STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect

<p>Abstract</p> <p>Background</p> <p>The Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributing to the tumourigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism with potential implication in the Warburg effect.</p> <p>Methods</p> <p>We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumour xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT) and knockdown (KD) untreated or irradiated (IR) tumours. Transcriptional profiling was based on Affymetrix Human GeneChip^®Gene 1.0 ST microarrays. Proteomes were determined from the tandem mass spectrometry (MS/MS) data by searching against the human subset of the UniProt database. Data were analysed using Significance Analysis of Microarrays for ribonucleic acid and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis with statistical significance measured by Fisher's exact test.</p> <p>Results</p> <p>Knockdown of STAT1 led to significant growth suppression in untreated tumours and radio sensitization of irradiated tumours. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis/gluconeogenesis (GG), the citrate cycle (CC) and oxidative phosphorylation (OP). Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumour-specific glycolysis. In addition, IR drastically suppressed the GG pathway in STAT1 KD tumours without significant change in STAT1 WT tumours.</p> <p>Conclusion</p> <p>Our results identify a previously uncharacterized function of STAT1 in tumours: expressional regulation of genes encoding proteins involved in glycolysis, the citrate cycle and mitochondrial oxidative phosphorylation, with predominant regulation of glycolytic genes. STAT1-dependent expressional regulation of glycolysis suggests a potential role for STAT1 as a transcriptional modulator of genes responsible for the Warburg effect.</p

Rapid Health and Needs assessments after disasters: a systematic review

<p>Abstract</p> <p>Background</p> <p>Publichealth care providers, stakeholders and policy makers request a rapid insight into health status and needs of the affected population after disasters. To our knowledge, there is no standardized rapid assessment tool for European countries. The aim of this article is to describe existing tools used internationally and analyze them for the development of a workable rapid assessment.</p> <p>Methods</p> <p>A review was conducted, including original studies concerning a rapid health and/or needs assessment. The studies used were published between 1980 and 2009. The electronic databasesof Medline, Embase, SciSearch and Psychinfo were used.</p> <p>Results</p> <p>Thirty-three studies were included for this review. The majority of the studies was of US origin and in most cases related to natural disasters, especially concerning the weather. In eighteen studies an assessment was conducted using a structured questionnaire, eleven studies used registries and four used both methods. Questionnaires were primarily used to asses the health needs, while data records were used to assess the health status of disaster victims.</p> <p>Conclusions</p> <p>Methods most commonly used were face to face interviews and data extracted from existing registries. Ideally, a rapid assessment tool is needed which does not add to the burden of disaster victims. In this perspective, the use of existing medical registries in combination with a brief questionnaire in the aftermath of disasters is the most promising. Since there is an increasing need for such a tool this approach needs further examination.</p