Biomedical subjects

Raquel C Maia

Publications and source records attributed to Raquel C Maia.

5 recordsLinked to original sources

PubMed2006

Contrasting features of MDR phenotype in leukemias by using two fluorochromes: implications for clinical practice.

The expression and activity of P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) were analyzed in 178 leukemia samples. Rhodamine-123 (Rho-123) and DiOC(2) were used as substrate to evaluate efflux pump activity. Chronic myeloid leukemia (CML) exhibited a higher percentage of positivity using Rho-123 than DiOC(2) (p=0.000) as compared to other types of leukemia. Moreover, Rho-123 was able to detected Pgp positive cells in a higher proportion of samples than DiOC(2) samples (p=0.004). Similarly, MRP1 positive cells were best detected by Rho-123 as opposed to DiOC(2) (p=0.003). The co-functionality of Rho-123 and DiOC(2) was observed in 26 out of 105 (24.8%) leukemic samples. Co-expression between Pgp and MRP1 was detected in 30 out of 56 (53.6%) samples. As a whole, when the same samples were analyzed, Rho-123 was able to detect Pgp positive cells in a higher proportion of samples than DiOC(2) (p=0.000). Similarly, MRP1 positive cells were best detected by Rho-123 as opposed to DiOC(2) (p=0.007). Our results support the idea that Rho-123 is the substrate of choice for leukemic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Coexpression of p53 protein and MDR functional phenotype in leukemias: the predominant association in chronic myeloid leukemia.

BACKGROUND: One of the best characterized resistance mechanisms of leukemias is multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) and multidrug-resistant related protein (MRP). In addition to Pgp and MRP, p53 mutation or inactivation might play a relevant role in therapeutic failure. Some studies have demonstrated that Pgp and MRP may be activated in association with overexpression of mutant or inactivated p53 protein. The aim of this study was to investigate the association between p53 expression and MDR functional phenotype analyzed by flow cytometry (FCM). METHODS: Rhodamine-123 assay analyzed by FCM was used to detect the MDR phenotype that was positive in 18 out of 41 (43.9%) cases of chronic myeloid leukemia (CML), 16 out of 28 (57.1%) chronic lymphoid leukemia (CLL) cases, 11 out of 28 (39.3%) acute myeloid leukemia (AML) cases, and four out of 22 (18.2%) acute lymphoid leukemia (ALL) cases. RESULTS: Variable levels of p53 expression were observed in leukemic cells: 12 out of 41 (29.2%) in CML, nine out of 28 (32.1%) in CLL, 15 out of 28 (53.6%) in AML, and eight out of 22 (36.4%) in ALL samples. CONCLUSIONS: In our study, no significant association between p53 expression and MDR functional phenotype was observed in ALL, CLL, and AML. On the other hand, a significant association (P = 0.0003) of the coexpression was observed in CML. The p53 overexpression was more frequently seen in the accelerated phase and the blastic phase of this disease. Our results suggest that an MDR functional phenotype could be associated with p53 mutation in the advanced stage of leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

CPT-11-induced cell death in leukemic cells is not affected by the MDR phenotype.

CPT-11 is a topoisomerase I (Topo I) inhibitor which was initially described as active in multi-drug resistance (MDR) tumors. The MDR phenomenon is characterized by the overexpression of efflux pumps which are able to extrude a range of drugs non-related chemical or functionally. In this work, we treated leukemic cells with CPT-11 300 microM at 24h and compared its cytotoxicity with the activity of efflux pumps and with cell cycle phase. Our findings show that CPT-11 has a potent anti-tumor activity in leukemic cells regardless MDR phenotype and the cell cycle phase, suggesting new avenues to be explored in leukemia treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Mitotracker green is a P-glycoprotein substrate.

P-glycoprotein has a widespread expression on normal tissues. The protein has also been strongly associated with the multidrug resistance phenotype (MDR) on tumor cells. The employment of flow cytometry and confocal microscopy has contributed to the discovery and application of new particular fluorescent dyes. Nevertheless, several studies are being performed in different cellular types neglecting the expression/activity of MDR proteins. Because many fluorochromes have been reported as P-glycoprotein substrates, an especial attention must be given to the properties of new dyes in the presence of MDR proteins. Flow cytometric analyzes of Mitotracker Green (MTG) fluorescence profile were performed in a human erythroleukemic cell line and its resistant counterpart. In this report we demonstrated that MTG, a probe used to evaluate the mitochondrial mass, is a P-glycoprotein substrate and its staining profile is dependent on the activity of this protein. In vitro studies on a human erythroleukemic cell line and its resistant counterpart revealed that MDR modulators (Cyclosporin A, Verapamil, and Trifluoperazine) alter the MTG fluorescence pattern on a resistant cell line. The findings suggest that attention should be given to the expression of P-glycoprotein when performing an evaluation of mitochondria properties with MTG.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I.

T-cell leukemia/lymphoma (T-c LL) associated with prior infection with HTLV-I is rarely described in children. We present herein, the clinical, morphological, and virologic features of T-c LL, which occurred in eight pediatric cases with similar features of ATLL described in adults. There were three girls and five boys with age ranging from 2 to 18 years. Lymphoadenopathy, hepatosplenomegaly and marked skin lesions were presented in all cases. Five patients had hypercalcemia. The diagnostic criteria of T-c LL were based on both morphological and immunophenotypical analyses characterized by T-cell markers positively. Seven cases were cCD3+, CD4/CD25+, whereas CD1a and TdT were negative in all cases tested. HTLV-I antibodies were detected in all cases. HTLV-I provirus integration of at least one provirus was seen in all cases tested by molecular analysis. Mother-to-child transmission of HTLV-I was demonstrated in six cases. Interestingly, a homozygous deletion in p16 gene locus was observed in all four cases studied, while exons 7 and 8 of p53 were deleted in one child. The deletion of the p16(INK4A)/p14(ARF) or mutation of p53, key regulatory protein of cell cycle checkpoint in G1/S progression, found in five of the eight pediatric patients suggests that in these cases genetic lesions associated with HTLV-I infection may predispose for an early onset of leukemia.

Adolescent↗