Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice

Abstract

Anaplastic thyroid carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-B kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC. [Mol Cancer Ther 2007;6(6):1785 -92]

Sorafenib, a Multikinase Inhibitor, Enhances the Response of Melanoma to Regional Chemotherapy

“…1A), there was a broad spectrum of response ranging from very sensitive (DM833; cell survival, 27% of control) to resistant (DM751; cell survival, 98% of control). No correlation was observed between sensitivity to sorafenib alone measured at 48 hours and BRaf mutation status (P > 0.50), consistent with previous reports (19,31,32).…”

Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in acute myeloid leukemia

“…After only 5 days of sorafenib treatment, the total vessel area in the bone marrow, as indicated by CD31 staining, was significantly reduced (Figure 4, A and B). These results were not unexpected given the known antiangiogenic effects of sorafenib (21,22). However, to directly test our hypothesis, that endothelial VEGF inhibition is sufficient to increase BMX expression in AML cells, we treated MOLM13 cell-bearing NSG mice with 2 VEGF antibodies: bevacizumab, which inhibits tumor-derived human VEGF, and B20, which inhibits murine VEGF.…”

Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload

“…Mice were placed on an iron-deficient diet (~4 ppm iron, Harlan Teklad) for 2 weeks to suppress endogenous hepcidin and to decrease its mouse-to-mouse variability (16,41). Mice were subjected to the following treatments: (42). Mice were sacrificed 4 hours later, and serum iron was determined using a colorimetric assay (Diagnostic Chemicals) (16).…”