MicroRNA Expression and Regulation in Human Ovarian Carcinoma Cells by Luteinizing Hormone

MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH) contributions to LH receptor (LHR)-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR.Human ovarian cancer cells (SKOV3) were chosen as negative control (LHR-) and stably transfected to express functional LHR (LHR+), followed by incubation with LH (0-20 h). At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™), which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs.In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs.The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles

A simple and reproducible scoring system for EGFR in colorectal cancer: application to prognosis and prediction of response to preoperative brachytherapy

The aim of this study was to determine the predictive and prognostic value of epidermal growth factor receptor (EGFR) expression in rectal cancers treated with preoperative high-dose rate brachytherapy and in mismatch-repair (MMR)-proficient colorectal cancers (CRCs), respectively. We validate the use of receiver operating characteristic (ROC) curve analysis to select cutoff scores for EGFR overexpression for the end points studied. Immunohistochemistry (IHC) for EGFR was performed on 82 rectal tumour biopsies and 1197 MMR-proficient CRCs using a tissue microarray. Immunoreactivity was scored as the percentage of positive tumour cells by three pathologists and the inter-observer reliability was assessed. ROC curve-derived cutoffs were used to analyse the association of EGFR overexpression, tumour response and several clinicopathological features including survival. The scoring method was found to be reproducible in rectal cancer biopsies and CRCs. The selected cutoff scores from ROC curve analysis for each clinicopathological feature were highly consistent among pathologists. EGFR overexpression was associated with response to radiotherapy (P-value <0.001) and with worse survival time (P-value <0.001). In multivariate analysis, EGFR overexpression was independently associated with adverse prognosis (P-value <0.001). Epidermal growth factor receptor is a predictive marker of response to preoperative radiotherapy and an independent adverse prognostic factor CRC

Array-CGH and breast cancer

The introduction of comparative genomic hybridization (CGH) in 1992 opened new avenues in genomic investigation; in particular, it advanced analysis of solid tumours, including breast cancer, because it obviated the need to culture cells before their chromosomes could be analyzed. The current generation of CGH analysis uses ordered arrays of genomic DNA sequences and is therefore referred to as array-CGH or matrix-CGH. It was introduced in 1998, and further increased the potential of CGH to provide insight into the fundamental processes of chromosomal instability and cancer. This review provides a critical evaluation of the data published on array-CGH and breast cancer, and discusses some of its expected future value and developments

European scenario studies on future in-stream nutrient concentrations

Large-scale water quality issues have recently become the focus of policy and research. To gain insight into large-scale water quality issues, a scenario analysis was carried out for Europe using the continental water quality model WorldQual with total nitrogen and phosphorus as example pollutants. Future nitrogen and phosphorus loadings and instream concentrations were simulated for an “economy first” scenario and compared to contemporary conditions. Results indicate that future total nitrogen (TN) loadings are likely to decrease in most parts of central Europe by 5 to 25 kg ha-1 year-1 due to land-use change in the form of reduced cropland area as a result of technological changes, as well as improvements in land-use management based on higher efficiencies of application rates. Climate change has less impact on TN loadings, but an increase of future in-stream concentrations is accompanied by reduced river discharge. Future total phosphorus (TP) loadings are similar to contemporary loadings for all of Europe. In-stream TP concentrations do not change in northern and eastern Europe. In central Europe, concentrations increase little (by one class). In a few regions,such as northern Spain, very high changes (up to more than three classes) are apparent as a result of reduced river discharge

Envisioning the future of water in Europe - the SCENES project

The aim of this article is to describe the background and main elements of the SCENES project (Water Scenarios for Europe and Neighbouring States) together with the approach for selecting, constructing and evaluating water scenarios up to 2050. SCENES is a multi-faceted integrated project that aims to address the complex questions about the future of Europe’s water resources. It takes an integrated approach by combining and balancing the many dimensions of Europe’s water futures, including hydrological, ecological, economic, cultural, social, climatic, financial and other dimensions. The project is implemented in three phases. In the first phase (fast-track) largely extant scenarios are selected, and readily available information on drivers and policies information assembled and run through an existing quantitative model of pan-European water availability. In the second phase more refined scenarios are developed at both the pan-European and regional scales, with scenario panels providing ‘enriched’ scenarios. The third phase involves a synthesis of the information and dissemination of the project outputs to external stakeholders and end-users. In the SCENES project an evaluation of the participatory scenario processes is carried out giving us new information on the functioning of the science-policy interface, and on the challenges the European water management may confront in the future

Combining participative backcasting and exploratory scenario development: Experiences from the SCENES project

Social, natural and cultural systems are changing rapidly, influencing the future of Europe's fresh waters. One of the drivers shaping this future is the implementation of the Water Framework Directive. Participatory scenario development is well-suited to the challenges posed by the WFD to develop a long-term view by involving stakeholders. In this paper we analyse the process and results of a series of stakeholder workshops to develop scenarios at pan-European level. Specifically, we aim at analysing the method and results of combining a backcasting methodology and exploratory scenario development process. Four exploratory scenarios (narrative storylines) were developed, in first instance based on a set of existing European scenarios. Results matched expectations; the process produced stories that are complex, integrated, and rich in detail. During the backcasting exercise, four timelines were constructed, each of which took one exploratory scenario as context. The backcasting process established a strong link with the exploratory scenarios by identifying a large number of obstacles and opportunities in the realisation of those timelines. An analysis across all backcasts yielded a list of 15 robust elements, i.e. elements that are potentially effective in all exploratory scenarios. A stakeholder questionnaire showed that overall there was a widespread satisfaction with both the process and the results. Stakeholders were satisfied with the overall methodology and the exploratory scenarios and somewhat more critical on the backcasting exercise and resulting robust strategies. Above all, we hope to have demonstrated that it is conceptually appealing, methodologically feasible, and practically useful to combine exploratory scenario development and backcasting analysis