RESUMEN
BACKGROUND: Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs. METHODS: Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot. RESULTS: The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C. CONCLUSION: This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells.
Asunto(s)
Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Fenotipo , Células Madre Neoplásicas/patología , Proliferación Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
Objective: The aim of this article is to compare the efficacy and safety of doripenem for bacterial infections. Methods: We included six randomized clinical trials identified from PubMed and Embase up to July 31, 2014. The included trials compared efficacy and safety of doripenem for complicated intra-abdominal infections, complicated urinary tract infection, nosocomial pneumonia, and acute biliary tract infection. The meta-analysis was carried on by the statistical software of Review Manager, version 5.2. Results: Compared with empirical antimicrobial agents on overall treatment efficacy, doripenem was associated with similar clinical and microbiological treatment success rates (for the clinical evaluable population, odds ratio [OR] = 1.26, 95% confidence interval [CI] 0.93-1.69, p = 0.13; for clinical modified intent-to-treatment population, OR = 0.88, 95% CI 0.55-1.41, p = 0.60; for microbiology evaluable population, OR = 1.16, 95% CI 0.90-1.50, p = 0.26; for microbiological modified intent-to-treatment (m-mITT), OR = 0.98, 95% CI 0.81-1.20, p = 0.87). We compared incidence of adverse events and all-cause mortality to analyze treatment safety. The outcomes suggested that doripenem was similar to comparators in terms of incidence of adverse events and all-cause mortality on modified intent-to-treatment population (for incidence of AEs, OR = 1.10, 95% CI 0.90-1.35, p = 0.33; for all-cause mortality, OR = 1.08, 95% CI 0.77-1.51, p = 0.67). In nosocomial pneumonia and ventilator-associated pneumonia treatment, doripenem was not inferior to other antibacterial agents in terms of efficacy and safety. Conclusion: From this meta-analysis, we can conclude that doripenem is as valuable and well-tolerated than empirical antimicrobial agents for complicated intra-abdominal infections, complicated urinary tract infection, acute biliary tract infection and nosocomial pneumonia treatment. .
Asunto(s)
Humanos , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Carbapenémicos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Enfermedad Aguda , Antibacterianos/efectos adversos , Carbapenémicos/efectos adversos , Colangitis/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Asociada al Ventilador/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of this article is to compare the efficacy and safety of doripenem for bacterial infections. METHODS: We included six randomized clinical trials identified from PubMed and Embase up to July 31, 2014. The included trials compared efficacy and safety of doripenem for complicated intra-abdominal infections, complicated urinary tract infection, nosocomial pneumonia, and acute biliary tract infection. The meta-analysis was carried on by the statistical software of Review Manager, version 5.2. RESULTS: Compared with empirical antimicrobial agents on overall treatment efficacy, doripenem was associated with similar clinical and microbiological treatment success rates (for the clinical evaluable population, odds ratio [OR]=1.26, 95% confidence interval [CI] 0.93-1.69, p=0.13; for clinical modified intent-to-treatment population, OR=0.88, 95% CI 0.55-1.41, p=0.60; for microbiology evaluable population, OR=1.16, 95% CI 0.90-1.50, p=0.26; for microbiological modified intent-to-treatment (m-mITT), OR=0.98, 95% CI 0.81-1.20, p=0.87). We compared incidence of adverse events and all-cause mortality to analyze treatment safety. The outcomes suggested that doripenem was similar to comparators in terms of incidence of adverse events and all-cause mortality on modified intent-to-treatment population (for incidence of AEs, OR=1.10, 95% CI 0.90-1.35, p=0.33; for all-cause mortality, OR=1.08, 95% CI 0.77-1.51, p=0.67). In nosocomial pneumonia and ventilator-associated pneumonia treatment, doripenem was not inferior to other antibacterial agents in terms of efficacy and safety. CONCLUSION: From this meta-analysis, we can conclude that doripenem is as valuable and well-tolerated than empirical antimicrobial agents for complicated intra-abdominal infections, complicated urinary tract infection, acute biliary tract infection and nosocomial pneumonia treatment.