Fluvastatin-mediated down-regulation of SATB1 affects aggressive phenotypes of human non-small-cell lung cancer cell line H292.

AIMS: Fluvastatin reduces tumor proliferation and increased apoptotic activity in various cancers. Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that reprogrammes the gene transcription profiles of tumors to promote growth and metastasis. The antitumor effect and molecular mechanisms of fluvastatin on lung cancer is poorly understood. This study aimed to investigate the antitumor effect of fluvastatin on lung cancer and its possible mechanics. MAIN METHODS: Cell viability assay was used to examine the inhibition of fluvastatin on proliferation of H292 cells. In order to investigate the antitumor mechanics, SATB1 knock-down H292 cells was constructed by lentiviral transfection. RT-PCR and Western blot were performed to examine the effects of fluvastatin on expression of SATB1 and Wnt/ß-catenin signaling components. KEY FINDINGS: Fluvastatin significantly inhibited proliferation and invasion of H292 cells in a time- and dose-dependent manner and promoted the apoptosis (p < 0.05). The expression of SATB1 was down-regulated by fluvastatin in a dose-dependent manner. The proliferation and invasion of SATB1-shRNA cells was significantly suppressed, and the apoptosis was significantly enhanced (p < 0.05). We also show that the common target genes were regulated by SATB1 and Wnt/ß-catenin pathway simultaneously. There may be a functional link between SATB1 and Wnt/ß-catenin pathway. SIGNIFICANCE: We presented a possible mechanism of statins that fluvastatin significantly suppressed the in vitro tumor progression of H292 cells possibly by down-regulation of SATB1 via Wnt/ß-catenin pathway, which provided new therapeutic possibilities for more cancers driven by hyperexpression of SATB1 and Wnt/ß-catenin pathway.

Prognostic role of hypoxic inducible factor expression in non-small cell lung cancer: a meta-analysis.

INTRODUCTION: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. METHODS: PubMed were used to identify relevant literature with the last report up to December 20th, 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. RESULTS: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-1α and three for HIF-2α. Combined HRs suggested that higher expression of HIF1α had a negative impact on NSCLC patient survival (HR=1.50; 95%CI =1.07-2.10; p=0.019). The expression of HIF-2α was also relative to a poorer survival (HR=2.02; 95%CI =1.47-2.77; p=0.000). No bias existed in either of the two groups. CONCLUSION: This study suggests that elevations of HIF-1α and HIF- 2α expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC.

Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: experimental and clinical evidence.

PURPOSE: This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT). METHODS: Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100-150 mm(3). On planned days, tumors were measured for cell apoptosis, microvessel density, pericytes, blood-vessel morphology, and tumor hypoxia. The tumor response under different combinations of rh-Endo and RT schedules was evaluated. RESULTS: Tumor hypoxia was significantly reduced 5 days after rh-Endo in NSCLC patients, and a similar result was found in the LLC mouse model. The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared to any other treatment schedule. rh-Endo treatment remodeled the tumor vasculature after 5 days by reducing microvessel density and increasing pericytic coverage of the vessel endothelium. CONCLUSION: This study demonstrated decreased hypoxia in animals and patients upon rh-Endo treatment, which also enhanced the radioresponse within the vasculature-remodeling period. The optimal clinical combination of rh-Endo and RT warrants further investigation.

Insufficient screening knowledge in Chinese interns: a survey in ten leading medical schools.

OBJECTIVE: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening. METHODS: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire. RESULTS: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge. CONCLUSION: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.