RESUMO
Livin, a novel member of the human inhibitors of apoptosis protein family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. The present study was designed to investigate the potential of using RNA interference (RNAi) technique to downregulate Livin expression, and the subsequent effect on human glioma cells. The results showed that knockdown of Livin expression by short interfering RNA (siRNA) significantly inhibited glioma cell proliferation and increased cell apoptosis through cell arrest in the G(1)/G(0) phase of cell cycle in vitro. Furthermore, Livin siRNA significantly suppressed tumor growth in nude mice. Together, these findings suggest that RNAi-mediated downregulation of Livin expression could lead to potent antitumor activity in glioma cells and might serve as a novel therapeutic strategy in clinic.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , Glioma/patologia , Glioma/prevenção & controle , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , RNA Interferente Pequeno/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Western Blotting , Ciclo Celular , Proliferação de Células , Ensaio de Unidades Formadoras de Colônias , Citometria de Fluxo , Glioma/metabolismo , Glioma/mortalidade , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
The purpose of this study is to assess the potential of dendritic cells transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR) assay and kidney function were analyzed. The results demonstrated that after administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad-PD-L1 could improve kidney function and survival of transplants. The findings suggested that DC/Ad-PD-L1 could induce CD8+ T cell tolerance and lead to kidney allograft tolerance, which provided a promising finding for clinical application.
Assuntos
Antígeno B7-H1/imunologia , Células Dendríticas/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/imunologia , Tolerância ao Transplante/imunologia , Adenoviridae/genética , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Western Blotting , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Técnicas de Cocultura , Células Dendríticas/metabolismo , Células HEK293 , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-2/imunologia , Interleucina-2/metabolismo , Transplante de Rim/métodos , Teste de Cultura Mista de Linfócitos , Masculino , Proteinúria/imunologia , Proteinúria/urina , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Análise de Sobrevida , Linfócitos T/metabolismo , Fatores de Tempo , Transfecção , Transplante HomólogoRESUMO
BACKGROUND: Transcatheter closure of atrial septal defects (ASDs) is currently a reliable alternative to surgery, even though challenging in patients with multiple ASDs. HYPOTHESIS: The aim of this study was to evaluate the clinical efficiency and safety of transcatheter closure in multiple ASDs. METHODS: Multiple ASDs were diagnosed by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). The occlusive condition and distance between 2 adjacent ASDs were measured by TTE examination. Then, the number and size of the occluder(s) was determined. TTE examinations were performed after transcatheter closure as follow-up. RESULTS: The transcatheter procedure was successful in 15 patients with multiple ASDs, using a single occluder in 9 patients and 2 occluders in the remaining 6 patients. Overall, 21 ASD occluders were implanted. During a follow-up period of 6 mo to 5 y, a slight residual shunt was found in 1 patient without any symptoms; a moderate residual shunt was identified at the inferior vena cava and the occluder was removed by surgery 1 mo after procedure. Other complications, including endocarditis, arrhythmia, thromboembolism, and atrioventricular valve damage were not recorded in any of the 15 patients during the follow-up period. CONCLUSION: Transcatheter closure of multiple ASDs is safe and efficient. Two occluders are necessary for the distance of 2 ASDs more than 7 mm, and a single occluder is sufficient for those 7 mm or less.