RESUMO
Overcoming cisplatin-based drug resistance in lung cancer remains an enormous challenge in clinical tumor therapy worldwide. Recent studies have reported that some Rab GTPases are involved in multiple aspects of tumor progression, including invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. In particular, Rab26 is essential to vital processes such as vesicle-mediated secretion, cell growth, apoptosis, and autophagy. In this study, we developed a nanosystem based on programmed DNA self-assembly of Rab26 siRNA-loaded nanoparticles (siRNP). We demonstrated that siRNP could be effectively transfected into cisplatin-resistant A549 (A549/DDP) cells. These siRab26-carrying nanoparticles induced apoptosis and inhibited the disruption of autophagy. The combination therapy of siRab26 knockdown with cisplatin could improve the antitumor therapy compared with a single one in vitro. In nude mice, siRNP enhanced the chemosensitivity of cisplatin-resistant cells and inhibited tumor xenograft development. These outcomes suggest that siRNP is an effective platform for lung cancer therapy in cases exhibiting drug resistance.
Assuntos
Antineoplásicos , Neoplasias Pulmonares , Nanoestruturas , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proliferação de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/farmacologiaRESUMO
Currently, a single treatment is less effective for triple-negative breast cancer (TNBC) therapy. Additionally, there are some limitations to the use of siRNA alone as a new method to treat breast cancer, such as its effective delivery into cells. In this study, we proposed a strategy that combines a siRNA-loaded DNA nanostructure and genistein for TNBC therapy. Both CD36 siRNA-loaded self-assembled DNA nanoprisms (NP-siCD36) and genistein knocked down CD36, resulting in enhanced anticancer efficacy through phosphorylation of the p38 MAPK pathway.In vitrostudies showed that combination therapy could effectively enhance cell apoptosis and reduce cell proliferation, achieving an antitumor effect in TNBC cells. The current study suggests that NP-siCD36 combined with genistein might be a promising strategy for breast cancer and treatment.
Assuntos
Antineoplásicos , Antígenos CD36/genética , Nanoestruturas/química , RNA Interferente Pequeno/genética , Neoplasias de Mama Triplo Negativas , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antígenos CD36/metabolismo , Linhagem Celular Tumoral , DNA/química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Feminino , Genisteína/metabolismo , Genisteína/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
As an emerging imaging technique, thoracic ultrasonography (TUS) is increasingly utilized in the diagnosis of lung diseases in children and newborns, especially in emergency and critical settings. This systematic review aimed to estimate the diagnostic accuracy of TUS in childhood pneumonia. We searched Embase, PubMed, and Web of Science for studies until July 2023 using both TUS and chest radiography (CR) for the diagnosis of pediatric pneumonia. Two researchers independently screened the literature based on the inclusion and exclusion criteria, collected the results, and assessed the risk of bias using the Diagnostic Accuracy Study Quality Assessment (QUADAS) tool. A total of 26 articles met our inclusion criteria and were included in the final analysis, including 22 prospective studies and four retrospective studies. The StataMP 14.0 software was used for the analysis of the study. The overall pooled sensitivity was 0.95 [95% confidence intervals (CI), 0.92-0.97] and the specificity was 0.94 [95% CI, 0.88-0.97], depicting a good diagnostic accuracy. Our results indicated that TUS was an effective imaging modality for detecting pediatric pneumonia. It is a potential alternative to CXR and a follow-up for pediatric pneumonia due to its simplicity, versatility, low cost, and lack of radiation hazards.