Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.
Bottom Line: The antiangiogenetic effect by YM529 and/or IFN-α was analyzed using micro-vessel density and in situ mRNA hybridization.Neither YM529 nor IFN-α alone significantly inhibited the growth of established bone metastatic tumors.Their effects are mediated by osteoclast recruitment inhibition and inactivation by YM529 and antiangiogenesis by IFN-α.
Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.Show MeSH
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Mentions: Histological analysis of untreated mice revealed that osteolytic bone lesions comprised cancer cells and that numerous osteoclasts stained for TRAP were observed along the trabecular bone surface surrounded by RBM1-IT4 cells (Fig.5a). The mean number of TRAP-positive osteoclasts in bone tumors counted under a microscope in 10 random microscopy fields at 400×/field was 7.1 ± 2.3 (5.8–10.6) in the control group, 6.1 ± 1.8 (2.9–8.5) in the single-agent-IFN-α group, 2.8 ± 0.7 (2.0–3.5) in the single-agent-YM529 group, and 2.7 ± 0.6 (2.5–3.5) in the combined treatment group (Fig.5b). The number of osteoclasts was significantly lower in bone lesions of mice treated with either YM529 alone or in combination with IFN-α than in those of control mice or in those treated with IFN-α alone (single-agent-YM529 vs control: P = 0.0105; single-agent-YM529 vs single-agent-INF-α: P = 0.0101; combined treatment vs control: P = 0.0082; combined treatment vs single-agent-INF-α: P = 0.0073). There were additive antiproliferative effects of YM529 on osteoclasts in bone tumors.
Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.