The Journal of investigative dermatology. 2005 Aug 15. pii: JID23830. doi: 10.1111/j.0022-202X.2005.23830.x |
Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human melanoma xenotransplatation model. |
Heere-Ress E1, Boehm J, Thallinger C, Hoeller C, Wacheck V, Birner P, Wolff K, Pehamberger H, Jansen B |
Abstract 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. |
Publikations ID: 16098027 Quelle: öffnen |