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牛眼鳞状细胞癌的局部白细胞介素-2和白细胞介素-12治疗

Local interleukin-2 and interleukin-12 therapy of bovine ocular squamous cell carcinomas.

作者信息

Stewart Rachel J E, Masztalerz Agnieszka, Jacobs John J L, Den Otter Willem

机构信息

Department of Clinical Veterinary Studies, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe.

出版信息

Vet Immunol Immunopathol. 2005 Jul 15;106(3-4):277-84. doi: 10.1016/j.vetimm.2005.03.002. Epub 2005 Apr 15.

Abstract

Interleukin-2 and interleukin-12 have been used independently to successfully treat the induced and the spontaneous tumours in animals. This trial was done to determine if a combination of IL-2 and IL-12 in the treatment of spontaneous bovine ocular squamous cell carcinomas (BOSCC) would be more successful than IL-2 or IL-12 therapy by themselves. For this trial, we selected 25 BOSCC tumours seen on Holstein Fresian cows in Beatrice, Zimbabwe. The cows were randomly assigned to a treatment group of 5 days of IL-2 (200,000 U/day), 5 days of IL-12 (0.5 microg/day) or 5 days of IL-2 (200,000 U/day) and IL-12 (0.5 microg/day). At 20 months after treatment, the IL-2 therapy group had 63% complete regressions; the combination group had 38% complete regressions, which were significantly higher than the IL-12 group, which had 0% complete regressions at 20 months, despite having 29% complete regressions at 6 months. These results show that IL-2 therapy by itself and in combination with IL-12 is more successful than IL-12 by itself. However, combination therapy does not improve the outcome in comparison to IL-2 as a single therapy. It also proves that IL-2 is consistently successful in the therapy of BOSCC with over 60% complete regression, which corresponds to a number of other studies we have done on IL-2 therapy of BOSCC [Rutten, V.P.M.G., Klein, W.R., De Jong, W.A., Misdorp, W., Den Otter, W., Steerenberg, P.A., De Jong, W.H., Ruitenberg, E.J., 1989. Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study. Cancer Immunol. Immunother. 30, 165--169; Stewart, R.J.E., Hill, F.W.G., Masztalerz, A., Jacobs, J.J.L., Koten, J.W., Den Otter, W., 2003. Local low dose interleukin-2 therapy of bovine ocular squamous cell carcinomas in cattle in Zimbabwe, submitted for publication; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H.M., Rutten, V.P.M.G., Ruitenberg, E.J., 1993. Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma. Anticancer Res. 13, 2453-2455; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H., Rhode, C., Stewart, R., Faber, J.A., Ruitenberg, E.J., 1995. Therapy of bovine ocular squamous cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up. Cancer Immunol. Immunother. 41, 10-14].

摘要

白细胞介素 -2 和白细胞介素 -12 已被单独用于成功治疗动物体内诱发的和自发的肿瘤。本试验旨在确定白细胞介素 -2 和白细胞介素 -12 联合治疗自发性牛眼鳞状细胞癌(BOSCC)是否比单独使用白细胞介素 -2 或白细胞介素 -12 治疗更有效。在本次试验中,我们从津巴布韦比阿特丽斯的荷斯坦 - 弗里生奶牛身上选取了 25 个 BOSCC 肿瘤。这些奶牛被随机分配到治疗组,分别接受为期 5 天的白细胞介素 -2(200,000 单位/天)、为期 5 天的白细胞介素 -12(0.5 微克/天)或为期 5 天的白细胞介素 -2(200,000 单位/天)与白细胞介素 -12(0.5 微克/天)联合治疗。治疗后 20 个月,白细胞介素 -2 治疗组有 63% 的完全消退;联合治疗组有 38% 的完全消退,这显著高于白细胞介素 -12 治疗组,后者在 20 个月时完全消退率为 0%,尽管在 6 个月时完全消退率为 29%。这些结果表明,单独使用白细胞介素 -2 以及白细胞介素 -2 与白细胞介素 -12 联合使用比单独使用白细胞介素 -12 更有效。然而,与单独使用白细胞介素 -2 相比,联合治疗并未改善治疗效果。这也证明,白细胞介素 -2 在治疗 BOSCC 方面始终有效,完全消退率超过 60%,这与我们之前进行的多项关于白细胞介素 -2 治疗 BOSCC 的研究结果相符[鲁滕,V.P.M.G.,克莱因,W.R.,德容,W.A.,米斯多普,W.,登奥特,W.,斯特伦伯格,P.A.德容,W.H.,鲁伊滕贝格,E.J.,1989 年。牛眼鳞状细胞癌的局部白细胞介素 -2 治疗。一项初步研究。癌症免疫学与免疫治疗。30,165 - 169;斯图尔特,R.J.E., 希尔,F.W.G., 马兹塔勒兹,A., 雅各布斯,J.J.L., 科滕,J.W., 登奥特,W., 2003 年。津巴布韦牛眼鳞状细胞癌的局部低剂量白细胞介素 -2 治疗,待发表;登奥特,W., 希尔,F.W.G., 克莱因 W.R., 科滕,J.W., 斯特伦伯格,P.A., 德穆尔德,P.H.M., 鲁滕,V.P.M.G., 鲁伊滕贝格,E.J., 1993 年。低剂量白细胞介素 -2 可治愈大型牛眼鳞状细胞癌。抗癌研究。13,2453 - 2455;登奥特,W., 希尔,F.W.G., 克莱因,W.R., 科滕,J.W., 斯特伦伯格,P.A., 德穆尔德,P.H., 罗德,C., 斯图尔特,R., 法伯,J.A., 鲁伊滕贝格 E.J., 1995 年。局部剂量白细胞介素 -2 治疗牛眼鳞状细胞癌:随访 20 个月后完全消退率为 67%。癌症免疫学与免疫治疗。41,10 - 14]。

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