Targeting the serrated pathway of colorectal cancer with mutation in BRAF

A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.

CAREGIVING FOR A FAMILY MEMBER WITH HEAD AND NECK CANCER

Objective: To know the perception of informal caregivers regarding the care for a family member with head and neck cancer. Methods: Qualitative study conducted between March and May 2014 in the radiotherapy outpatient center of the Centro de Alta Complexidade em Oncologia – CACON (Oncology High Complexity Center) of the Hospital Universitário de Brasília – HUB (University Hospital of Brasília) using semi-structured interviews with nine caregivers about the experience of caring for family members. Data underwent Content Analysis and four units of meaning were identified: “Representation of cancer in the Family”, “The care as debt, individual reward or reconstruction of family ties”, “Repercussions of cancer on the caregiver’s personal life” and “Social support and network used by caregivers”. Results: Feelings of sadness and surprise at the moment of diagnosis were attributed to cancer, as well as the idea of punishment. The care was seen as personal satisfaction, accomplishment and opportunity for family rapprochement. Work overload and change in routine were altered functions. Religiosity, exchange of experience in the waiting room and institutional support appeared as coping strategies. Conclusion: The experience of caring for family members with head and neck cancer directly interferes in the lives of caregivers. Pointing out the institutional embracement as a strategy within the social network reinforces the importance of integrating the caregivers as a significant part of the health care plan developed by the health team.

The cytokinesis-block micronucleus (CBMN) assay in human populations exposed to styrene: a systematic review and meta-analysis

Styrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial settings, especially among reinforced-plastics industry workers. The effect of occupational exposure to styrene on cytogenetics biomarkers has been previously reviewed with positive association observed for chromosomal aberrations, and inconclusive data for the micronucleus assay. Some limitations were noted in those studies, including inadequate exposure assessment and poor epidemiological design. Furthermore, in earlier studies micronuclei frequency was measured with protocols not as reliable as cytokinesis-block micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis is to investigate genomic instability and DNA damage as measured by the CBMN assay in lymphocytes of subjects exposed to styrene. A total of 11 studies published between 2004 and 2012 were included in the meta-analysis encompassing 479 styrene-exposed workers and 510 controls. The quality of each study was estimated by a quality scoring system which ranked studies according to the consideration of major confounders, exposure characterization, and technical parameters. An overall increase of micronuclei frequencies was found in styrene-exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18–1.52), with significant increases achieved in six individual studies. The consistency of results in individual studies, the independence of this result from major confounding factors and from the quality of the study strengthens the reliability of risk estimates and supports the use of the CBMN assay in monitoring genetic risk in styrene workers.

The impact of indoor air quality and contaminants on respiratory health of older people living in long-term care residences in Porto

Background: persons who are 65 years or older often spend an important part of their lives indoors thus adverse indoor climate might influence their health status. Objective: to evaluate the influence of indoor air quality and contaminants on older people’s respiratory health. Design: cross-sectional study. Setting: 21 long-term care residences (LTC) in the city of Porto, Portugal. Subjects: older people living in LTC with ≥65 years old. Methods: the Portuguese version of BOLD questionnaire was administered by an interviewer to older residents able to participate (n = 143). Indoor air contaminants (IAC) were measured twice, during winter and summer in 135 areas. Mixed effects logistic regression models were used to study the association between the health questionnaire results and the monitored IAC, adjusted for age, smoking habits, gender and number of years living in the LTC. Results: cough (23%) and sputum (12%) were the major respiratory symptoms, and allergic rhinitis (18%) the main selfreported illness. Overall particulate matter up to 2.5 micrometres in size median concentration was above the reference levels both in winter and summer seasons. Peak values of particulate matter up to 10 micrometres in size (PM10), total volatile organic compounds, carbon dioxide, bacteria and fungi exceeded the reference levels. Older people exposed to PM10 above the reference levels demonstrated higher odds of allergic rhinitis (OR = 2.9, 95% CI: 1.1–7.2). Conclusion: high levels of PM10 were associated with 3-fold odds of allergic rhinitis. No association was found between indoor air chemical and biological contaminants and respiratory symptoms.

Influência da doença oncológica na vivência da sexualidade

Enquadramento: A doença oncológica, independentemente da localização ou estadio, assim como os aspectos fisiológicos, psicológicos e sociais a ela associados podem resultar em prejuízo significativo ao nível do funcionamento sexual e relacional do doente. Objetivo: Identificar a influência da doença oncológica na vivência da sexualidade do doente oncológico. Métodos: Estudo de natureza quantitativa, exploratória e descritivo-correlacional, foi realizado com 330 utentes de um Centro Hospitalar na região centro, constituída por 61,5% mulheres e 38,5% homens, com idades compreendidas entre os 25 e os 84 anos (M= 56,05; DP= 12,16). Instrumento de colheita de dados composto por questionário de caracterização sociodemográfica, clínica e a Escala de Apgar Familiar, Smilkstein (1978); Escala de Imagem Corporal (Hopwood, et al 2001); Escala Reduzida de Ajustamento Mental ao Cancro (Watson et al, 1988); Questionário de Satisfação com o Relacionamento Sexual (Cappelleri et al, 2002). Resultados: Da amostra 81,1% é casada ou vive em união de facto, em relação à localização do cancro, 37,9% é localizado na mama e 31,8% digestivo. Relacionamento conjugal antes da doença muito satisfatório (45, 15% ) vs 32,12% nada/pouco satisfatório atualmente. Verificam-se diferenças estatísticamente significativas em algumas variáveis sóciodemográficas (idade, escolaridade), clínicas (localização do tumor, tratamento efetuado), funcionalidade familiar, imagem corporal e ajustamento mental ao cancro, na vivênvia da sexualidade pelo doente oncológico. Conclusão: A assistência aos portadores de doença oncológica deve incluir intervenções dirigidas ao despiste e tratamento da disfunção da sexualidade assim como ao planeamento de ações educativas/formativas dos profissionais de saúde no âmbito da sexualidade do doente oncológico. Palavras-chave: Doença Oncológica; Sexualidade; Imagem corporal; Ajustamento mental.

Estudo da composição e das propriedades bioactivas de plantas produtoras de bagas

O consumo de frutas e vegetais tem sido associado à prevenção de várias doenças crónicas, nomeadamente doenças cardiovasculares, diabetes, cancro e outras que envolvam processos inflamatórios. As bagas destacam-se pelo seu elevado conteúdo em polifenóis, cujas propriedades antioxidantes contribuem para a manutenção da saúde humana. O presente trabalho teve como alvo de estudo as diferentes partes morfológicas (bagas e folhas) de espécies produtoras de bagas, nomeadamente Elaeagnus umbellata, a Rubus grandofolius, a Sambucus lancolata, a Vaccinium padifolium e a Vaccinium cylindraceum, tendo em vista a sua valorização como produtos alimentares e/ou nutracêuticos. A caracterização físico-química destas espécies permitiu determinar que o teor total de sólidos solúveis (TSS) das bagas varia de 4,4 a 16,5 °Brix. As bagas demonstraram ser a parte morfológica com teor de humidade mais elevado. A análise do perfil fenólico por HPLC-DAD-ESI/MSn, no modo negativo, dos extractos metanólicos mostrou que as folhas apresentam maior conteúdo de compostos fenólicos, comparativamente às bagas. Os ácidos hidroxicinâmicos (derivados dos ácidos cafeicos, cumárico e ferúlico), os ácidos cafeoilquínicos, bem como os flavonóis-O-glicosilados (derivados da quercetina e canferol) predominam nestas espécies. A análise pelo modo positivo permitiu a identificação de antocianinas glicosiladas (delfinidina, cianidina, petunidina, peonidina e malvidina) nas bagas e folhas jovens da espécie Vaccinium padifolium. Os ensaios in vitro de simulação da digestão gastrointestinal permitiram compreender a sua influência na actividade antioxidante dos extractos. Após a digestão, as folhas continuam a apresentar maior capacidade antioxidante do que as bagas. Adicionalmente, concluiu-se que as enzimas presentes neste processo têm menor influência do que o pH e a força iónica dos sucos digestivos. O estudo do efeito inibitório in vitro dos extractos sobre a actividade de enzimas responsáveis pelo metabolismo dos hidratos de carbono permitiu determinar que os viii Joana Pinto (2016) extractos foram mais eficientes na inibição da actividade da α-glucosidase do que na inibição da actividade da α-amilase.

The third dimension: new developments in cell culture models for colorectal research

Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffoldfree or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology.

