RESUMEN
The objective of this meta-analysis is to evaluate the association between LncRNA MALAT1 and the clinicopathological characteristics and prognosis in patients with bladder cancer. Related studies were searched from Pubmed, Embase, Cochrane Library, CNKI and Web of Science up to Sep 1, 2021. Basic characteristic and prognostic data were extracted from the included studies. We synthesized and compared primary outcomes such as overall survival. Based on the cut-off value, sample size, and follow-up time, subgroup analysis was conducted. We calculated the combined hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) to assess the relationship between LncRNA MALAT1 and prognosis clinicopathological features of bladder cancer patients. Seven studies with 822 patients were included in this meta-analysis. The results showed that the high lncRNA MALAT1 was significantly related to poor overall survival (HR = 2.34, 95% CI:1.61-3.38; P<0.001) in bladder cancer patients. Furthermore, a high level of LNCRNA MALAT1 is associated with lymph node metastasis (LNM) (OR = 1.82, 95% CI 1.32-2.52, P <0.001) in bladder cancer. The results of sensitivity analysis showed the stabilization and reliability of results in this Meta-analysis. In conclusion, elevated LncRNA MALAT1 is associated with a poor prognosis and a higher risk of LNM in patients with bladder cancer. LncRNA MALAT1 could be identified as a biomarker with a potential prognostic value in bladder cancer.
Asunto(s)
Neoplasias , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , ARN Largo no Codificante/genética , Reproducibilidad de los Resultados , Biomarcadores de Tumor/genética , Neoplasias de la Vejiga Urinaria/genética , Modelos de Riesgos Proporcionales , Metástasis Linfática , Neoplasias/genéticaRESUMEN
The present study aims to evaluate the anticancer effect of L-securinine on androgen-independent prostate cancer (AIPC) DU145 cells. L-securinine (2.5, 5, and 10 µM) treatment for 24, 48 and 72 h displayed strong growth inhibitory effect on DU145 cells in a concentration and time-dependent fashion but has less toxicity toward normal androgen-dependent LNCaP cells. Hoechst 332582 staining of DU145 cells and Annexin V-FITC/ PI dual-labeling followed by flow cytometry assay identified that this growth inhibition by L-securinine would be due to the induction of apoptosis. Moreover Transwell assay revealed that L-securinine significantly inhibited the cell migration/invasion ability of DU145 cells. Furthermore, results of western blotting showed that the involvement of mitochondrial apoptotic pathway in the L-securinine-induced apoptosis of DU145 cell, as evidenced by an increase in the protein expression of Bax, cleaved caspase-9, cleaved caspase-3, cytosolic cytochrome c, and cleaved PARP, together with a unchanged cleaved caspase-8 and decreased Bcl-2 protein expression. Also, L-securinine-induced antimetastatic activity in DU145 cells was associated with decreased protein expression of MMP-2 and MMP-9 and concurrent reduction of VEGF. In addition, further studies revealed that L-securinine may inhibit the protein expression of AGTR1, p-MEK1/2, p-ERK1/2, p-STAT3, PAX2, and p-PAX2, while the expression of ERK1/2, MEK1/2, and STAT3 protein retains intact. These findings suggest that L-securinine may be a promising chemopreventive agent against AIPC.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Azepinas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Compuestos Heterocíclicos de Anillo en Puente/farmacología , Lactonas/farmacología , Mitocondrias/efectos de los fármacos , Piperidinas/farmacología , Apoptosis/genética , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 9/genética , Caspasa 9/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , MAP Quinasa Quinasa 1/genética , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/genética , MAP Quinasa Quinasa 2/metabolismo , Masculino , Mitocondrias/genética , Mitocondrias/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factor de Transcripción PAX2/genética , Factor de Transcripción PAX2/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Objective The present study was performed to explore the therapeutic potential of simvastatin in subarachnoid hemorrhage (SAH) in the context of the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) trial. Methods MEDLINE, EMBASE, and the Cochrane Library were searched for all randomized controlled trials (RCTs) investigating the therapeutic effect of simvastatin on aneurysmal SAH. We applied a random-effects model to calculate the data. Results Five RCTs involving 951 patients met the eligibility criteria. We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55-1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63-1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67-1.54). Subgroup analysis showed that these consolidated results were stable at different doses, different times to start of treatment, and different courses of treatment in all included RCTs. Sensitivity analysis showed that the STASH trial, which had a large population, did not influence the consolidated results of all three outcomes. Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage.