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重组人白细胞介素-4对新鲜分离的人肿瘤细胞体外集落形成无影响。

Lack of effects of recombinant human interleukin-4 on in vitro colony formation of freshly explanted human tumor cells.

作者信息

Hanauske A R, Degen D, Marshall M H, Trotta P P, Von Hoff D D

机构信息

Technische Universität München, Abteilung Hämatologie und Onkologie, Klinikum rechts der Isar, Germany.

出版信息

Invest New Drugs. 1992 Nov;10(4):269-73. doi: 10.1007/BF00944180.

Abstract

Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.1 to 10 ng/ml were used in continuous incubation experiments. Of 147 specimens, 73 (50%) were evaluable for the determination of tumor growth modulating activity. The most common tumor types recruited included breast, non-small cell lung, ovarian cancer and melanoma. Stimulation of tumor colony forming units (colony formation > or = 1.5 x controls) was observed in 0/73 tumors. Similarly, only 1/73 (1.3%) specimens (a non-small cell lung cancer) had a significant decrease in tumor colony forming units (colony formation < or = 0.5 x controls) at 1 ng/ml. We conclude that rhuIL-4 is not a direct modulator of tumor colony formation in vitro. However, antitumor effects could perhaps be achieved in vivo via the immune-modulating effects of Interleukin-4.

摘要

白细胞介素-4是一种具有高度多效性的由T细胞衍生的淋巴因子,据报道它能刺激宿主细胞介导的抗肿瘤反应。重组人白细胞介素-4(rhuIL-4)目前正处于临床I期试验阶段。我们使用体外软琼脂克隆系统研究了rhuIL-4对各种新鲜分离的人类肿瘤标本的生长调节作用。在连续孵育实验中使用的终浓度为0.1至10 ng/ml。在147个标本中,73个(50%)可用于评估肿瘤生长调节活性。纳入的最常见肿瘤类型包括乳腺癌、非小细胞肺癌、卵巢癌和黑色素瘤。在0/73个肿瘤中观察到肿瘤集落形成单位的刺激(集落形成>或=1.5倍对照)。同样,只有1/73(1.3%)个标本(一个非小细胞肺癌)在1 ng/ml时肿瘤集落形成单位有显著减少(集落形成<或=0.5倍对照)。我们得出结论,rhuIL-4在体外不是肿瘤集落形成的直接调节剂。然而,也许可以通过白细胞介素-4的免疫调节作用在体内实现抗肿瘤作用。

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