Association between common lipid metabolism genes polymorphisms and sporadic colorectal adenocarcinoma risk

Lipids can modulate the risk of developing sporadic colorectal adenocarcinoma (SCA), since alterations into lipid metabolism and transport pathways influence directly cholesterol and lipids absorption by colonic cells and indirectly reactive oxygen species (ROS) synthesis in rectum cells due to lipid accumulation. Lipid metabolism is regulated by several proteins APOA1, APOB, APOC3, APOE, CETP, NPY, PON1 and PPARG that could influence both metabolism and transport processes. Is been reported that several common single-nucleotide polymorphisms (SNPs) in these genes could influence their function and/or expression, changing lipid metabolism balance. Thus, genetic changes in those genes can influence SCA development, once the majority of them were never studied in this disease. Furthermore, there are contradictory results between some studied polymorphisms and SCA risk. Thus, the aim of this study was to explore and describe lipid metabolism-associated genes common polymorphisms (APOA1 -75 G>A; APOB R3500Q; APOC3 C3175G, APOC3 T3206G; APOE Cys112/158Arg; CETP G279A, CETP R451Q; NPY Leu7Pro; PON1 Q192R; PPARG Pro12Ala) status among SCA, and their relationship with SCA risk. Genotyping of common lipid metabolism genes polymorphisms (APOA1 75 G>A; APOB R3500Q; APOC3 C3175G, APOC3 T3206G; APOE Cys112/158Arg; CETP G279A, CETP R451Q; NPY Leu7Pro; PON1 Q192R; PPARG Pro12Ala) were done by PCR-SSP techniques, from formalin-fixed and paraffin-embedded biopsies of 100 healthy individuals and 68 SCA subjects. Mutant genotypes of APOA1 -75AA (32% vs 12%; p=0.001; OR=3.51; 95% CI 1.59-7.72); APOB 3500AA (7% vs 0%; p=0.01); APOC3 3175GG (19% vs 2%; p=0.0002; OR=11.58; 95% CI 2.52-53.22), APOC3 3206GG (19% vs 0%; p<0.0001); CETP 279AA (12% vs 1%; p=0.003; OR=13.20; 95% CI 1.61-108.17), CETP 451AA (16% vs 0%; p<0.0001); NPY 7CC (15% vs 0%; p<0.0001); PPARG 12GG (10% vs 0%; p=0.001); and heterozygote genotype PON1 192AG (56% vs 22%; p<0.0001; OR=4.49; 95% CI 2.298.80) were found associated with SCA prevalence. While, APOE E4/E4 (0% vs 8%; p=0.02) mutant haplotype seemed to have a protective effect on SCA. Moreover, it also been founded differences between APOB 3500GA, APOC3 3206TG, CETP 279AA genotypes and PPARG 12Ala allele prevalence and tissue localization (colon vs rectum). These findings suggest a positive association between most of common lipid metabolism genes polymorphisms studied and SCA prevalence. Dysregulation of APOA1, APOB, APOC3, CETP, NPY, PON1 and PPARG genes could be associated with lower cholesterol plasma levels and increase ROS among colon and rectum mucosa. Furthermore, these results also support the hypothesis that CRC is related with intestinal lipid absorption decrease and secondary bile acids production increase. Moreover, the polymorphisms studied may play an important role as biomarkers to SCA susceptibility.

Association between common lipid metabolism genes polymorphisms and sporadic colorectal adenocarcinoma risk

Lipids can modulate the risk of developing sporadic colorectal adenocarcinoma (SCA), since alterations into lipid metabolism and transport pathways influence directly cholesterol and lipids absorption by colonic cells and indirectly reactive oxygen species (ROS) synthesis in rectum cells due to lipid accumulation. Lipid metabolism is regulated by several proteins APOA1, APOB, APOC3, APOE, CETP, NPY, PON1 and PPARG that could influence both metabolism and transport processes. Is been reported that several common single-nucleotide polymorphisms (SNPs) in these genes could influence their function and/or expression, changing lipid metabolism balance. Thus, genetic changes in those genes can influence SCA development, once the majority of them were never studied in this disease. Furthermore, there are contradictory results between some studied polymorphisms and SCA risk. Thus, the aim of this study was to explore and describe lipid metabolism-associated genes common polymorphisms (APOA1 -75 G>A; APOB R3500Q; APOC3 C3175G, APOC3 T3206G; APOE Cys112/158Arg; CETP G279A, CETP R451Q; NPY Leu7Pro; PON1 Q192R; PPARG Pro12Ala) status among SCA, and their relationship with SCA risk. Genotyping of common lipid metabolism genes polymorphisms (APOA1 75 G>A; APOB R3500Q; APOC3 C3175G, APOC3 T3206G; APOE Cys112/158Arg; CETP G279A, CETP R451Q; NPY Leu7Pro; PON1 Q192R; PPARG Pro12Ala) were done by PCR-SSP techniques, from formalin-fixed and paraffin-embedded biopsies of 100 healthy individuals and 68 SCA subjects. Mutant genotypes of APOA1 -75AA (32% vs 12%; p=0.001; OR=3.51; 95% CI 1.59-7.72); APOB 3500AA (7% vs 0%; p=0.01); APOC3 3175GG (19% vs 2%; p=0.0002; OR=11.58; 95% CI 2.52-53.22), APOC3 3206GG (19% vs 0%; p<0.0001); CETP 279AA (12% vs 1%; p=0.003; OR=13.20; 95% CI 1.61-108.17), CETP 451AA (16% vs 0%; p<0.0001); NPY 7CC (15% vs 0%; p<0.0001); PPARG 12GG (10% vs 0%; p=0.001); and heterozygote genotype PON1 192AG (56% vs 22%; p<0.0001; OR=4.49; 95% CI 2.298.80) were found associated with SCA prevalence. While, APOE E4/E4 (0% vs 8%; p=0.02) mutant haplotype seemed to have a protective effect on SCA. Moreover, it also been founded differences between APOB 3500GA, APOC3 3206TG, CETP 279AA genotypes and PPARG 12Ala allele prevalence and tissue localization (colon vs rectum). These findings suggest a positive association between most of common lipid metabolism genes polymorphisms studied and SCA prevalence. Dysregulation of APOA1, APOB, APOC3, CETP, NPY, PON1 and PPARG genes could be associated with lower cholesterol plasma levels and increase ROS among colon and rectum mucosa. Furthermore, these results also support the hypothesis that CRC is related with intestinal lipid absorption decrease and secondary bile acids production increase. Moreover, the polymorphisms studied may play an important role as biomarkers to SCA susceptibility.

