth patterns of the treated tumors in a statistically significant manner as compared to the untreated controls. Also the cell kinetic parameters were only marginally affected by these treatments, whereby TNF a alone proved to be more effective than IFN a alone. However, compared to the effect of TNF alpha alone, the combination with IFN alpha leads to some amelioration of the cell kinetic perturbations and also to an appreciable shift in the growth patterns of the tumors from distinct Gompertzian (under TNF alpha alone) to near exponential (under the combination treatment; p < 0.05). As a consequence, the tumors grow more slowly under the combined treatment during the observation time, and on the other hand, their growth does not decelerate as much as under TNF alpha alone. Actually, if tumor growth continues in the same way, the extrapolation of the present data predicts smaller and greater tumors than the control tumors in the TNF alpha and in the combination treatment groups respectively. Notably, in the combination the effect of the IFN alpha seems to predominate. This is also seen in the effect of this combination on the cachexia of these tumor-bearing animals: either alone or in combination with TNF alpha, IFN alpha partially protects the animals from tumor-growth associated weight loss. Although the direct antineoplastic in vivo effect of the present cytokine combination against this human RCC xenograft line is rather limited, the potential antagonizing effect of IFN alpha on the development of cachexia should be further explored.
不幸的是，在过去几年中，转移性或复发性肾细胞癌（RCC）的治疗效果并未得到改善。最近，人们致力于对所谓的“生物反应调节剂”（BRM；细胞因子及相关肽）作为RCC治疗方式进行实验和临床评估。然而，目前的结果仍然令人失望。由于单独应用BRM作为抗肿瘤药物大多无效，现在需要更多的实验研究来测试它们联合应用的抗肿瘤价值，联合应用似乎更有前景。在本研究中，研究了肿瘤坏死因子α（TNFα）和/或干扰素α（IFNα）对裸鼠体内人RCC异种移植瘤的宏观肿瘤生长（用外径测量肿瘤大小）和细胞增殖（体内3H-胸腺嘧啶核苷标记指数，LI，和有丝分裂指数，MI）的影响。与未治疗的对照组相比，单独使用这些物质及其联合应用均未以统计学上显著的方式改变治疗组肿瘤大小的时间进程和生长模式。这些治疗对细胞动力学参数也仅有轻微影响，其中单独使用TNFα比单独使用IFNα更有效。然而，与单独使用TNFα的效果相比，与IFNα联合应用可使细胞动力学紊乱得到一定改善，并且肿瘤的生长模式也有明显改变，从单独使用TNFα时明显的Gompertzian模式（单独使用TNFα时）转变为接近指数模式（联合治疗时；p<0.05）。结果，在观察期内联合治疗组的肿瘤生长较慢，另一方面，其生长减速程度不如单独使用TNFα时。实际上，如果肿瘤继续以相同方式生长，根据目前的数据推断，TNFα组和联合治疗组的肿瘤分别比对照肿瘤小和大。值得注意的是，联合应用时IFNα的作用似乎占主导。在这种联合应用对这些荷瘤动物恶病质的影响中也可以看出这一点：单独使用或与TNFα联合使用时，IFNα可部分保护动物免于肿瘤生长相关的体重减轻。尽管目前这种细胞因子联合应用对这种人RCC异种移植瘤的直接体内抗肿瘤作用相当有限，但IFNα对恶病质发展的潜在拮抗作用仍应进一步探索。
