Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

Preferências no exercício físico em mulheres portuguesas sobreviventes de cancro da mama

Introdução – Os benefícios do exercício físico em sobreviventes de cancro da mama têm sido reportados; contudo, a sua prática permanece baixa, tornando importante o conhecimento dos fatores que promovam a motivação e adesão ao exercício nesta população. Objetivos – Identificar as preferências quanto à programação e aconselhamento do exercício físico de uma amostra da população de mulheres portuguesas sobreviventes de cancro da mama e averiguar a influência das variáveis demográficas e médicas nestas preferências. Método – Foi aplicado um questionário a uma amostra não probabilística sequencial de 26 mulheres sobreviventes de cancro da mama. Resultados – A amostra era maioritariamente constituída por mulheres entre os 45 e os 62 anos, casadas ou em união de facto, com ensino básico, empregadas e com Índice de Massa Corporal (IMC) > 24,4. Maioritariamente tinham realizado cirurgia radical há um mês ou mais, apresentavam estadio I do tumor, efetuavam quimioterapia como tratamento adjuvante e algumas realizavam classes de fisioterapia. A maioria das participantes demonstrava interesse em receber aconselhamento, sentia-se apta a participar num programa de exercício, preferia receber aconselhamento face-a-face no hospital e acompanhada por outros doentes oncológicos. O exercício deveria ser supervisionado e com intensidade moderada, sendo as caminhadas o tipo de exercício preferido. Não foi estatisticamente possível realizar a associação entre as variáveis demográficas e médicas e as preferências. Conclusão – Alguns resultados obtidos estão em concordância com estudos prévios; contudo, outros divergem destes. Os resultados obtidos podem fornecer informações importantes para a construção futura de programas de exercício para esta população. ABSTRACT - Introduction – The benefits of physical exercise in cancer survivors have been reported, although it’s practice remains low, becoming important the acknowledgement of the factors that promote the motivation and adhesion of physical exercise in this population. Objectives – To identify the preferences about programming and counseling of physical exercise inside a population-based sample of Portuguese women who have survived breast cancer. We also intend to investigate the influence of demographic and medical variables in those preferences. Method – A questionnaire was applied to a non-probabilistic sequential sample of 26 women that have survived breast cancer. Results – Our sample was mainly composed by women aged between 45 and 62, married or in a cohabitation state, with basic instruction, employed and with a Body Mass Index (BMI)> 24.4. Most of them have had radical mastectomy for at least one month, had the Stage I of the tumor, and had done chemotherapy as an adjuvant treatment and some of them were practicing post-surgery physical therapy. The majority of participants showed interest in receiving counseling, felt able to participate in an exercise program, preferred receiving face-to-face counseling, at the hospital and with other cancer patients. The exercise should be supervised and with a moderate intensity. Walking was their preferred choice of exercise. It was not statistically possible to establish the relationship between demographic and medical variables and those preferences. Conclusion – Some results are in agreement with previous studies; however, others diverge from these. The results obtained can provide important information for future construction of exercise programs for this population.

Desvio de posicionamento em radioterapia para patologias de cabeça e pescoço e próstata: revisão de literatura

Introdução – Numa era em que os tratamentos de Radioterapia Externa (RTE) exigem cada vez mais precisão, a utilização de imagem médica permitirá medir, quantificar e avaliar o impacto do erro provocado pela execução do tratamento ou pelos movimentos dos órgãos. Objetivo – Analisar os dados existentes na literatura acerca de desvios de posicionamento (DP) em patologias de cabeça e pescoço (CP) e próstata, medidos com Cone Beam Computed Tomography (CBCT) ou Electronic Portal Image Device (EPID). Metodologia – Para esta revisão da literatura foram pesquisados artigos recorrendo às bases de dados MEDLINE/PubMed e b-on. Foram incluídos artigos que reportassem DP em patologias CP e próstata medidos através de CBCT e EPID. Seguidamente foram aplicados critérios de validação, que permitiram a seleção dos estudos. Resultados – Após a análise de 35 artigos foram incluídos 13 estudos e validados 9 estudos. Para tumores CP, a média (μ) dos DP encontra-se entre 0,0 e 1,2mm, com um desvio padrão (σ) máximo de 1,3mm. Para patologias de próstata observa-se μDP compreendido entre 0,0 e 7,1mm, com σ máximo de 7,5mm. Discussão/Conclusão – Os DP em patologias CP são atribuídos, maioritariamente, aos efeitos secundários da RTE, como mucosite e dor, que afetam a deglutição e conduzem ao emagrecimento, contribuindo para a instabilidade da posição do doente durante o tratamento, aumentando as incertezas de posicionamento. Os movimentos da próstata devem-se principalmente às variações de preenchimento vesical, retal e gás intestinal. O desconhecimento dos DP afeta negativamente a precisão da RTE. É importante detetá-los e quantificá-los para calcular margens adequadas e a magnitude dos erros, aumentando a precisão da administração de RTE, incluindo o aumento da segurança do doente. - ABSTRACT - Background and Purpose – In an era where precision is an increasing necessity in external radiotherapy (RT), modern medical imaging techniques provide means for measuring, quantifying and evaluating the impact of treatment execution and movement error. The aim of this paper is to review the current literature on the quantification of setup deviations (SD) in patients with head and neck (H&N) or prostate tumors, using Cone Beam Computed Tomography (CBCT) or Electronic Portal Image Device (EPID). Methods – According to the study protocol, MEDLINE/PubMed and b-on databases were searched for trials, which were analyzed using selection criteria based on the quality of the articles. Results – After assessment of 35 papers, 13 studies were included in this analysis and nine were authenticated (6 for prostate and 3 for H&N tumors). The SD in the treatment of H&N cancer patients is in the interval of 0.1 to 1.2mm, whereas in prostate cancer this interval is 0.0 to 7.1mm. Discussion – The reproducibility of patient positioning is the biggest barrier for higher precision in RT, which is affected by geometrical uncertainty, positioning errors and inter or intra-fraction organ movement. There are random and systematic errors associated to patient positioning, introduced since the treatment planning phase or through physiological organ movement. Conclusion – The H&N SD are mostly assigned to the Radiotherapy adverse effects, like mucositis and pain, which affect swallowing and decrease secretions, contributing for the instability of patient positioning during RT treatment and increasing positioning uncertainties. Prostate motion is mainly related to the variation in bladder and rectal filling. Ignoring SD affects negatively the accuracy of RT. Therefore, detection and quantification of SD is crucial in order to calculate appropriate margins, the magnitude of error and to improve accuracy in RTE and patient safety.