Mastectomia e corporalidade: impacto da cirurgia estético-reconstrutiva

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Clínica,

A tecnologia no ensino da interpretação

Tese de Mestrado em Tradução e Interpretação Especializadas Área Científica de Línguas e Culturas

Estudo da proteína humana centrossomal TBCCD1 em condições de stress oxidativo causado por H2O2 em estado estacionário

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Estratificação pré-terapêutica do carcinoma do endométrio por ressonância magnética - papel do estudo dinâmico após administração de contraste endovenoso e do estudo ponderado em difusão

O carcinoma do endométrio apresenta uma taxa de incidência em Portugal de cerca de 7.2%, sendo a 5ª neoplasia mais comum na mulher. Apesar de apresentar uma prevalência relativamente elevada, o seu prognóstico global é favorável, uma vez que 75% dos casos são diagnosticados em estádio precoce. O estudo por ressonância magnética é geralmente efectuado após a realização de uma ecografia para avaliação de uma hemorragia uterina anormal e após o diagnóstico histológico por histeroscopia ou ressecção. Contudo, a ressonância magnética pode apresentar um papel determinante no diagnóstico em casos de impossibilidade de biópsia e nos quais a biópsia é inconclusiva. Além do mais, apesar de esta técnica não ser contemplada na classificação para o estadiamento do carcinoma do endométrio da International Federation of Gynecology and Obstetrics de 2009, apresenta uma função fundamental no estadiamento pré-operatório destas doentes, sendo crucial para definir a abordagem cirúrgica e terapêutica. No presente artigo, as autoras descrevem o estado da arte da ressonância magnética funcional no diagnóstico e no estadiamento do carcinoma do endométrio, chamando a atenção para o papel do estudo dinâmico após administração de contraste endovenoso e do estudo ponderado em difusão nestes cenários através da revisão da literatura mais recente sobre este tópico.

Efeitos ginecológicos do "tamoxifeno": contributo da radiologia

O “Tamoxifeno” (TAM) é a terapêutica anti-estrogénica de escolha nas doentes com cancro da mama. Os efeitos proliferativos do TAM em idade pós-menopausa têm sido associados a hiperplasia, pólipos, carcinoma e sarcoma do endométrio. As doentes tratadas com TAM têm também maior incidência de leiomiomas, adenomiose e endometriose, assim como maior risco de quistos do ovário. O método de primeira linha na vigilância das mulheres sob TAM é a ecografia transvaginal (US-TV). O endométrio apresenta-se frequentemente espessado e com áreas quísticas, aspectos passíveis de melhor caracterização por histerossonografia e ressonância magnética. Nas imagens ponderadas em T2, um endométrio espessado e heterogéneo com captação de aspecto reticulado e a opacificação da interface endométrio-miométrio associam-se a lesões de pior prognóstico (pólipos, hiperplasia atípica e neoplasia). O conhecimento dos efeitos ginecológicos do TAM e da sua tradução radiológica promove o diagnóstico precoce e adequado encaminhamento destas doentes.