RESUMO
High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Serpinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Ácido Ascórbico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Antineoplásicos/uso terapêutico , Serpinas/genética , Inibidor 1 de Ativador de Plasminogênio/genéticaRESUMO
OBJECTIVES: The aims of this study were to explore the Pittsburgh Sleep Quality Index (PSQI) and health service utilization in Chinese general population, to investigate the association between PSQI and health service utilization and to identify the independent contributions of social demographic variables, health related factors and PSQI to health service utilization. METHODS: In a cross-sectional community-based health survey using a multi-instrument questionnaire, 4067 subjects (≥15 years old) were studied. The Chinese version of the PSQI was used to assess sleep quality. Health service utilization was measured by recent two-week physician visit and annual hospitalization rates. RESULTS: Higher PSQI scores were associated with more frequent health service utilization. Higher scores in subjective sleep quality were associated with higher rate of recent two-week physician visit (adjusted OR = 1.24 per SD increase, P = 0.015). Higher scores in habitual sleep efficiency (adjusted OR = 1.24 per SD increase, P = 0.038) and sleep disturbances (adjusted OR = 2.09 per SD increase, P < 0.001) were associated with more frequent annual hospitalization. The independent influence of PSQI on the risk of recent two-week physician visit was 0.7%, and that of annual hospitalization 31.4%. CONCLUSIONS: Poorer sleep quality predicted more frequent health service utilization. The independent contribution of PSQI on health service utilization was smaller than social demographic variables.
Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Sono , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Análise por Conglomerados , Estudos Transversais , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Distúrbios do Início e da Manutenção do Sono/terapia , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
The aim of the present study was to investigate the inhibitory effects of dihydroartemisinin (DHA) on the primary tumor growth and metastasis of the human breast cancer cell line, MDA-MB-231, in vitro. The expression levels of urokinase-type plasminogen activator (uPA) were detected by immunocytochemistry in two cell lines (MCF-7 and MDA-MB-231). The MDA-MB-231 cell activity was inhibited by various concentration gradients of DHA. The inhibitory rate, cell growth curve and apoptotic morphological observations were obtained using the MTT assay at 0, 24, 48 and 72 h. Cell scratch migration was performed at various time-points to test the cell proliferation and migration capacity. Reverse transcription-polymerase chain reaction was used to analyze the effect of DHA on uPA mRNA expression in breast cancer cells. The human breast cancer cell line, MDA-MB-231, possesses higher metastatic potential and relatively higher expression of uPA when compared with the MCF-7 cell line. DHA was found to inhibit the proliferation and migration capacity of the cell line, MDA-MB-231, in vitro. The growth inhibition occurred in a time- and dose-dependent manner, with IC50 values of 117.76±0.04, 60.26±0.12 and 52.96±0.07 µmol/l following 24, 48 and 72 h, respectively. The inhibition of uPA was observed to decrease breast cancer cell growth and migration. Thus, results of the present study indicate that DHA may be used for further studies with regard to breast cancer therapy.