Avaliação da distribuição de dose no CTV-PTV através de imagem guiada em doentes com carcinoma da próstata

Mestrado em Radioterapia.

Implementation of proton therapy in the portuguese context of radiotherapy

Cancer is a national and international health care concern. It’s important to find strategies for early diagnosis as well as for the optimization of the various therapeutic options currently existing in Portugal. Cancer is the second leading cause of death in Portugal, the choice of this study, is due to the importance of radiotherapy approach in cancer treatment and because is the therapy used in 40% of oncology patients. Radiation therapy has evolve data technological level, that allows new treatment techniques that are more efficient and that also promotes greater professional satisfaction. The hadrons are charged particles, used in cancer therapy. These particles can bring a paradigm shift regarding the therapeutic approach in radiotherapy. The technique used is proton therapy, that reveal to be more accurate, efficacious and less toxic to surrounding tissue. Proton therapy may be a promising development in the field of oncology and how the treatment is given in radiotherapy. Although there is awareness of the benefits of proton therapy in oncology it’s also important to take in consideration the costs of these therapy, because they are considerably higher than conventional treatments of radiotherapy. Given the lack of a proton therapy service in Portugal, this study aims to be a documentary analysis of clinical records that will achieve the following objectives: to identify the number of cancer patients diagnosed in 2010 in Portugal and to calculate the estimated number of patients that could have been treated with proton therapy according to the Health Council of the Netherlands registration document.

A doença oncológica no fórum da História: breve síntese sobre a evolução da luta anticancerosa em Portugal

Introdução – A doença oncológica tem sido assunto de abordagem historiográfica particularmente abundante no contexto internacional. No caso português só recentemente começaram a surgir os primeiros trabalhos em redor desta ampla temática. Objetivos – Revolvendo em torno da emergência e estruturação da luta anticancerosa no âmbito internacional, pretende-se apresentar uma breve síntese sobre a evolução deste fenómeno em Portugal na primeira metade do século XX. Metodologia – Análise documental. Qualitativa e heurística. Resultados/Discussão/Considerações finais – A luta contra a doença oncológica em Portugal não destoou do contexto médico-científico e do movimento internacional anticanceroso da primeira metade do século XX. No entanto, a emergência e a institucionalização do projeto anticanceroso nacional apresentou algumas particularidades. Inserido entre uma especialidade médica em processo de afirmação e as necessidades assistenciais dos cancerosos, resultou da conjugação de uma série de fatores que ultrapassam a mera assimilação de novas tecnologias médicas ou da criação de um espaço próprio para a prática da oncologia. Tornou-se também num meio para realizar um trabalho intenso de educação para a saúde, num instrumento de ponta na formação médica especializada e numa referência de modernidade científica no contexto do Estado Novo.

Modelo de data mining para detecção de tumores em exames de rastreio

Dissertação para obtenção do grau de Mestre em Engenharia Informática

Contributo da radioterapia na melhoria dos cuidados de saúde no Centro Nacional de Oncologia - Luanda

Mestrado em Radiações Aplicadas às Tecnologias da Saúde - Área de especialização: Terapia com Radiações

Avaliação da distribuição de dose em doentes com cancro da mama: cobertura e homogeneidade no volume alvo e dose nos órgãos de risco

Mestrado em Radioterapia

A implementação de prototerapia no contexto da radioterapia em Portugal

Mestrado em Radioterapia - Área de especialização: Dosimetria Clínica

Tomografia por emissão de positrões: construção de uma guideline de atendimento

Mestrado em Medicina Nuclear - Área de especialização: Tomografia por emissão de positrões