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- ItemSomente MetadadadosAmfenac 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.
- ItemSomente MetadadadosThe effect of a selective cyclooxygenase-2 (COX-2) inhibitor on the proliferation rate of retinoblastoma cell lines(Nature Publishing Group, 2006-05-01) Souza, J. P. de; Corrêa, Zélia Maria da Silva [UNIFESP]; Marshall, J. C.; Anteka, E.; Coutinho, A. B.; Martins, M. C.; Burnier, M. N.; McGill Univ; Universidade Federal de São Paulo (UNIFESP); Retina & Oncol ServPurpose To examine the effect of nepafenac, a selective cyclooxygenase-2 (COX-2) inhibitor, on the proliferation rate of two human retinoblastoma (Rb) cell lines.Methods Two human Rb cell lines (WERI-RB and Y79) were cultured. COX-2 expression in these cell lines was verified by imunocytochemical analysis of cytospin sections and Western blotting. An MTT-based proliferation assay was used to compare Rb cell growth with and without amfenac, the active metabolite of nepafenac. the averaged results per condition were recorded. the Student's t-test was used to compare results from the cells cultured with and without amfenac.Result the Y79 cell line showed a higher proliferative rate than the WERI-RB cell line. Both cell lines were negative for COX-2 expression by immunocytochemical analysis; however, both cell lines were positive for COX-2 expression by Western blot. When amfenac was added to both of the cell lines, a statistically significant reduction in proliferation was observed in both cell lines. the two Rb cell lines were positive for COX-2 only in the Western blot, indicating that they probably express low levels of COX-2, which was undetectable by immucytochemical analysis.Conclusion the selective, anti-COX-2 molecule amfenac inhibited proliferation of both tested Rb cell lines. Further trials should be undertaken to study the effect of selective COX-2 inhibitors on Rb.
- ItemSomente MetadadadosThe effect of imatinib mesylate on the proliferation, invasive ability, and radiosensitivity of retinoblastoma cell lines(Nature Publishing Group, 2013-01-01) Moura, L. R. de; Marshall, J-C; Di Cesare, S.; Fernandes, B. F.; Antecka, E.; Burnier, M. N.; McGill Univ; Henry C Witelson Ocular Pathol Lab; Inst Brasileiro Oftalmol; Universidade Federal de São Paulo (UNIFESP)Purpose Our aim was to evaluate the potential effect of imatinib mesylate (IM), a small molecule that specifically inhibits the tyrosine quinase receptors, on the proliferation and invasive abilities of two human retinoblastoma (Rb) cell lines. Furthermore, the ability of IM to radiosensitize Rb cells was evaluated. the potential targets of IM (C-kit, PDGRF-alpha and -beta, and c-Abl) were also investigated in these cell lines.Methods Two human Rb cell lines (WERI-RB-1 and Y79) were cultured under normal growth conditions. An MTT-based proliferation assay and a Matrigel invasion assay were performed with and without exposure to 10 mu M of IM. the cells were also irradiated with graded dosages of 0, 2, 4, 6, 8, and 10 Gy with and without IM and their proliferations rates were analyzed. Western blot and immunocytochemical analysis of cytospins were performed to evaluate the expression of C-kit, PDGRF-alpha and -beta, and c-Abl.Results When IM was added to both cell lines a statistically significant (P<0.05) reduction in proliferation and invasive ability were observed. Exposure to IM also significantly increased the radiosensitivity of both Rb cell lines. the c-Abl expression was strongly positive, PDGRF-alpha and -beta expression were also positive but the C-kit expression was negative in both cell lines.Conclusions These results indicate that Gleevec may be useful as an adjuvant treatment in Rb patients, specially those considered for radiation therapy. Eye (2013) 27, 92-99; doi:10.1038/eye.2012.231; published online 16 November 2012