Percorrer por autor "Brito, M"
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- Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised MedicinePublication . Alpuim Costa, D; Nobre, JG; Batista, MV; Ribeiro, C; Calle, C; Cortes, A; Marhold, M; Negreiros, I; Borralho, P; Brito, M; Cortes, J; Braga, SA; Costa, LBreast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC.
- Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised MedicinePublication . Alpuim Costa, D; Nobre, JG; Batista, MV; Ribeiro, C; Calle, C; Cortes, A; Marhold, M; Negreiros, I; Borralho, P; Brito, M; Cortes, J; Braga, SA; Costa, L
- Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical OncologistsPublication . Alpuim Costa, D; Nobre, JG; Fernandes, JP; Batista, MV; Simas, A; Sales, C; Gouveia, H; Ribeiro, LA; Coelho, A; Brito, M; Inácio, M; Cruz, A; Mariano, M; Savva-Bordalo, J; Fernandes, R; Oliveira, A; Chaves, A; Fontes-Sousa, M; Sampaio-Alves, M; Martins-Branco, D; Afonso, NAbstract Introduction: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. Methods: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. Results: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. Conclusion: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.
- The impact on productivity costs of reducing unemployment in patients with advanced breast cancer: A model estimation based on a Portuguese nationwide observational studyPublication . Vasconcelos de Matos, L; Borges, M; Oliveira, AT; Bulhosa, C; Miguel, LS; Fidalgo de Freitas, T; Cunha, R; Mendes, AD; Arede, AJ; Marques, C; Costa, DA; Correia, JA; Brito, M; Fontes e Sousa, M; Guimarães, T; Cardoso, FThis study aimed to characterize the employment status and work-related conditions of patients with advanced breast cancer (ABC) in Portugal and quantify the productivity costs of premature abandonment of the work market while evaluating strategies to promote employment. The analysis was based on a cumulative incidence model for estimation of ABC prevalence and on a cross-sectional study characterizing the employment status of patients with ABC. This study was conducted in Portuguese hospitals, between Nov2021-Dec2022 and included patients diagnosed with ABC for at least 6 months, aged 66 or less and consenting for a self-answered questionnaire regarding work status. A total of 2151 working-aged women were estimated to have ABC in 2019 in Portugal, with productivity costs amounting to 28,676,754€ over 2019-2021. 112 patients from 9 hospitals were included in the study, average age was 52yr, 48 % had a postsecondary educational degree level and 87 % reported having a paid job at the time of diagnosis, mostly full-time. At the time of the study, only 38 % of the patients maintained the job status. The remaining were unemployed (51 %), on medical leave (25 %) or retired (24 %). Stop working was a personal choice for only 5 %. A subsidized part-time employment regimen, despite increased government costs, would allow a reduction in productivity costs, leading to a positive balance of 2,431,329€ over the same period. This study suggests that the majority of patients with ABC abandon the labor market before the age of retirement. Flexible work arrangements would benefit the patient, the government and the society.
- Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human healthPublication . Andaluz, S; Zhao, B; Sinha, S; Lagniton, PN; Alpuim Costa, D; Ding, X; Brito, M; Wang, SMBackground: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in Brazilian population, which has high degree Portuguese-heritage. Methods: By comprehensive data mining, standardization and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. Results: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese ( https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/ ) and an open database named dbBRCA-Brazilian ( https://genemutation.fhs.um.edu.mo/dbbrca-brazilian ) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations, and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. Conclusion: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.
- Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human healthPublication . Andaluz, S; Zhao, B; Sinha, S; Lagniton, PN; Alpium Costa, D; Ding, X; Brito, M; Wang, SMBackground: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in Brazilian population, which has high degree Portuguese-heritage. Methods: By comprehensive data mining, standardization and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. Results: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese ( https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/ ) and an open database named dbBRCA-Brazilian ( https://genemutation.fhs.um.edu.mo/dbbrca-brazilian ) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations, and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. Conclusion: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.