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Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogram...

Afonso, Julieta Alexandra Pereira; Matos, Ana Catarina Barbosa; Silvestre, Ricardo Jorge Leal; Pereira-Vieira, Joana; Gonçalves, Samuel Martins

Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919)...


Prognostic value of Monocarboxylate Transporter 1 overexpression in cancer: a s...

Silva, Ana; Cerqueira, Mónica Costa; Rosa, Beatriz; Sobral, Catarina; Pinto-Ribeiro, Filipa; Costa, Marta Sílvia Freitas; Baltazar, Fátima

Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systema...


Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple...

Ferreira, Débora Carina Gonçalves Abreu; Pereira, Cátia Sofia Santos; Costa, Marta; Afonso, Julieta Alexandra Pereira; Yang, Sujuan; Hensel, Janine

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed tha...


Exploring the diversity of visceral, subcutaneous and perivascular adipose tiss...

Ferreira, Joana; Afonso, Julieta Alexandra Pereira; Carneiro, Alexandre Lima; Vila, Isabel; Cunha, Cristina; Roque, Susana; Silva, Cristina

The prevalence of obesity has doubled, with a concomitant increase in cardiovascular disease. This study aimed to compare the characteristics of visceral, subcutaneous and peri-aortic adipose tissue determined with computed tomography (CT) scans and to correlate them with cardiovascular risk factors, anthropometric measures and medication. An observational and prospective study was conducted, and 177 subjects w...


In vivo anticancer activity of AZD3965: a systematic review

Silva, Ana; Antunes, Beatriz; Batista, Alberta; Pinto-Ribeiro, Filipa; Baltazar, Fátima; Afonso, Julieta Alexandra Pereira

Proliferating cancer cells have high energy demands, which is mainly obtained through glycolysis. The transmembrane trafficking of lactate, a major metabolite produced by glycolytic cancer cells, relies on monocarboxylate transporters (MCTs). MCT1 optimally imports lactate, although it can work bidirectionally, and its activity has been linked to cancer aggressiveness and poor outcomes. AZD3965, a specific MCT1...


Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma ...

Afonso, Julieta Alexandra Pereira; Pinto, Tatiana; Sousa, Susana Patrícia Simões; Schmitt, Fernando; Longatto, Adhemar; Pinheiro, Céline

Increased glycolytic activity with accumulation of extracellular lactate is regarded as a hallmark of cancer. In lymphomas, FDG-PET has undeniable diagnostic and prognostic value, corroborating that these tumours are avid for glucose. However, the role of glycolytic metabolism-related molecules in lymphoma is not well known. Here, we aimed to evaluate the clinical and prognostic significance of a panel of glyco...


Metabolic coupling in urothelial bladder cancer compartments and its correlatio...

Afonso, Julieta Alexandra Pereira; Santos, Lúcio L.; Morais, A.; Amaro, Teresina; Longatto Filho, Adhemar; Baltazar, Maria de Fátima Monginho

Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladd...


Evolving hallmarks in urothelial bladder cancer: unveiling potential biomarkers

Afonso, Julieta Alexandra Pereira; Freitas, R.; Lobo, F.; Morais, A.; Amaro, T.; Reis, R. M.; Baltazar, Fátima; Longatto Filho, Adhemar; Santos, L.

Urothelial bladder carcinoma (UBC), the most frequent type (90%) of bladder cancer and the second most common malignancy of the urogenital region, is a relatively well understood type of cancer, with numerous studies concerning pathogenetic pathways, natural history and bladder tumor biology being reported. Despite this, it continues to remain a challenge in the oncology field, mostly due to its relapsing and p...


CD147 and MCT1 - potential partners in bladder cancer aggressiveness and cispla...

Afonso, Julieta Alexandra Pereira; Santos, Lúcio; Gonçalves, Vera M.; Morais, António; Amaro, T.; Longatto Filho, Adhemar; Baltazar, Fátima

The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpres...


Urothelial bladder cancer progression: lessons learned from the bench

Baltazar, Fátima; Afonso, Julieta Alexandra Pereira; Longatto Filho, Adhemar; Reis, R. M.

Urothelial bladder carcinoma (UBC) is an intricate malignancy with a variable natural history and clinical behavior. Despite developments in diagnosis/prognosis refinement and treatment modalities, the recurrence rate is high, and progression from non-muscle to muscle invasive UBC commonly leads to metastasis. Moreover, patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy ...


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