Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics

Glioma-associated stem cells: A novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma

Diffuse Low-Grade Gliomas in Adults

Numerous diagnostic, prognostic, and therapeutic issues concerning lowgrade gliomas still remain to be clari fi ed. In this regard, in vitro and in vivo models of low-grade gliomas would represent a way to get insight into these crucial aspects. However, many of the in vitro and in vivo models assayed in the literature are focused on high-grade gliomas. For this reason, in this chapter we reviewed the literature on low-grade glioma culture describing the results so far obtained, highlighting limitations and envisioning promising innovative directions that research is undertaking in this critical fi eld. Speci fi cally, fi rst, we critically presented the conventional methods adopted to study low-grade gliomas, such as continuous human tumor cell lines and short-term glioma cultures. Then, we discussed the culture methods utilized to isolate and in vitro expand glioma cancer stem cells from adult and pediatric tumors, underlining the need of optimizing new culture conditions because of the partial failure of the simple transfer to low-grade gliomas of the methods ef fi cient in isolating glioma stem cells from highgrade gliomas. Finally, we presented the innovative, although still in its infancy, possibility to culture nonneoplastic stromal cells as a way to obtain cell lines representative of the biological behavior of the patient tumors. In conclusion, the aim of this chapter was to explain why the culture of patient-derived cancer cells represents a unique opportunity to create in vitro and in vivo models closely mimicking the biological properties of the patient tumor, thus allowing a patient-based approach

A balanced scorecard-based model for evaluating e-learning and conventional pedagogical activities in nursing

The evaluation of e-learning and conventional pedagogical activities in nursing programmes has focused either on a single pedagogical activity or the entire curriculum, and only on students or teachers\u27 perspective. The goal of this study was to design and test a novel approach for evaluation of e-learning and conventional pedagogical activities that considers students\u27, teachers\u27 and managers\u27 perspectives. A case study of the proposed approach was performed at a publicly funded nursing faculty with Slovenian and Italian students from 2009 to 2012. The case study was combined with focus group discussions, interviews, direct observation and survey. The proposed approach allows management to compare the value of different pedagogical activities through the students\u27, teachers\u27 and managers\u27 perspectives. The approach proved useful in the evaluation of pedagogical activities and provided valid arguments for long-term pedagogical process improvemen

Glioma-Associated Stem Cells: A Novel Class of Tumor-Supporting Cells Able to Predict Prognosis of Human Low-Grade Gliomas

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239-125

The EUPPBench postprocessing benchmark dataset v1.0

Abstract. Statistical Postprocessing of medium-range weather forecasts is an important component of modern forecasting systems. Since the beginning of modern data science, numerous new postprocessing methods have been proposed, complementing an already very diverse field. However, one of the questions that frequently arises when considering different methods in the framework of implementing operational postprocessing is the relative performance of the methods for a given specific task. It is particularly challenging to find or construct a common comprehensive dataset that can be used to perform such comparisons. Here, we introduce the first version of EUPPBench, a dataset of time-aligned forecasts and observations, with the aim to facilitate and standardize this process. This dataset is publicly available at https://github.com/EUPP-benchmark/climetlab-eumetnet-postprocessing-benchmark. We provide examples on how to download and use the data, propose a set of evaluation methods, and perform a first benchmark of several methods for the correction of 2-meter temperature forecasts. </jats:p