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- 저자 : Moiraghi, Beatriz (검색결과 3 건)
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MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia
Mabel Lardo,Marcelo Castro,Beatriz Moiraghi,Francisca Rojas,Natalia Borda,Jorge A Rey,Alberto Lazarowski 대한혈액학회 2015 Blood Research Vol.50 No.3
BackgroundTyrosine kinase inhibitors (TKIs) are the recommended treatment for patients with chronic myeloid leukemia (CML). The MDR1/ABCB1 gene plays a role in resistance to a wide spec-trum of drugs, including TKIs. However, the association of MDR1/ABCB1 gene poly-morphisms (SNPs) such as C1236T, G2677T/A, and C3435T with the clinical therapeutic evolution of CML has been poorly studied. We investigated these gene polymorphisms in CML-patients treated with imatinib, nilotinib and/or dasatinib.MethodsABCB1-SNPs were studied in 22 CML-patients in the chronic phase (CP) and 2 CML-pa-tients in blast crisis (BC), all of whom were treated with TKIs, and compared with 25 healthy controls using nested-PCR and sequencing techniques.ResultsSeventeen different haplotypes were identified: 7 only in controls, 6 only in CML-patients, and the remaining 4 in both groups. The distribution ratios of homozygous TT-variants present on each exon between controls and CML-patients were 2.9 for exon 12, and 0.32 for the other 2 exons. Heterozygous T-variants were observed in all controls (100%) and 75% of CML-patients. Wt-haplotype (CC-GG-CC) was observed in 6 CML-patients (25%). In this wt-group, two were treated with nilotinib and reached a major molecular response. The remaining 4 cases had either a minimal or null molecular response, or developed bone marrow aplasia.ConclusionOur results suggest that SNPs of the MDR1/ABCB1 gene could help to characterize the prognosis and the clinical-therapeutic evolution of CML-patients treated with TKIs. Wt-haplotype could be associated with a higher risk of developing CML, and a worse clin-ical-therapeutic evolution.
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MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia
Mabel Lardo,Marcelo Castro,Beatriz Moiraghi,Francisca Rojas,Natalia Borda,Jorge A Rey,Alberto Lazarowski 대한혈액학회 2015 Blood Research Vol.50 No.3
BackgroundTyrosine kinase inhibitors (TKIs) are the recommended treatment for patients with chronic myeloid leukemia (CML). The MDR1/ABCB1 gene plays a role in resistance to a wide spec-trum of drugs, including TKIs. However, the association of MDR1/ABCB1 gene poly-morphisms (SNPs) such as C1236T, G2677T/A, and C3435T with the clinical therapeutic evolution of CML has been poorly studied. We investigated these gene polymorphisms in CML-patients treated with imatinib, nilotinib and/or dasatinib.MethodsABCB1-SNPs were studied in 22 CML-patients in the chronic phase (CP) and 2 CML-pa-tients in blast crisis (BC), all of whom were treated with TKIs, and compared with 25 healthy controls using nested-PCR and sequencing techniques.ResultsSeventeen different haplotypes were identified: 7 only in controls, 6 only in CML-patients, and the remaining 4 in both groups. The distribution ratios of homozygous TT-variants present on each exon between controls and CML-patients were 2.9 for exon 12, and 0.32 for the other 2 exons. Heterozygous T-variants were observed in all controls (100%) and 75% of CML-patients. Wt-haplotype (CC-GG-CC) was observed in 6 CML-patients (25%). In this wt-group, two were treated with nilotinib and reached a major molecular response. The remaining 4 cases had either a minimal or null molecular response, or developed bone marrow aplasia.ConclusionOur results suggest that SNPs of the MDR1/ABCB1 gene could help to characterize the prognosis and the clinical-therapeutic evolution of CML-patients treated with TKIs. Wt-haplotype could be associated with a higher risk of developing CML, and a worse clin-ical-therapeutic evolution.
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Cortes, Jorge E.,Baccarani, Michele,Guilhot, Franç,ois,Druker, Brian J.,Branford, Susan,Kim, Dong-Wook,Pane, Fabrizio,Pasquini, Ricardo,Goldberg, Stuart L.,Kalaycio, Matt,Moiraghi, Beatriz,Rowe, American Society of Clinical Oncology 2010 Journal of clinical oncology Vol.28 No.3
<B>Purpose</B><P>To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase.</P><B>Patients and Methods</B><P>A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months.</P><B>Results</B><P>At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d.</P><B>Conclusion</B><P>MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.</P>
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