RESUMEN
BACKGROUND: Inhibition of tumor-induced angiogenesis may restrict tumor growth and metastasis. Long-term systemic delivery of angiogenic inhibitors is associated with toxicity, as well as other severe side-effects. The utility of cells as vehicles for gene therapy to deliver therapeutic molecules has been suggested to represent an efficient approach. Mesenchymal stem cells (MSCs) exhibit a tropism to cancer tissue, and may serve as a cellular delivery vehicle and a local producer of anti-angiogenic agents. METHODS: In the present study, we attempted to assess production of the transgene, α1-antitrypsin (AAT), in lentivirus-transduced human MSCs and its cytotoxicity against human umbilical cord vein endothelial cells (HUVEC). The secreted protein from these effector cells was determined by an enzyme-linked immunosorbent assay. The cytotoxicity of hMSCs that overexpress the human AAT gene against HUVEC was evaluated with an apoptotic assay. RESULTS: Lentivirus-transduced hMSCs produced functional AAT and displayed much higher cytotoxicity against HUVEC than untransduced hMSCs. Moreover, AAT secreted from transduced hMSCs significantly inhibited HUVEC proliferation compared to untransduced hMSCs. The data obtained demonstrate for the first time that genetically modified hMSCs released abundant and functional AAT that caused obvious cytotoxicity to HUVEC. CONCLUSIONS: hMSC may serve as an effective platform for the targeted delivery of therapeutic proteins to cancer sites.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Células Endoteliales/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Inhibidores de Tripsina/genética , alfa 1-Antitripsina/genética , Inhibidores de la Angiogénesis/genética , Inhibidores de la Angiogénesis/metabolismo , Apoptosis/efectos de los fármacos , Células de la Médula Ósea , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Lentivirus/genética , Células Madre Mesenquimatosas/citología , Elastasa Pancreática/antagonistas & inhibidores , Fenotipo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Transducción Genética , Transgenes/genética , Inhibidores de Tripsina/metabolismo , Inhibidores de Tripsina/farmacología , Venas Umbilicales , alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/farmacologíaRESUMEN
BACKGROUND: The World Health Organization Quality of Life Questionnaire (WHOQOL)-BREF is one of the most known general questionnaires for assessment of quality of life (QOL) in both healthy populations and in various diseases subgroups. The aim of the present study was to examine the construct validity of this questionnaire in patients with coronary artery disease (CAD) using factor analysis. METHODS: Two hundred and seventy-five patients aged 35-80 years old with the diagnosis of CAD admitted to the Tehran Heart Center operating room for coronary artery bypass were consecutively entered into the study. QOL was assessed using the WHOQOL-BREF. To estimate the reliability of the QOL questionnaire, Cronbach's a coefficient was measured. To assess the structure of the questionnaire, we firstly performed confirmatory factor analysis to test the hypothesized factor models. Exploratory factor analysis was then performed using the principal component method with varimax rotation. RESULTS: Reliability of the questionnaire was low (Cronbach's a for different domains ranged from 0.24 to 0.74). In confirmatory factor analysis, only the 1-factor model indicated a good fit to the data. The exploratory factor analysis indicated a five-factor solution that jointly accounted for 55.7% of the variance observed. Also, the pattern of item loading was very different from the original structure of the questionnaire. CONCLUSIONS: The findings suggest that the WHOQOL-BREF might only be a measure of the overall QOL in patients with CAD, and is not a suitable instrument for measuring the different QOL dimensions as expected in this population.