RESUMO
Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.
Assuntos
Antineoplásicos/uso terapêutico , Indazóis/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/metabolismo , Transplante de Medula Óssea , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Transplante HeterólogoRESUMO
A microfluidic biochip for conducting an array of polymerase chain reaction (PCR) simultaneously was fabricated to understand the microfluidic loading process of PCR solution into microfabricated glass reaction chambers. The geometrical factors of the microfluidic structure, including the shape and depth of the microchamber, shape and size of the microchannels were investigated on the formation of air bubbles trapped within the microchamber during the PCR solution loading process. Furthermore, the effects of surface properties of the microfluidic structure, including hydrophilicity of the microchamber and inlet channel, and hydrophobicity of the outlet channel, on the loading of PCR solution, especially on the formation of air bubbles were studied. As a result, the surface wetting property of the microchamber was found to be the main reason for the formation of the air bubbles inside the microchamber during the loading of PCR solution in the biochips. A solution to avoid the air trapping has been proposed and investigated.