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抗白细胞介素4抗体与吲哚美辛对B16黑色素瘤肿瘤进展的协同作用。

Anti-interleukin 4 antibody and indomethacin synergistic effect on B16 melanoma tumor progression.

作者信息

Blaya C, Crespo J, Crespo A, Aliño S F

机构信息

Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.

出版信息

J Pharmacol Exp Ther. 1996 Nov;279(2):472-7.

PMID:8930148
Abstract

B16 melanoma-bearing mice were treated with anti-interleukin 4 antibody, indomethacin or its combination to evaluate the ability of the primary tumor to induce lung metastasis and the antitumor host response. Flow cytometry of tumor cells incubated with sera from tumor-bearing mice showed B16 melanoma to induce a significant antitumor humoral response (39.0 +/- 1.1% positive cells versus 1.8 +/- 0.9% in the control). The treatment of tumor-bearing mice with antimouse anti-interleukin 4 monoclonal antibody plus indomethacin significantly increased (P < .01) the mean value of lung metastasis (from 6.1 +/- 3.0 in the controls to 50.8 +/- 21.8). Also, a significant increase in natural cytotoxicity against tumor cells was observed when both peripheral blood mononuclear cells and splenocytes were used as effector cells. In contrast, an antibody-dependent cellular cytotoxicity decrease was found with effector cells from both normal and tumor-bearing mice. In the former, the antibody-dependent cellular cytotoxicity decrease was 49.4% and 58.4% (P < .05) for peripheral blood mononuclear cells and splenocytes, whereas in the second case the decrease was 40.7% (P < .05) and 29.1% (P < .01), respectively. These results suggest that an efficient antibody-dependent cellular cytotoxicity response might be necessary to secure an effective host antitumor immune response.

摘要

用抗白细胞介素4抗体、吲哚美辛或其组合处理荷B16黑色素瘤的小鼠,以评估原发性肿瘤诱导肺转移的能力和抗肿瘤宿主反应。用荷瘤小鼠血清孵育肿瘤细胞后的流式细胞术显示,B16黑色素瘤可诱导显著的抗肿瘤体液反应(阳性细胞为39.0±1.1%,而对照组为1.8±0.9%)。用抗小鼠抗白细胞介素4单克隆抗体加吲哚美辛处理荷瘤小鼠,可显著增加(P<0.01)肺转移的平均值(从对照组的6.1±3.0增加到50.8±21.8)。此外,当使用外周血单个核细胞和脾细胞作为效应细胞时,观察到对肿瘤细胞的自然细胞毒性显著增加。相反,在正常小鼠和荷瘤小鼠的效应细胞中均发现抗体依赖性细胞毒性降低。在前者中,外周血单个核细胞和脾细胞的抗体依赖性细胞毒性降低分别为49.4%和58.4%(P<0.05),而在后者中,降低分别为40.7%(P<0.05)和29.1%(P<0.01)。这些结果表明,有效的抗体依赖性细胞毒性反应可能是确保有效的宿主抗肿瘤免疫反应所必需的。

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