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Glycoproteomics identifies HOMER3 as a potentially targetable biomarker trigger...

Peixoto, A; Ferreira, D; Azevedo, R; Freitas, R; Fernandes, E; Relvas-Santos, M; Gaiteiro, C; Soares, J; Cotton, S; Teixeira, B; Paulo, P; Lima, L

Background: Muscle invasive bladder cancer (MIBC) remains amongst the deadliest genitourinary malignancies due to treatment failure and extensive molecular heterogeneity, delaying effective targeted therapeutics. Hypoxia and nutrient deprivation, oversialylation and O-glycans shortening are salient features of aggressive tumours, creating cell surface glycoproteome fingerprints with theranostics potential. Meth...


Target score—a proteomics data selection tool applied to esophageal cancer iden...

Cotton, S; Ferreira, D; Soares, J; Peixoto, A; Relvas-Santos, M; Azevedo, R; Piairo, P; Diéguez, L; Palmeira, C; Lima, L; Silva, AMN; Santos, LL

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a g...


Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microf...

Carvalho, S; Abreu, CM; Ferreira, D; Lima, L; Ferreira, JA; Santos, LL; Ribeiro, R; Grenha, V; Martínez-Fernández, M; Duenas, M; Suárez-Cabrera, C

Bladder cancer is the most common malignancy of the urinary tract, having one of the highest recurrence rates and progression from non-muscle to muscle invasive bladder cancer that commonly leads to metastasis. Cystoscopy and urine cytology are the standard procedures for its detection but have limited clinical sensitivity and specificity. Herein, a microfluidic device, the UriChip, was developed for the enrich...


TERT promoter mutation as a potential predictive biomarker in BCG-treated bladd...

Batista, R; Lima, L; Vinagre, J; Pinto, V; Lyra, J; Máximo, V; Santos, L; Soares, P

Telomerase reverse transcriptase gene promoter (TERTp) mutations are recognized as one of the most frequent genetic events in bladder cancer (BC). No studies have focused on the relevance of TERTp mutations in the specific group of tumors treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Methods — 125 non muscle invasive BC treated with BCG therapy (BCG-NMIBC) were screened for TERTp mutations, ...


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...


CD44 glycoprotein in cancer: A molecular conundrum hampering clinical applications

Azevedo, R; Gaiteiro, C; Peixoto, A; Relvas-Santos, M; Lima, L; Santos, L; Ferreira, JA

CD44 is a heavily glycosylated membrane receptor playing a key role in cell adhesion, signal transduction and cytoskeleton remodelling. It is also one of the most studied glycoproteins in cancer, frequently explored for stem cell identification, and associated with chemoresistance and metastasis. However, CD44 is a general designation for a large family of splicing variants exhibiting different degrees of glyco...


Frequency of TERT promoter mutations in human cancers

Vinagre, J; Almeida, A; Pópulo, H; Batista, R; Lyra, J; Pinto, V; Coelho, R; Celestino, R; Prazeres, H; Lima, L; Melo, M; Rocha, AG; Preto, A; Castro, P

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring tog...


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