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A Third-Generation Bisphosphonate, Minodronic Acid (YM529), Augments the Interferon α/β-Mediated Inhibition of Renal Cell Cancer Cell Growth Both In vitro and In vivo

YUASA, Takeshi ; NOGAWA, Masaki ; KIMURA, Shinya ; YOKOTA, Asumi ; SATO, Kiyoshi ; SEGAWA, Hidekazu ; KURODA, Junya ; MAEKAWA, Taira

Clinical cancer research, 2005-01, Vol.11 (2), p.853-859 [Periódico revisado por pares]

Philadelphia, PA: American Association for Cancer Research

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Título:
A Third-Generation Bisphosphonate, Minodronic Acid (YM529), Augments the Interferon α/β-Mediated Inhibition of Renal Cell Cancer Cell Growth Both In vitro and In vivo
Autor: YUASA, Takeshi ; NOGAWA, Masaki ; KIMURA, Shinya ; YOKOTA, Asumi ; SATO, Kiyoshi ; SEGAWA, Hidekazu ; KURODA, Junya ; MAEKAWA, Taira
Assuntos: Animals ; Antineoplastic agents ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; bisphosphonate ; Carcinoma, Renal Cell - drug therapy ; Cell Proliferation - drug effects ; Diphosphonates - therapeutic use ; Drug Therapy, Combination ; Humans ; Imidazoles - therapeutic use ; In Vitro Techniques ; interferon ; Interferon-alpha - therapeutic use ; Interferon-beta - therapeutic use ; Kidney Neoplasms - drug therapy ; Luciferases - metabolism ; Medical sciences ; Mice ; minodronic acid ; Pharmacology. Drug treatments ; rap1 GTP-Binding Proteins - metabolism ; ras Proteins - metabolism ; renal cell cancer ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A - metabolism ; VEGF
É parte de: Clinical cancer research, 2005-01, Vol.11 (2), p.853-859
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Purpose: Minodronic acid (YM529) is a third-generation nitrogen-containing bisphosphonate. Here, we have investigated the therapeutic efficacy of YM529 against renal cell cancer (RCC) alone or in combination with IFN both in vitro and in vivo . Experimental Design: One murine and eight human RCC cell lines were used for the in vitro studies and were subjected to a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting. Luciferase-labeled murine RCC cells (RENCA Luc ) were transplanted into the s.c. tissue or the renal subcapsule of syngeneic BALB/c mice. These mice were treated with YM529 and/or murine IFN and the growth of the cancer cells was monitored by an in vivo imaging system. Results: YM529 inhibited the growth of RCC cells in a dose- and time-dependent manner and enhanced the growth inhibitory potential of IFN in vitro . In the in vivo mouse models, YM529 did not markedly inhibit the RCC cell growth on its own but it augmented the anticancer effect of IFN ( P < 0.05). The YM529-treated mice (with or without IFN) did not alter the γ/δ T-lymphocyte numbers. The various treatment regimens were also not associated with any adverse effects. However, YM529 combined with IFN reduced the serum vascular endothelial growth factor levels. Conclusions: Our study suggests that YM529 may be a potent anticancer agent for RCC. The efficacy and safety of IFN plus YM529 as a therapy for RCC should be verified by early-phase clinical trials.
Editor: Philadelphia, PA: American Association for Cancer Research
Idioma: Inglês

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A Third-Generation Bisphosphonate, Minodronic Acid (YM529), Augments the Interferon α/β-Mediated Inhibition of Renal Cell Cancer Cell Growth Both In vitro and In vivo

YUASA, Takeshi ; NOGAWA, Masaki ; KIMURA, Shinya ; YOKOTA, Asumi ; SATO, Kiyoshi ; SEGAWA, Hidekazu ; KURODA, Junya ; MAEKAWA, Taira

Philadelphia, PA: American Association for Cancer Research

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