Browsing by Author "Serrano, I"
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- Alterações Estruturais dos Vasos Pulmonares e Artérias Coronárias na Síndrome do Coração Esquerdo HipoplásicoPublication . Macedo, A; Pinto, E; Ramos, S; Brito, MJ; Costa, MM; Serrano, I; Torrezão, I; Lima, M; Silva, E; Roriz, ML; Silva, S; Sampayo, FCom o objectivo de correlacionar variantes anatómicas com alterações pulmonares e coronárias na síndrome do coração esquerdo hipoplásico (SCEH), fez-se o estudo morfológico e histológico de 15 peças de necrópsia coração-pulmão de recém-nascidos falecidos com aquela patologia. Encontrou-se a forma clássica de SCEH em II peças das quais 3 tinham atrésia da válvula mitral. Nas restantes 4 a aorta saía do ventrículo direito, com ventrículo esquerdo virtual e atrésia da válvula mitral. A histologia pulmonar mostrou aumento da percentagem de espessura das arteríolas e veias pulmonares e extensão intra-acinar da camada muscular das arteríolas em todas as peças. Mas em 8 peças com foramen ovale encerrado ou com diâmetro médio de 5 mm as alterações pulmonares foram mais marcadas do que nas restantes com diâmetro médio do foramen ovale de 9mm. A distribuição coronária foi normal, mas 4 das 8 peças com válvula mitral permeável apresentavam alterações das artérias coronárias não encontradas nas 7 peças com atrésia da válvula mitral. Conclui-se que na SCEH, a existência de foramen ovale encerrado ou restritivo, e de válvula mitral permeável, podem condicionar alterações pulmonares e coronárias, aumentando o risco cirúrgico pelas complicações pós operatórias que possam induzir.
- Inhibition of Fucosylation in Human Invasive Ductal Carcinoma Reduces E-Selectin Ligand Expression, Cell Proliferation, and ERK1/2 and p38 MAPK ActivationPublication . Carrascal, M; Silva, M; Ramalho, J; Pen, C; Martins, M; Pascoal, C; Amaral, C; Serrano, I; Oliveira, MJ; Sackstein, R; Videira, PBreast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLeX/A antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLeX/A expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.