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: All animal experiments were conducted with care in a manner approved by the Guide for Animal Care and Use Committee of Kochi Medical School. Mice were anesthetized with Nembutal. For ectopic implantation, a percutaneous intraosseal injection was made by drilling a 27-gauge needle into the proximal side of the tibia. After penetration of the cortical bone, RBM1-IT4 cells (2 × 106 cells/20-μL medium) were injected. After 2 months, mice with tumor growth demonstrated on soft X-ray images were randomly separated into four groups. Mice in each group were treated for 4 weeks with i.p. injections of either physiological saline (control) or YM529 (0.3 mg/kg/week), and/or s.c. injections of physiological saline and IFN-α (100 IU/day), according to the schedule shown in Figure1. Tumors were harvested on day 88 after implantation.
Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.