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Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.

Kurabayashi A, Inoue K, Fukuhara H, Karashima T, Fukata S, Kawada C, Shuin T, Furihata M - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.

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Related in: MedlinePlus

Effect of YM529 on the number of osteoclasts in bone lesions. (a) At the end of therapy (day 88), bone lesions were harvested and osteoclasts were stained for TRAP. (b) The number of osteoclasts was significantly less in bone lesions of mice treated with YM529 alone or in combination with IFN-α than in control mice or in mice treated with IFN-α alone (*P = 0.0082, **P = 0.0105, ***P = 0.0073, ****P = 0.0101).
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fig05: Effect of YM529 on the number of osteoclasts in bone lesions. (a) At the end of therapy (day 88), bone lesions were harvested and osteoclasts were stained for TRAP. (b) The number of osteoclasts was significantly less in bone lesions of mice treated with YM529 alone or in combination with IFN-α than in control mice or in mice treated with IFN-α alone (*P = 0.0082, **P = 0.0105, ***P = 0.0073, ****P = 0.0101).

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.


Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.

Kurabayashi A, Inoue K, Fukuhara H, Karashima T, Fukata S, Kawada C, Shuin T, Furihata M - Cancer Sci. (2015)

Effect of YM529 on the number of osteoclasts in bone lesions. (a) At the end of therapy (day 88), bone lesions were harvested and osteoclasts were stained for TRAP. (b) The number of osteoclasts was significantly less in bone lesions of mice treated with YM529 alone or in combination with IFN-α than in control mice or in mice treated with IFN-α alone (*P = 0.0082, **P = 0.0105, ***P = 0.0073, ****P = 0.0101).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556400&req=5

fig05: Effect of YM529 on the number of osteoclasts in bone lesions. (a) At the end of therapy (day 88), bone lesions were harvested and osteoclasts were stained for TRAP. (b) The number of osteoclasts was significantly less in bone lesions of mice treated with YM529 alone or in combination with IFN-α than in control mice or in mice treated with IFN-α alone (*P = 0.0082, **P = 0.0105, ***P = 0.0073, ****P = 0.0101).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kochi Medical School, Nankoku, Japan.

Show MeSH
Related in: MedlinePlus