Evaluation of tissue and circulating mir-21 as potential biomarker of response to chemoradiotherapy in rectal cancer

This research received funding from European Structural & Investment Funds through the COMPETE Programme—Programa Operacional Regional de Lisboa—Programme Grant LISBOA-01-0145-FEDER-016405,and from National Funds through FCT—Fundação para a Ciência e a Tecnologia—Programme Grant SAICTPAC/0019/2015.Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre-and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40–6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45–7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.publishersversionpublishe

With mouse age comes wisdom : a review and suggestions of relevant mouse models for age-related conditions

Ageing is a complex multifactorial process that results in many changes in physiological changes processes that ultimately increase susceptibility to a wide range of diseases. As such an ageing population is resulting in a pressing need for more and improved treatments across an assortment of diseases. Such treatments can come from a better understanding of the pathogenic pathways which, in turn, can be derived from models of disease. Therefore the more closely the model resembles the disease situation the more likely relevant the data will be that is generated from them. Here we review the state of knowledge of mouse models of a range of diseases and aspects of an ageing physiology that are all germane to ageing. We also give recommendations on the most common mouse models on their relevance to the clinical situations occurring in aged patients and look forward as to how research in ageing models can be carried out. As we continue to elucidate the pathophysiology of disease, often through mouse models, we also learn what is needed to refine these models. Such factors can include better models, reflecting the ageing patient population, or a better phenotypic understanding of existing models

Evaluation of Tissue and Circulating miR-21 as Potential Biomarker of Response to Chemoradiotherapy in Rectal Cancer

Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre- and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40–6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45–7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.info:eu-repo/semantics/publishedVersio

Transporte aéreo: comunicação em redes móveis

Orientação: Mariana Cristina Melo Inácio Marques ; co-orientação: Paula Bela Rosa Luís LopesNas companhias aéreas, a internet também permitiu a origem de novos canais de distribuição favorecendo o contacto direto com os seus seguidores. Os dispositivos móveis, entre os quais os telefones inteligentes, são as plataformas ideais para promover, comunicar, distribuir e vender. A possibilidade de se comunicar sem qualquer tipo de intermediação permite o contacto direto com o consumidor final, de uma forma rápida e eficaz. Como comunicam as companhias aéreas quando utilizam dispositivos com acesso à internet? Dois objetivos específicos estão enunciados nesta dissertação de mestrado: 1) Elencar quais os serviços mais utilizados e, por outro lado, de que forma podem servir como estratégia de marketing e comunicação. 2) Diagnosticar que tipo de serviços são procurados pelo consumidor quando este utiliza um smartphone, tendo como foco a eficácia, a notoriedade da marca e a fidelização dos clientes. Na elaboração do inquérito foram pré-definidos serviços que os clientes poderiam utilizar quando navegassem numa aplicação móvel. Verificou-se através dos resultados que é possível catalogar diferentes comportamentos patentes nas preferências dos mesmos aquando da escolha dos serviços disponibilizados. Desta forma, é possível criar segmentos de mercado específicos, permitindo satisfazer necessidades e conhecer melhor os clientes.In airlines, the internet has also allowed new distribution channels, favoring direct contact with their followers. Mobile devices, including smartphones, are the ideal platforms for promoting, communicating, distributing and selling. The ability to communicate without any intermediation allows direct contact with the final consumer, quickly and effectively. How do airlines communicate when they use devices with internet access? Two specific objectives are set out in this master’s dissertation: 1) Which services are most used and, on the other hand, how can they serve as a marketing and communication strategy? 2) Diagnose what kind of services are sought by consumers when they use a smartphone, focusing on effectiveness, brand awareness and customer loyalty. In the survey, services were predefined which customers could use when browsing a mobile application. It was verified through the results that it is possible to catalogue different patent behaviors in the preferences when choosing the services. In this way it is possible to create more specific market segments, allowing to satisfy needs and to know the customers better

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

Funding: This work has received funding from European Structural and Investment Funds through the COMPETE Programme Grant LISBOA-01-0145-FEDER-016405, from National Funds through Fundação para a Ciência e Tecnologia Programme grant SAICTPAC/0019/2015 and by a cholar from the Portuguese Society of Coloproctology as Investigation in Coloproctology Research Prize 2016–2018.Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).publishersversionpublishe

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).info:eu-repo/semantics/publishedVersio

Cistoadenoma de glándulas salivales menores. Presentación de dos casos y revisión de la literatura

El cistoadenoma es un tumor salival benigno de origen epitelial muy infrecuente que se caracteriza por presentar múltiples proyecciones papilares y espacios microquísticos recubiertos de células cilíndricas o cuboideas. La OMS define el cistoadenoma como una neoplasia salival muy similar al tumor de Warthin, que carece de componente linfoide. La mayoría de cistoadenomas se han descrito a nivel de la laringe, la nasofaringe, así como en la glándula parótida y las glándulas lacrimales. Sin embargo, pueden localizarse con menor frecuencia en las mucosas labial y bucal, en la fosa tonsilar y en el paladar. El 35% se sitúan en las glándulas salivales menores

Nanoformulations of a potent copper-based aquaporin inhibitor with cytotoxic effect against cancer cells

Aim: Development of liposomal formulations of Cuphen, a potent copper-based aquaporin inhibitor with therapeutic potential against melanoma and colon cancer. Materials &amp; methods: Cuphen was incorporated into liposomes using the dehydration–rehydration method. The ability of Cuphen to induce cancer cell death was evaluated by MTS and ViaCount assays. In vivo toxicity studies were performed in BALB/c mice. Results: In vitro studies illustrated the antiproliferative effects of Cuphen in different cancer cell lines, in free form or after incorporation into liposomes. In vivo studies revealed no toxic effects after parenteral administration of Cuphen liposomes. Conclusions: Cuphen liposomes are highly attractive to be further tested in murine models due to the possibility of stabilizing and specifically deliver this metallodrug to tumor sites. </jats:p