Logic programming and artificial neural networks in breast cancer detection

About 90% of breast cancers do not cause or are capable of producing death if detected at an early stage and treated properly. Indeed, it is still not known a specific cause for the illness. It may be not only a beginning, but also a set of associations that will determine the onset of the disease. Undeniably, there are some factors that seem to be associated with the boosted risk of the malady. Pondering the present study, different breast cancer risk assessment models where considered. It is our intention to develop a hybrid decision support system under a formal framework based on Logic Programming for knowledge representation and reasoning, complemented with an approach to computing centered on Artificial Neural Networks, to evaluate the risk of developing breast cancer and the respective Degree-of-Confidence that one has on such a happening.

Crianças referenciadas e em residências de acolhimento no distrito de Braga: risco familiar

Pela repercussão de determinadas famílias serem estigmatizadas, considerando-se “disfuncionais” ou “desestruturadas” (Furniss, 1991; Marvasti, 1995), tivemos como objetivos favorecer a identificação de fatores socioculturais (e de estrutura familiar) e discriminar indicadores de mal-estar e risco familiar. Com uma metologia qualitativa, num contexto de investigação-ação (Bryman, 2008; Denzin & Lincoln, 2005), junto de crianças referenciadas para acolhimento institucional foi utilizado por estudantes de ensino superior um guião, para entrevistas individuais, face a face e semiestrutruradas (Harrison, Geddens, & Sharpe, 2006). Selecionamos para a amostra crianças a viverem em Centros de Acolhimento Temporário (CAT), incluindo-se 7 do sexo feminino e 7 do sexo masculino. Para análise dos dados recolhidos recorremos a metodologias visuais e de análise de discurso (Rose, 2005). Os resultados permitiram-nos identificar crises familiares graves e outras mudanças aludidas constatando-se ser desenhada a “pessoa especial” e uma família (Corman, 1967; Font, 1978). Os diálogos sobre as circunstâncias e atividades do quotidiano, revelaram que o insucesso escolar é uma manifestação de preocupação de quem tenta incentivar os mais novos na procura de amizades, na construção de uma maior autonomia, estabelecendo-lhes limites de conduta e apoio na criação de objetivos e nos seus esforços para dominarem a agressividade.

Qualidade de vida, morbilidade psicológica e stress familiar em idosos residentes na comunidade

Este estudo procurou investigar as relações existentes entre morbilidade psicológica, stress familiar e qualidade de vida (QV) da pessoa idosa. A amostra foi constituída por 126 idosos. Os instrumentos utilizados foram: The Lawton Instrumental Activities of Daily Living (IADL), Quality of Life (WHOQOL-Bref), Geriatric Anxiety Inventory (GSI), Geriatric Depression Scale (GDS); e Index of Family Relations (IFR). Os resultados revelaram a importância da idade, estado civil, escolaridade e número de patologias assim como o género na capacidade funcional, morbilidade, stress familiar e QV. Ao nível dos preditores, a depressão foi a variável que mais contribuiu para a QV. Não foram encontradas variáveis moderadoras no modelo. A discussão e implicações dos resultados são abordadas bem como a intervenção psicológica nesta população.

Desenvolvimento e projeto de colhedora de babaçu (Orbignya phalerata Mart.) para agricultura familiar nas regiões de matas de transição da Amazônia

O babaçu (Orbignya phalerata) é uma típica palmeira das matas de transição dos ecossistemas Amazônia/Cerrado e Amazônia/Caatinga, sendo de grande importância econômica, social e ambiental nestas regiões. Os produtos advindos dos babaçuais possibilitam renda para uma das camadas mais pobres da região amazônica e um dos entraves para a obtenção eficiente destes produtos é a colheita dos cocos de babaçu, que atualmente se faz no sistema extrativista. O objetivo deste trabalho foi realizar o desenvolvimento e projeto de uma colhedora de babaçu adaptável ao ambiente de trabalho da agricultura familiar e as características das matas de transição amazônicas. Para tal foram realizados estudos de literatura que nortearam as decisões e simplificações de projeto, assim como foram realizados os cálculos e desenhos da nova colhedora. O projeto foi realizado através de ferramentas de engenharia que apresentaram como resultados o memorial de cálculo que descreve o caminho técnico para o dimensionamento dos elementos constituintes da colhedora e a partir destes os desenhos detalhados dos elementos da nova máquina. Pelos desenhos detalhados suas considerações e decisões concluí-se que a colhedora de babaçu apresenta-se passível de ser construída com materiais nacionais de baixo custo, além de fácil operação, manutenção e com mínimo efeito sobre os babaçuais naturais.

