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: mRNA expression of bFGF, VEGF, IL-8, MMP-9, MMP-2, E-cadherin and EGFR was analyzed by ISH (Table3, Fig.6), and MVD was determined by IHC (Fig.7). In RBM1-IT4 cells growing in the tibia of athymic nude mice, bFGF mRNA expression within the tumors of mice treated with IFN-α alone or in combination with YM529 was significantly reduced by 84% (P = 0.0330) and 82% (P = 0.0275), respectively, compared with that in control tumors. Moreover, MVD was significantly lower in tumors treated with IFN-α alone (27.2 ± 5.5) or in combination with YM529 (25.7 ± 9.3) than in control tumors (44.8 ± 11.1; P = 0.0252 and P = 0.0275, respectively) and in those of the single-agent YM529-treated group (39.4 ± 8.2; P = 0.0202 and P = 0.0285, respectively; Fig.7).
Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.