ABSTRACT
Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133(+)) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133(+) cells were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133(+) cells were significantly higher than those in CD133(-) cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133(+) and CD133(-) cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133(+) A549 cells were considerably lower than those of CD133(-) A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/biosynthesis , Biomarkers, Tumor/biosynthesis , Carcinoma, Non-Small-Cell Lung/genetics , Radiation Tolerance/genetics , AC133 Antigen , Antigens, CD/genetics , Apoptosis/radiation effects , Basic Helix-Loop-Helix Transcription Factors/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Cell Line, Tumor , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , Humans , Male , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/radiation effects , Peptides/genetics , PrognosisABSTRACT
OBJECTIVE: To assess the effect of intensive insulin therapy on outcomes of patients with severe acute pancreatitis. METHODS: Relevant literatures cited in these electronic databases: Medline, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNK1) database, and Excerpta Medical database (Embase) were systematically searched for randomized controlled trials (RCTs) in which intensive insulin therapy was used in severe acute pancreatitis. Length of hospitalization, acute physiology and chronic health evaluation II (APACHE II) score, incidence of complications, and adverse effects were recorded for statistical analysis. The methodological quality of the eligible studies was assessed by Jadad scale. The results were analysed by Revman 4.3 software. RESULTS: Three studies, which included a total of 118 cases, were finally reviewed. The methodological quality of the trials varied substantially In patients with severe acute pancreatitis, intensive insulin therapy was associated with shorter length of hospitalization (weighted mean difference (WMD) = -12.13, 95% confidence interval (CI) [-15.48, 8.78], p > 0.00001) and lower APACHE II score after 72 hours treatment (WMD = -3.80, 95% CI [-4.88,2. 72], p > 0.00001). One study reported insulin-related adverse event. CONCLUSION: In patients with severe acute pancreatitis, intensive insulin therapy could relieve the patient's condition earlier and shorten the length of hospitalization without serious adverse effect.