Localization of MCT2 at peroxisomes is associated with malignant transformation in prostate cancer

Previous studies on monocarboxylate transporters expression in prostate cancer (PCa) have shown that monocarboxylate transporter 2 (MCT2) was clearly overexpressed in prostate malignant glands, pointing it out as a putative biomarker for PCa. However, its localization and possible role in PCa cells remained unclear. In this study, we demonstrate that MCT2 localizes mainly at peroxisomes in PCa cells and is able to take advantage of the peroxisomal transport machinery by interacting with Pex19. We have also shown an increase in MCT2 expression from non-malignant to malignant cells that was directly correlated with its peroxisomal localization. Upon analysis of the expression of several peroxisomal ß-oxidation proteins in PIN lesions and PCa cells from a large variety of human prostate samples, we suggest that MCT2 presence at peroxisomes is related to an increase in ß -oxidation levels which may be crucial for malignant transformation. Our results present novel evidence that may not only contribute to the study of PCa development mechanisms but also pinpoint novel targets for cancer therapy.

Evolving hallmarks in urothelial bladder cancer: unveiling potential biomarkers

Urothelial bladder carcinoma (UBC), the most frequent type (90%) of bladder cancer and the second most common malignancy of the urogenital region, is a relatively well understood type of cancer, with numerous studies concerning pathogenetic pathways, natural history and bladder tumor biology being reported. Despite this, it continues to remain a challenge in the oncology field, mostly due to its relapsing and progressive nature, and to the heterogeneity in the response to cisplatin-containing regimens. Although the formulae based on clinical staging and histopathological parameters are classically used as diagnostic and prognostic tools, they have proven insufficient to characterize the individual biological features and clinical behaviour of the tumours. Understanding the pathobiology of the disease can add important information to these classical criteria, and contribute to accurately predict outcome and individualize therapy for UBC patients. In this line of investigation, we found that tumour angiogenesis and lymphangiogenesis, the process of invasion and metastasis and the energy metabolism reprogramming/tumour microenvironment encompass several potential biomarkers that seem to infl bladder cancer aggressiveness and chemoresistance. We particularly highlight the roles of lymphovascular invasion, and of RKIP, CD147 and MCT1 immunoexpressions, as relevant prognostic and/or predictive biomarkers, and as promising areas of therapeutic intervention, eliciting for the development of additional studies that can validate and further explore these biomarkers.

Urothelial bladder cancer progression: lessons learned from the bench

Urothelial bladder carcinoma (UBC) is an intricate malignancy with a variable natural history and clinical behavior. Despite developments in diagnosis/prognosis refinement and treatment modalities, the recurrence rate is high, and progression from non-muscle to muscle invasive UBC commonly leads to metastasis. Moreover, patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment, and overall survival rates are poor. Thus, UBC remains a challenge in the oncology field, representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence, progression, and chemo-refractoriness. However, progress toward personalized medicine has been hampered by the unique genetic complexity of UBC. Recent genome-wide expression and sequencing studies have brought new insights into its molecular features, pathogenesis and clinical diversity, revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups. Hence, it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation. In this review, we have summarized ours and others' research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer: tumor neovascularization, invasion and metastasis, and energy metabolism reprogramming of the tumor microenvironment.

Reclusão feminina e processos de reconfiguração familiar

FCT

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.

Exploring the role of O-Mannosylation in the modulation of E-Cadherin function in Gastric Cancer cell line models

Dissertação de mestrado em Bioquímica Aplicada – Biomedicina

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Acomodação familiar e criticismo percebido em pacientes com transtorno obsessivo-compulsivo

OBJETIVO: O transtorno obsessivo-compulsivo (TOC) causa importante impacto sobre a dinâmica familiar. Frequentemente, ocorrem modificações na rotina da família, a qual acaba se adaptando aos sintomas e às exigências do paciente, fenômeno denominado acomodação familiar. Portadores de TOC podem sentir-se, ainda, alvo de críticas por parte de pessoas de seu convívio. Alguns estudos associam pior prognóstico a maiores Índices de Acomodação Familiar e criticismo percebido. Este artigo tem como objetivo verificar possíveis associações entre tipos de sintomas predominantes (dimensões) determinados pela escala DYBOCS, em relação ao funcionamento familiar e percepção crítica dos pacientes. MÉTODO: Quarenta e nove pacientes e seus familiares foram avaliados por meio da aplicação de escalas para medição dos índices de criticismo percebido (Perceived Criticism Scale) e acomodação familiar (Family Accommodation Scale), além de escalas para medir a intensidade dos sintomas obsessivo-compulsivos (Dimensional Yale-Brown Obsessive-Compulsive Scale, Yale-Brown Obsessive-Compulsive Scale), depressivos e ansiosos (Hamilton and Beck depression and anxiety inventories). Compararam-se os resultados aos índices obtidos pela DYBOCS e a outras variáveis clínicas relacionadas ao TOC. RESULTADOS: Encontraram-se correlações estatísticas entre gravidade das dimensões agressividade e contaminação, com maior acomodação familiar. Foi verificado também maior criticismo por parte dos pacientes portadores de colecionismo. CONCLUSÃO: Diferentes subtipos de TOC exercem diferentes padrões de influência no contexto familiar. Mais estudos com esse enfoque são necessários para melhor orientação comportamental a pacientes e familiares.

MemoBoard familiar

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Joint modelling of longitudinal and survival data on breast cancer

Tese de Doutoramento em Ciências (Especialidade em Matemática)

Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria

Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.