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Deciphering the influence of CD276 glycocode in gastric cancer immunoregulation

Magalhães, Mariana; Dourado-Gonçalves, Martina; Santos, Lúcio Lara; Peixoto, Andreia; Ferreira, José Alexandre

Gastric cancer (GC) ranks 5th globally in incidence and cancer-related mortality, with advanced-stage 5-year survival rates below 20%1,2, unveiling the need for novel immunotherapies. CD276, an immune checkpoint molecule, is related to immune evasion and tumour progression in GC3-5. In turn, aberrant glycosylation, especially truncated O-glycans, Tn and Sialyl-Tn, correlates with GC aggressiveness and poor prog...


Glycoengineered nanoparticles enhance the delivery of 5-fluoroucil and paclitax...

Fernandes, Elisabete; Ferreira, Dylan; Peixoto, Andreia; Freitas, Rui; Relvas-Santos, Marta; Palmeira, Carlos; Martins, Gabriela; Barros, Anabela

Gastric cancer is the third leading cause of cancer-related death worldwide, with half of patients developing metastasis within 5 years after curative treatment. Moreover, many patients cannot tolerate or complete systemic treatment due severe side-effects, reducing their effectiveness. Thus, targeted therapeutics are warranted to improve treatment outcomes and reduce toxicity. Herein, poly(lactic-co-glycolic a...


Glycan affinity magnetic nanoplatforms for urinary glycobiomarkers discovery in...

Azevedo, Rita; Soares, Janine; Gaiteiro, Cristiana; Peixoto, Andreia; Lima, Luís; Ferreira, Dylan; Relvas-Santos, Marta; Fernandes, Elisabete

Bladder Cancer (BC) presents one of the highest recurrence rates amongst solid tumours and constitutes the second deadliest disease of the genitourinary track. Non-invasive identification of patients facing disease recurrence and/or progression remains one of the most critical and challenging aspects in disease management. To contribute to this goal, we demonstrate the potential of glycan-affinity glycoproteomi...


The predominance of M2-polarized macrophages in the stroma of low-hypoxic bladd...

Lima, Luís; Oliveira, Daniela; Tavares, Ana; Amaro, Teresina; Cruz, Ricardo; Ferreira, José Alexandre; Santos, Lúcio

OBJECTIVE: Bacillus Calmette-Guérin (BCG) immunotherapy is the gold standard treatment for superficial bladder tumors with intermediate/high risk of recurrence or progression. However, approximately 30% of patients fail to respond to the treatment. Effective BCG therapy needs precise activation of the type 1 helper cells immune pathway. Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phe...


FASL polymorphism is associated with response to bacillus Calmette-Guérin immun...

Lima, Luís; Ferreira, José Alexandre; Tavares, Ana; Oliveira, Daniela; Morais, António; Videira, Paula; Medeiros, Rui; Santos, Lúcio

Objective Deregulation of FAS/FASL system may lead to immune escape and influence bacillus Calmette-Guérin (BCG) immunotherapy outcome, which is currently the gold standard adjuvant treatment for high-risk non–muscle invasive bladder tumors. Among other events, functional promoter polymorphisms of FAS and FASL genes may alter their transcriptional activity. Therefore, we aim to evaluate the role of FAS and FASL...


The role of functional polymorphisms in immune response genes as biomarkers of ...

Lima, Luís; Oliveira, Daniela; Ferreira, José Alexandre; Tavares, Ana; Cruz, Ricardo; Medeiros, Rui; Santos, Lúcio

OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivaria...


P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Canceriza...

Santos, Júlio; Fernandes, Elisabete; Ferreira, José Alexandre; Lima, Luís; Tavares, Ana; Peixoto, Andreia; Parreira, Beatriz

BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since the...


Overexpression of tumour-associated carbohydrate antigen sialyl-Tn in advanced ...

Ferreira, José Alexandre; Videira, Paula; Lima, Luís; Pereira, Sofia; Silva, Mariana; Carrascal, Milene; Severino, Paulo; Fernandes, Elisabete

Little is known on the expression of the tumour-associated carbohydrate antigen sialyl-Tn (STn), in bladder cancer. We report here that 75% of the high-grade bladder tumours, presenting elevated proliferation rates and high risk of recurrence/progression expressed STn. However, it was mainly found in non-proliferative areas of the tumour, namely in cells invading the basal and muscle layers. STn was also found ...


Response of high-risk of recurrence/progression bladder tumours expressing sial...

Lima, Luís; Severino, Paulo; Silva, Mariana; Miranda, Andreia; Tavares, Ana; Pereira, Sofia; Fernandes, Elisabete; Cruz, Ricardo; Amaro, Teresina

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that m...


Identification of cell-surface mannans in a virulent Helicobacter pylori strain

Ferreira, José Alexandre; Azevedo, N. F.; Vieira, M. J.; Figueiredo, C.; Goodfellow, Brian J.; Monteiro, Mário A.; Coimbra, Manuel A.

With the intent of contributing to a carbohydrate-based vaccine against the gastroduodenal pathogen, Helicobacter pylori, we report here the structure of cell-surface mannans obtained from a virulent strain. Unlike other wild-type strains, this strain was found to express in good quantities this polysaccharide in vitro. Structural analysis revealed a branched mannan formed by a backbone of α-(1→6)-linked mannop...


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