RESUMO
The ataxia telangiectasia-mutated (ATM) protein, which is mutated in the inherited disease ataxia telangiectasia (AT), is a key activator of cell cycle checkpoint, initiating cell response to DNA damage and ensuring genomic stability. AT cells exhibit defects in all cellular responses to ionizing radiation and radiomimetic chemicals. Inactivation of ATM may therefore make cells fail to execute many responses to DNA damage and improve the cells' sensitivity to radiation. Recent developments in the use of small interference RNA molecules (siRNAs) to inhibit specific protein expression have highlighted the potential use of siRNA as a therapeutic agent. In this study, we have designed and exogenously delivered plasmids encoding siRNAs targeting ATM to human cervical carcinoma SiHa cells and generated a stable cell line, SiHa(ATM). SiHa(ATM) cells displayed minimal levels of ATM protein and showed a marked increase in sensitivity to radiation. Together, these data provide strong evidence for the potential use of siRNA as a novel radiation/chemotherapy-sensitizing agent.
Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Sobrevivência Celular/efeitos da radiação , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Tolerância a Radiação/fisiologia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Neoplasias do Colo do Útero/patologia , Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patologia , Proteínas Mutadas de Ataxia Telangiectasia , Western Blotting , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta à Radiação , Feminino , Citometria de Fluxo , Humanos , Fosforilação/efeitos da radiação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Radiação Ionizante , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/genéticaRESUMO
The 6Fr Hydrolyser thrombectomy catheter for acute myocardial infarction (AMI) successfully removed a massive thrombus in the coronary artery in three patients. The 6Fr Hydrolyser catheter could be advanced into the right coronary artery with bare-wire methods via a 6Fr sheath at the radial artery. This approach suggests that the device can be an alternative method for thrombolysis in selected AMI patients with massive thrombus in the coronary artery.
