Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5aHigh). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma

Diagnostic and prognostic value of B4GALT1 hypermethylation and its clinical significance as a novel circulating cell-free DNA biomarker in colorectal cancer

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan-Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592-0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

<p>Abstract</p> <p>Background</p> <p>Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.</p> <p>Methods</p> <p>The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC.</p> <p>Results</p> <p>Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (<it>NDRG2) </it>promoter was found methylated in all CRC cell lines. <it>NDRG2 </it>hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated.</p> <p>Conclusion</p> <p>The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.</p

SIGRI project: Products validation results

The pilot project SIGRI (Sistema Integrato per la Gestione del Rischio Incendi) of the Italian Space Agency aims at developing an integrated system for the management of wildfires. The system provides satellite-based products capable of assisting in all phases of fire combat activities: forecast, detection, damage assessment, and recovery. The SIGRI goals were achieved by implementing consolidated methodologies, and/or developing innovative tools and methods for the automated analysis of multispectral, Synthetic Aperture Radar, and non-EO data. This paper focuses on the testing and validation of algorithms developed during the final phase of SIGRI. The validation of the products generated is an important phase in which their potential is assessed, and algorithms are calibrated. We discuss the results of the validation process of the main chain of unsupervised products: Modified Fire Probability Index by multispectral moderate resolution data (prevention), early detection of fire Hot Spots by multispectral very-high temporal resolution data (response), and identification and mapping of Burn Scars (damage assessment) by high-spatial resolution electro-optical and Synthetic Aperture Radar data

Remote Sensing water observation for supporting Lake Victoria weed management

This paper aims to assess the suitability of remote sensing for enhancing the management of water body resources and for providing an inexpensive way to gather, on a wide area, weed infestation extent and optical parameter linked to the water body status. Remotely sensed satellite images and ancillary ground true data were used to produce land cover maps, trough classification techniques, and water compounds maps, applying radiative transfer models. The study proposed within the framework of the cooperation between Italian Foreign Affair Ministry (through the University of Rome) and Kenyan Authorities has been carried out on the Kenyan part of the Lake Victoria. This lake is one of the largest freshwater bodies of the world where, over the last few years environmental challenges and human impact have perturbed the ecological balance affecting the biodiversity. The objective of this research study is to define the thematic products, retrievable from satellite images, like weed abundance maps and water compound concentrations. These products, if provided with an appropriate time frequency, are useful to identify the preconditions for the occurrence of hazard events like abnormal macrophyte proliferation and to develop an up-to-date decision support system devoted to an apprised territory, environment and resource management

COSMO SkyMed AO projects -multi-temporal SAR and optical data integrated approach for weed infested inland waters

In this paper we deal with the integrated use of time-series of SAR and MODIS images to derive the temporal behavior, the abundance and the distribution of the floating macrophytes in the Winam Gulf (Kenyan portion of the Lake Victoria). The proliferation of invasive plants and aquatic weeds is of growing concern. Starting from 1989, Lake Victoria has been interested by the highest infestation of water hyacinth with significant socio-economic impact on riparian populations. The information provided by satellite can play an important role in supporting a decision system for the management of the water resources allowing also an easy and inexpensive way of monitoring the environment response to any action that might be undertaken to contrast its degradation. This paper aims at assessing the capability of medium/high resolution (Wideregion and Stripmap) COSMO-SkyMed ScanSAR time series imagery to support/supplement optical data, frequently affected by clouds, in the knowledge of temporal macrophytes growing cycles and sustain the monitor and management of the Lake Victoria waters. © 2012 IEEE

ASSESSMENT OF THE ABNORMAL GROWTH OF FLOATING MACROPHYTES IN WINAM GULF (KENYA) BY USING MODIS IMAGERY TIME SERIES

The objective of this research study is to assess the capability of time-series of MODIS imagery to provide information suitable for enhancing the understanding of the temporal cycles shown by the abnormal growth of the floating macrophytes in order to support monitoring and management action of Lake Victoria water resources. The proliferation of invasive plants and aquatic weeds is of growing concern. Starting from 1989, Lake Victoria has been interested by the high infestation of water hyacinth with significant socio-economic impact on riparian populations. In this paper, we describe an approach based on the time-series of MODIS to derive the temporal behaviour, the abundance and distribution of the floating macrophytes in the Winam Gulf (Kenyan portion of the Lake Victoria) and its possible links to the concentrations of the main water constituencies. To this end, we consider the NDVI values computed from the MODIS imagery time-series from 2000 to 2009 to identify the floating macrophytes cover and an appropriate bio-optical model to retrieve, by means of an inverse procedure, the concentrations of chlorophyll a, coloured dissolved organic matter and total suspended solid. The maps of the floating vegetation based on the NDVI values allow us to assess the spatial and temporal dynamics of the weeds with high time resolution. A floating vegetation index (FVI) has been introduced for describing the weeds pollution level. The results of the analysis show a consistent temporal relation between the water constituent concentrations within the Winam Gulf and the FVI, especially in the proximity of the greatest proliferation of floating vegetation in the last 10 years that occurred between the second half of 2006 and the first half of 2007.The adopted approach will be useful to implement an automatic system for monitoring and predicting the floating macrophytes proliferation in Lake Victoria

Evaluating Hyperion capability for land cover mapping in a fragmented ecosystem: Pollino National Park, Italy

We analyze the capability of Hyperion spaceborne hyperspectral data for discriminating land cover in a complex natural ecosystem according to the structure of the currently used European standard classification system (CORINE Land Cover 2000). For this purpose, we used Hyperion imagery acquired over Pollino National Park (Italy). Hyperion pre-processed data (30 m spatial resolution) were classified at the pixel level using common parametric supervised classification methods. The algorithms' performance and class level accuracy were compared with those obtained for the same area using airborne hyperspectral MIVIS data (7 m spatial resolution). Moreover, in selected test areas characterized by heterogeneous land cover (as mapped by MIVIS classification) a Linear Spectral Unmixing (LSU) technique was applied to Hyperion data to derive the abundance fractions of land cover endmembers. The accuracy of the LSU analysis was evaluated using the Residual Error parameter, by comparing Hyperion LSU results with land cover fractional abundances achieved from reference data (i.e., MIVIS and air-photo classification). The results show the potential of Hyperion spaceborne hyperspectral imagery in mapping land cover and vegetation diversity up to the 4th level of the CORINE legend, even at the sub-pixel level, within a fragmented ecosystem such as that of Pollino National Park. Moreover, we defined a criterion for evaluating the Hyperion accuracy in retrieving land cover abundances at the sub-pixel scale. Sub-pixel analysis allowed us to determine the optimal threshold to select the areas on which consistent fractional land cover monitoring can be achieved using the Hyperion sensor. (c) 2008 Elsevier Inc. All rights reserved