Navegando por Palavras-chave "imatinib mesylate"

Agora exibindo 1 - 2 de 2
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib
    (Spandidos Publ Ltd, 2014-04-01) Vivona, Douglas; Lima, Luciene Terezina; Rodrigues, Alice Cristina; Bueno, Carolina Tosin; Steinhorst Alcantara, Greyce Kelly; Ribeiro Barros, Luiza Saldanha; De Moraes Hungria, Vania Tiestsche; Chiattone, Carlos Sergio; Chauffaille, Maria de Lourdes Lopes Ferrari [UNIFESP]; Guerra-Shinohara, Elvira Maria; Universidade de São Paulo (USP); Santa Casa Med Sch; Universidade Federal de São Paulo (UNIFESP)
    Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. the aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. in total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. the patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. in addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. the P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P=0.001). Furthermore, the patients who did not achieve major molecular response (MMR) showed a higher rate of efflux mediated by P-gp when compared with individuals who achieved MMR (64.7 vs. 45.7%; P=0.001). All patients without MMR demonstrated effluxes of >60%. in addition, patients without MMR exhibited lower plasma concentrations of IM compared with those with MMR (0.51 vs. 1.42 mu g/ml; P=0.001). Higher levels of SLC22A1 mRNA were observed in patients who achieved MMR and complete molecular response (P<0.05). in conclusion, the ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with reduced P-gp activity and MMR in chronic-phase CML patients treated with a standard dose of IM.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    The 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