Effects of recombinant human interleukin-1 alpha on clonogenic growth of primary human tumors in vitro.

A R Hanauske, D Degen, M H Marshall, S G Hilsenbeck, P Banks, J Stuckey, M Leahy, D D Von Hoff
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引用次数: 10

Abstract

Interleukin-1 alpha (IL-1 alpha) is a low-molecular-weight cytokine that regulates proliferation and differentiation of lymphatic and myeloid cells. It also has pleiotropic activity on a variety of other target cells and acts as an important mediator of inflammation and septic shock. Recombinant human IL-1 alpha (rhIL-1 alpha) is undergoing clinical evaluation of its potential as an anticancer agent. We have studied the growth modulating effects of rhIL-1 alpha on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.01-100 ng/ml were used in continuous incubation experiments. Of 139 specimens tested, 56 (40%) were evaluable for determination of tumor growth modulating activity. The most common tumor types examined included breast, nonsmall cell lung, ovarian, colorectal cancer, and melanoma. Stimulation of tumor colony-forming units (colony formation greater than or equal to 1.5 x controls) was observed in only 1/56 (2%) tumors. No evidence was found for increased size of individual colonies after incubation with rhIL-1 alpha. At a concentration of 100 ng/ml, colony formation of 9/56 (16%) tumor specimens was significantly inhibited (colony formation less than or equal to 0.5 x controls). We conclude that rhIL-1 alpha is not a major modulator of tumor colony formation in vitro. However, some antitumor effects may be observed at high concentrations.

重组人白细胞介素-1 α对人原发肿瘤体外克隆生长的影响。
白细胞介素-1 α (IL-1 α)是一种低分子量的细胞因子,调节淋巴细胞和髓细胞的增殖和分化。它还对多种其他靶细胞具有多效性活性,并作为炎症和感染性休克的重要介质。重组人白细胞介素-1 α (rhIL-1 α)作为抗癌药物的潜力正在进行临床评估。我们利用体外软琼脂克隆系统研究了rhIL-1 α对多种新鲜外植的人肿瘤标本的生长调节作用。连续孵育实验的终浓度为0.01 ~ 100 ng/ml。在测试的139个标本中,56个(40%)可用于测定肿瘤生长调节活性。最常见的肿瘤类型包括乳腺癌、非小细胞肺癌、卵巢癌、结直肠癌和黑色素瘤。肿瘤集落形成单位的刺激(集落形成大于或等于对照的1.5倍)仅在1/56(2%)肿瘤中观察到。没有证据表明与rhIL-1 α孵育后单个菌落的大小增加。在浓度为100 ng/ml时,9/56(16%)肿瘤标本的菌落形成被显著抑制(菌落形成小于或等于对照的0.5倍)。我们得出结论,rhIL-1 α不是体外肿瘤集落形成的主要调节剂。然而,在高浓度下可能观察到一些抗肿瘤作用。
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