Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human melanoma xenotransplatation model

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:125

Review

Heere-Ress, E ; Boehm, J ; Thallinger, C ; Hoeller, C ; Wacheck, V ; Birner, P ; Wolff, K ; Pehamberger, H ; Jansen, B

关键词: anti-angiogenesis;    apoptosis;    chemotherapy;    melanoma;    microvessel density;    thalidomide;    TNF-alpha;   

DOI  :  10.1111/j.0022-202X.2005.23830.x

来源: Elsevier

【 摘 要 】

It has been demonstrated that thalidomide's anti-angiogenic properties result in clear anti-tumor activity in a number of human malignancies. We studied thalidomide in a human melanoma severe combined immunodeficiency mouse xenotransplantation model. Thalidomide as a single agent showed a significant tumor reduction of 46% compared with the control group. Thalidomide combined with dacarbazine treatment markedly enhanced the anti-tumor effect of chemotherapy and showed a significant tumor reduction relative to the dacarbazine-only group (61%) and even more tumor reduction (74%) compared with the control group. We also measured clearly reduced levels of tumor necrosis factor-alpha in the thalidomide-treated group. A significantly lower microvessel density was encountered in the thalidomide treatment groups ( thalidomide alone or combined with DTIC), underscoring the anti-angiogenic effect of thalidomide as a single agent as well as in combination with chemotherapy in this model. In line with these results, we observed a nearly 3-fold increase of apoptosis for the combination of thalidomide and DTIC compared with the rate of apoptotic cells in DTIC-only-treated melanoma xenotransplants. These data underline the rationale for combining dacarbazine-a cytotoxic agent-and thalidomide-an anti-angiogenic cytostatic agent-as a promising strategy for the treatment of melanoma.

【 授权许可】

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