Navegando por Palavras-chave "amfenac"

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    Amfenac increases the radiosensitivity of uveal melanoma cell lines
    (Nature Publishing Group, 2008-05-01) Fernandes, B. F.; Marshall, J-C; Di Cesare, S.; Logan, P.; Maloney, S.; Burnier Júnior, Miguel Noel Nascente [UNIFESP]; McGill Univ; Henry C Witelson Ocular Pathol Lab; Universidade Federal de São Paulo (UNIFESP)
    Purpose To evaluate the proliferation rates of five human uveal melanoma (UM) cell lines after treatment with amfenac, a cyclooxygenase (COX)-2 inhibitor, and subsequent radiation exposure.Methods Five human UM cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1) and one human fibroblast cell line (BJ) were incubated with amfenac. Treated and non-treated cell lines were then exposed to various doses of gamma radiation: 0, 2, 4, 6, and 8 Gy. Sulphorhodamine-B assay was used to assess proliferation rates 48 h post-radiation.Results Treatment of UM cell lines with amfenac prior to radiation led to a marked reduction in proliferation rates. This difference was statistically significant in all cell lines at every radiation dose (P < 0.005), with the exception of 92.1 at 2 Gy (P=0.157). Fibroblasts treated with amfenac showed significantly higher proliferation rates after 2 and 8 Gy, with no significant differences at 0, 4, and 6 Gy.Conclusions the radiosensitivity of UM cell lines was increased by the administration of amfenac, the active metabolite of nepafenac. There appears to be a radioprotective effect of amfenac on human fibroblasts. the topical administration of nepafenac may decrease tumour recurrence and radiation-induced complications while broadening the indications for radiotherapy by treating larger tumours.
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    Efeitos do anfenaco e de sua combinação com bevacizumabe sobre a secreção de citocinas pró-angiogênicas e inflamatórias pelas células do epitélio pigmentado retiniano
    (Universidade Federal de São Paulo (UNIFESP), 2015-06-30) Miyamoto, Cristina [UNIFESP]; Burnier Junior, Miguel Noel Nascentes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: To evaluate the effects of amfenac (the active component of nepafenac) and its combination with bevacizumab on the secretion of pro-angiogenic and inflammatory cytokines by human retinal pigment epithelial cells. Additionally, to evaluate if chemical hypoxia with cobalt chloride, a hypoxia-mimicking agent, produces the same effect of the real hypoxia (hypoxia chamber) on the secretion of these cytokines by human retinal epithelial cells. METHODS: ARPE-19 cells were incubated under normoxia, chemical hypoxia, and real hypoxia. The cells were treated as follows: control, bevacizumab (0,25 mg/mL), amfenac (2 ng/mL), and the combination of bevacizumab (0,25 mg/mL) and amfenac (2,0 ng/mL). Media was harvested after 24h for sandwich ELISA-based angiogenesis and inflammation assays. The secretion of 10 pro-angiogenic cytokines: angiogenin, ANG-2, EGF, bFGF, HB-EGF, PDGF-BB, leptin, PIGF, HGF e VEGF; as well as of 10 inflammatory cytokines: IL-1?, IL-1?, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-?, TNF-?, MCP-1, were measured. The viability/cytotoxicity was also assessed. RESUTS: Under normoxia, amfenac increased the secretion of ANG-2, HB-EGF, leptin, PDGF-BB, and PIGF, almost did not changed the secretion of EGF, and reduced the secretion of angiogenin, bFGF, HGF, and VEGF by ARPE-19 cells; the combination of the drugs elevated the secretion of all pro-angiogenic cytokines, except angiogenin, bFGF, and VEGF, whose secretion was diminished. Under chemical hypoxia, amfenac decreased the secretion of all pro-angiogenic cytokines, except ANG-2, whose secretion was increased, EGF whose secrection was practically unchanged and PIGF whose secretion was not detected by the method after the three treatments; the combination of the drugs reduced the secrection of all pro-angiogenic cytokines, except ANG-2 and HGF whose secretion were raised, and PIGF whose secretion was virtually the same. Under real hypoxia, amfenac increased the secretion of all pro-angiogenic cytokines, except angiogenin, bFGF and VEGF, whose secretion was decreased; the combination of the drugs increased the secretion of all pro-angiogenic cytokines, except VEGF. Under normoxia, amfenac practically did not altered the secretion of IL-1? and IL-13, reduced the secretion of IL-1?, IL-4, IL-8, and IL-10, and increased the secretion of IL-6, MCP-1, and TNF-?; the combination of the drugs virtually did not modified the secretion of IL-1?, IL-8, and IL-10, diminished the secretion of IL-1?, and increased the secretion of the remaining inflammatory cytokines. Under chemical hypoxia, amfenac practically did not changed the secretion of IL-1?, IL-1?, and IFN-?, reduced the secretion of IL-10, IL-13, and TNF-?, and elevated the secretion of all other inflammatory cytokines; the combination of the drugs virtually did not modified the secretion of IL-1?, decreased the secretion of IL-10, IL-13, and TNF-?, and increased the secretion of the remaining inflammatory cytokines. Under real hypoxia, amfenac reduced the secretion of all inflammatory cytokines; the combination of the drugs also decreased the secretion of the inflammatory cytokines apart from IFN-?, whose secretion increased; the combination of the drugs caused a more pronounced reduction in the secretion of the inflammatory cytokines (except MCP-1) compared to bevacizumab. These results were not statistically significant. All the treatments did not reduced the viability of the ARPE-19 cells under normoxia, chemical hypoxia and real hypoxia. Comparing the chemical hypoxia with cobalt chloride and the real hypoxia, the chemical hypoxia produced statistically different results regarding the secretion of 8 out of 10 pro-angiogenic cytokines (except EGF and HB-EGF), and the secretion of two inflammatory cytokines (IL-6 and IL-8). CONCLUSIONS: Amfenac reduced the secretion of pro-angiogenic cytokines (angiogenin, bFGF, and VEGF) and the secretion of all inflammatory cytokines under real hypoxia. Besides, except from MCP-1 and IFN-?, the combination of amfenac with bevacizumab tends to cause higher reduction of the levels of inflammatory cytokines secreted by ARPE-19 cells under real hypoxia than bevacizumab alone. Nepafenac may be a worth therapy for exudative AMD in combination with bevacizumab with additional benefits like the reduction of the frequency of intravitreal injections of anti-VEGF. Further studies are necessary to confirm this hypothesis. Compared with real hypoxia, the chemical hypoxia produced different results, sometimes statistically significant, regarding the levels of the pro-angiogenic and inflammatory cytokines secreted by ARPE-19 cells. This suggests that some cytokines function primarily associated with HIF-1?, while others do not.