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Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy agai...

Silva, G; Sales-Dias, J; Casal, D; Alves, S; Domenici, G; Barreto, C; Matos, C; Lemos, A; Matias, A; Kucheryava, K; Ferreira, A; Moita, MR; Braga, S

The Notch-signaling ligand DLL1 has emerged as an important player and promising therapeutic target in breast cancer (BC). DLL1-induced Notch activation promotes tumor cell proliferation, survival, migration, angiogenesis and BC stem cell maintenance. In BC, DLL1 overexpression is associated with poor prognosis, particularly in estrogen receptor-positive (ER+) subtypes. Directed therapy in early and advanced BC...


BD-2 and BD-3 Increase Skin Flap Survival in a Model of Ischemia and Pseudomona...

Casal, D; Iria, I; Ramalho, JS; Alves, S; Mota-Silva, E; Mascarenhas-Lemos, L; Pontinha, C; Guadalupe-Cabral, M; Ferreira-Silva, J; Ferraz-Oliveira, M

The main aim of this work was to study the usefulness of human β-defensins 2 (BD-2) and 3 (BD-3), which are part of the innate immune system, in the treatment of infected ischemic skin flaps. We investigated the effect of transducing rat ischemic skin flaps with lentiviral vectors encoding human BD-2, BD-3, or both BD-2 and BD-3, to increase flap survival in the context of a P. aeruginosa infection associated w...


Staining of E-Selectin Ligands on Paraffin-Embedded Sections of Tumor Tissue

Carrascal, M; Talina, C; Borralho, P; Gonçalo Mineiro, A; Henriques, AR; Pen, C; Martins, M; Braga, S; Sackstein, R; Videira, P

BACKGROUND: The E-selectin ligands expressed by cancer cells mediate adhesion of circulating cancer cells to endothelial cells, as well as within tissue microenvironments important for tumor progression and metastasis. The identification of E-selectin ligands within cancer tissue could yield new biomarkers for patient stratification and aid in identifying novel therapeutic targets. The determinants of selectin ...


Inhibition of Fucosylation in Human Invasive Ductal Carcinoma Reduces E-Selecti...

Carrascal, M; Silva, M; Ramalho, J; Pen, C; Martins, M; Pascoal, C; Amaral, C; Serrano, I; Oliveira, MJ; Sackstein, R; Videira, P

Breast 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 t...


Reconstruction of a Long Defect of the Ulnar Artery and Nerve with an Arteriali...

Casal, D; Pais, D; Mota-Silva, E; Pelliccia, G; Iria, I; Videira, P; Mendes, MM; Goyri-O'Neill, J; Mouzinho, MM

There is evidence that nerve flaps are superior to nerve grafts for bridging long nerve defects. Moreover, arterialized neurovenous flaps (ANVFs) have multiple potential advantages over traditional nerve flaps in this context. This paper describes a case of reconstruction of a long defect of the ulnar artery and nerve with an arterialized neurovenous free flap and presents a literature review on this subject. A...


E-selectin ligands in the human mononuclear phagocyte system: Implications for ...

Silva, M; Videira, P; Sackstein, R

The mononuclear phagocyte system comprises a network of circulating monocytes and dendritic cells (DCs), and "histiocytes" (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body's first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate...


Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cel...

Severino, P; Silva, M; Carrascal, M; Malagolini, N; Chiricolo, M; Venturi, G; Barbaro Forleo, R; Astolfi, A; Catera, M; Videira, P; Dall'Olio, F

Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galß1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaa2,3Galß1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase...


Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selecti...

Carrascal, M; Silva, M; Ramalho, J; Pen, C; Martins, M; Pascoal, C; Amaral, C; Serrano, I; Oliveira, MJ; Sackstein, R; Videira, P

Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A), and a-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 th...


Novel monoclonal antibody L2A5 specifically targeting sialyl-Tn and short glyca...

Loureiro, L; Sousa, D; Ferreira, D; Chai, W; Lima, L; Pereira, C; Lopes, C; Correia, V; Silva, L; Li, C; Santos, L; Ferreira, JA; Barbas, A; Palma, A

Incomplete O-glycosylation is a feature associated with malignancy resulting in the expression of truncated glycans such as the sialyl-Tn (STn) antigen. Despite all the progress in the development of potential anti-cancer antibodies, their application is frequently hindered by low specificities and cross-reactivity. In this study, a novel anti-STn monoclonal antibody named L2A5 was developed by hybridoma techno...


A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Casal, D; Pais, D; Iria, I; Mota-Silva, E; Almeida, MA; Alves, S; Pen, C; Farinho, A; Mascarenhas-Lemos, L; Ferreira-Silva, J; Ferraz-Oliveira, M

Free tissue transfer has been increasingly used in clinical practice since the 1970s, allowing reconstruction of complex and otherwise untreatable defects resulting from tumor extirpation, trauma, infections, malformations or burns. Free flaps are particularly useful for reconstructing highly complex anatomical regions, like those of the head and neck, the hand, the foot and the perineum. Moreover, basic and tr...


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