RESUMO
MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of acute myeloid leukemia (AML) with t(8;21), inv(16) or mixed lineage leukemia (MLL) rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor-suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor-suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner.
Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Genes Supressores de Tumor , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Translocação Genética , Animais , Divisão Celular , Criança , Feminino , Citometria de Fluxo , Xenoenxertos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Camundongos NusRESUMO
An experimental and computational investigation of the neutron dose equivalent in the treatment room and maze of various radiotherapy accelerators in Canada was completed. A bubble detector was selected for the bulk of the measurements due to its relative insensitivity to gamma radiation. The rooms and accelerator heads were modelled using the MCNP4B Monte Carlo radiation transport code, modified with a photoneutron patch. The results of the investigation showed generally good agreement between the experiments. Monte Carlo and analytical approximations to the neutron dose equivalent, and suggest that if the analytical approximations are used carefully they may be substituted for more costly experimental or Monte Carlo determinations.
Assuntos
Análise de Falha de Equipamento/métodos , Exposição Ocupacional/análise , Aceleradores de Partículas/instrumentação , Proteção Radiológica/métodos , Radiometria/métodos , Radioterapia/instrumentação , Carga Corporal (Radioterapia) , Simulação por Computador , Monitoramento Ambiental/métodos , Modelos Teóricos , Nêutrons , Doses de Radiação , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
An investigation was performed to examine the neutron dose equivalent in a radiotherapy maze lined with a customised neutron shielding material. The accelerator investigated was a Varian Clinac 2100C/D using 18 MV photons, and the neutron shielding utilised at this centre was Premadex commercially available neutron shielding. Based on Monte Carlo simulations, properly installed customised neutron shielding may reduce the neutron dose equivalent by up to a factor of 8 outside the maze, depending upon the installation. In addition, it was determined that the neutron dose near the entrance to the maze may be reduced by approximately 40% by using customised neutron shielding in the maze, as compared with a facility not using this shielding. This would have a positive dose-saving effect in doorless maze designs.
