Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

Background: Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results: The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ¿5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion: The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy.

Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

Background: Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results: The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ¿5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion: The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy.

Destination image of Girona: an online text-mining approach

The main objective of this Master Thesis is to discover more about Girona’s image as a tourism destination from different agents’ perspective and to study its differences on promotion or opinions. In order to meet this objective, three components of Girona’s destination image will be studied: attribute-based component, the holistic component, and the affective component. It is true that a lot of research has been done about tourism destination image, but it is less when we are talking about the destination of Girona. Some studies have already focused on Girona as a tourist destination, but they used a different type of sample and different methodological steps. This study is new among destination studies in the sense that it is based only on textual online data and it follows a methodology based on text-miming. Text-mining is a kind of methodology that allows people extract relevant information from texts. Also, after this information is extracted by this methodology, some statistical multivariate analyses are done with the aim of discovering more about Girona’s tourism image

The use of mixed methods research in interdisciplinary educational journals

Mixed methods research is becoming increasingly important in several scientific areas. The analysis of prevalence rates is a new line of research that has emerged in mixed methods research, and this methodological approach has only been applied carefully in a handful of journals. The purpose of this article was to analyse the prevalence of mixed methods research in interdisciplinary educational journals. Moreover, the main characteristics of the mixed methods articles identified were examined. This study used a mixed methods approach to analyse these aspects. Specifically, a partially mixed sequential equal status multiple-case study design was applied with a development mixed methods purpose. Three educational journals in different disciplines were reviewed from 2005 to 2010 (Academy of Management Learning and Education, Educational Psychology Review, Journal of the Learning Sciences). The findings show differences among the journals in the prevalence rates and characteristics of the mixed methods studies