Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells

Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.

Estudo e conceção de um sistema de encaixe rápido e simples para próteses de membros inferiores

Dissertação de mestrado integrado em Engenharia Biomédica

Modelação de governo electrónico para países emergentes: O caso de São Tomé e Príncipe

Tese de Doutoramento em Tecnologias e Sistemas de Informação

O ensino da flauta de bisel em grupo como inovação pedagógica: Uma investigação-ação no 2.º Ciclo do Ensino Básico

Tese de Doutoramento em Estudos da Criança (Especialidade em Educação Musical)

Análise de sustentabilidade de soluções construtivas inovadoras para a reabilitação de edifícios antigos

Dissertação de mestrado integrado em Engenharia Civil

Algorithms and computational tools for metabolic flux analysis

PhD thesis in Biomedical Engineering

Modelling and verifying smell-free architectures with the Archery language

Architectural (bad) smells are design decisions found in software architectures that degrade the ability of systems to evolve. This paper presents an approach to verify that a software architecture is smellfree using the Archery architectural description language. The language provides a core for modelling software architectures and an extension for specifying constraints. The approach consists in precisely specifying architectural smells as constraints, and then verifying that software architectures do not satisfy any of them. The constraint language is based on a propositional modal logic with recursion that includes: a converse operator for relations among architectural concepts, graded modalities for describing the cardinality in such relations, and nominals referencing architectural elements. Four architectural smells illustrate the approach.

Reprogramming energy metabolism and inducing angiogenesis : co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas.

Identificação do tipo e quantidade de PCM adequado ao clima Português

Dissertação de mestrado integrado em Engenharia Civil

Basic constraints between two vectors

This chapter deals with the characterization of the basic constraints between two vectors. This issue plays a crucial role in the formulation of constraint equations for mechanical joints. In particular, relations between two parallel and two perpendicular vectors are derived. Moreover, formulation for a vector that connects two generic points is presented. The material described here is developed under the framework of multibody systems formulation for spatial systems.

Kinematic joints constraints

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Equations of motion for constrained systems

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.

Da previsibilidade da notícia às vantagens da agenda jornalística: uma reflexão a partir do Rádio Clube Português

Dissertação de mestrado em Ciências da Comunicação (área de especialização em Informação e Jornalismo)

Multibody systems formulation

"Series: Solid mechanics and its applications, vol. 226"