ABSTRACT
Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups:group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai?ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain?ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P<0.01). By contrast, the mRNA transcription level of PDGFR-β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372;t=2.91;P<0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P<0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P<0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB ( r=0.806, P<0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.
ABSTRACT
Se evaluaron 43 pacientes adultos con leucemia mieloide crónica, Philadelphia positivo, que recibieron tratamiento con mesilato de imatinib como droga de segunda línea por resistencia o intolerancia al interferón alfa recombinante. La manifestación más frecuente al inicio de la enfermedad fue la esplenomegalia. El tratamiento con mesilato de imatinib se inició por resistencia (33; 76,7 por ciento) o intolerancia grado 3 o 4 (10; 23,3 por ciento). El mayor porcentaje de respuesta citogenética mayor (22; 91,7 por ciento) y completa (11; 61,1 por ciento) se alcanzó a los 18 y 24 meses de evolución. El 74,3 por ciento no mostró respuesta molecular y el 5,1 por ciento ya presentaba respuesta molecular antes del tratamiento; 9 (26,5 por ciento) mostraron pérdida de la remisión hematológica completa, de ellos, 7 fallecieron por progresión de la enfermedad. La sobrevida global fue de 90,7 por ciento, 83,3 por ciento, 82,6 por ciento y 78,9 por ciento a los 5, 6, 7 y 8 años de evolución, respectivamente. La sobrevida global y libre de eventos a los 3 años de iniciado el mesilato de imatinib fue de 92,3 por ciento y 81,8 por ciento, respectivamente. Se encontró diferencia significativa entre la sobrevida libre de eventos y el índice pronóstico de Sokal. Las reacciones clínicas secundarias más frecuentes fueron dolores óseos, musculares o ambos; y las hematológicas: anemia hemolítica autoinmune y trombocitopenia
Forty three patients presenting with chronic positive-Philadelphia myeloid leukemia were assessed treated with Imatinib Mesilate as a second line drug by resistance or intolerance to recombinant alpha Interferon. At onset, the more frequent manifestation of this condition was the splenomegalia. Imatinib Mesilate treatment was started by resistance (33; 7.6 percent) or 3 or 4 degree intolerance (10; 23.3 percent). The greater percentage of cytogenetic response (22; 91.7 percent) and complete (11; 61.1 percent) was achieved at 18 and 24 course months. The 74,3 percent hadn't ,molecular response and the 5,1 percent yet had it before treatment; 9 (26.5 percent) showed a loss of complete hematologic remission, from them, 7 deceased from disease progression. Global survival was of 90.7 percent, 83,3 percent