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沙利度胺单独及与卡莫司汀联合对C6大鼠胶质瘤的抗增殖作用

Antiproliferative effect of thalidomide alone and combined with carmustine against C6 rat glioma.

作者信息

Arrieta Oscar, Guevara Patricia, Tamariz Joaquin, Rembao Daniel, Rivera Erika, Sotelo Julio

机构信息

Neuroimmunology Unit, National Institute of Neurology and Neurosurgery of México, México.

出版信息

Int J Exp Pathol. 2002 Apr;83(2):99-104. doi: 10.1046/j.1365-2613.2002.00219.x.

Abstract

Thalidomide could have therapeutic applications in neoplasms and in other diseases, particularly those of autoimmune origin. The objective of this study was to investigate the effect of various doses of thalidomide on the growth of C6 glioma in rats, and to determine its effects on parameters of cell proliferation and angiogenesis. Additionally, we investigated a potential enhancement of the antitumoral action of thalidomide when combined with a low dose of the antineoplastic carmustine. C6 glioma cells were implanted subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of animals. When the tumour reached 2.0 cm diameter thalidomide was administered at doses of 100, 200 or 400 mg/kg/day. When given at a dose of 400 mg/kg/day thalidomide significantly reduced the tumour volume, the mitotic index and cell proliferation but not the vascular density. The combination of thalidomide plus carmustine increased the inhibitory effect on tumoral growth. Our results indicate that thalidomide is effective against malignant glioma; apparently by an antiproliferative effect, rather than by inhibition of angiogenesis; when combined with carmustine it could increase the response of glioma to antineoplastic treatment.

摘要

沙利度胺在肿瘤及其他疾病,尤其是自身免疫性疾病中可能具有治疗应用价值。本研究的目的是探讨不同剂量的沙利度胺对大鼠C6胶质瘤生长的影响,并确定其对细胞增殖和血管生成参数的作用。此外,我们还研究了沙利度胺与低剂量抗肿瘤药卡莫司汀联合使用时,其抗肿瘤作用是否会增强。将C6胶质瘤细胞皮下植入Wistar大鼠体内。80%的动物发生了高度恶性的胶质瘤。当肿瘤直径达到2.0 cm时,给予沙利度胺,剂量为100、200或400 mg/kg/天。当以400 mg/kg/天的剂量给药时,沙利度胺显著降低了肿瘤体积、有丝分裂指数和细胞增殖,但对血管密度没有影响。沙利度胺加卡莫司汀的联合用药增强了对肿瘤生长的抑制作用。我们的结果表明,沙利度胺对恶性胶质瘤有效;显然是通过抗增殖作用,而不是通过抑制血管生成;与卡莫司汀联合使用时,它可以增强胶质瘤对抗肿瘤治疗的反应。

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本文引用的文献

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Inhibition of angiogenesis decreases alveolarization in the developing rat lung.抑制血管生成会减少发育中大鼠肺的肺泡化。
Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L600-7. doi: 10.1152/ajplung.2000.279.3.L600.
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Antiangiogenic strategies and agents in clinical trials.临床试验中的抗血管生成策略与药物
Oncologist. 2000;5 Suppl 1:20-7. doi: 10.1634/theoncologist.5-suppl_1-20.
5
Mechanism of action in thalidomide teratogenesis.沙利度胺致畸作用的作用机制。
Biochem Pharmacol. 2000 Jun 15;59(12):1489-99. doi: 10.1016/s0006-2952(99)00388-3.
6
Thalidomide: current and potential clinical applications.沙利度胺:当前及潜在的临床应用
Am J Med. 2000 Apr 15;108(6):487-95. doi: 10.1016/s0002-9343(99)00408-8.
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Analgesic effect of thalidomide on inflammatory pain.沙利度胺对炎性疼痛的镇痛作用。
Eur J Pharmacol. 2000 Mar 10;391(1-2):97-103. doi: 10.1016/s0014-2999(99)00918-8.

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