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- Decrease of CD68 synovial macrophages in celastrol treated arthritic ratsPublication . Cascao, Rita; Vidal, Bruno; Lopes, Inês; Paisana, Eunice; Rino, José; Moita, Luis; Fonseca, João EuricoBackground: Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA). Methods: Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively. Results: Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects. Conclusions: Our results validate celastrol as a promising compound for the treatment of arthritis.
- Role of UBE2C in brain cancer invasion and disseminationPublication . Domentean, Stefani; Paisana, Eunice; Cascao, Rita; Faria, ClaudiaGlioblastoma (GB) and brain metastases (BM) are the most common brain tumors in adults and are invariably associated with a dismal outcome. These highly malignant tumors share common features including increased invasion and migration of the primary or metastatic brain cancer cells, whose triggering mechanisms are largely unknown. Emerging evidence has suggested that the ubiquitin-conjugating enzyme E2C (UBE2C), essential for controlling cell cycle progression, is overexpressed in diverse malignancies, including brain cancer. This review highlights the crucial role of UBE2C in brain tumorigenesis and its association with higher proliferative phenotype and histopathological grade, with autophagy and apoptosis suppression, epithelial-to-mesenchymal transition (EMT), invasion, migration, and dissemination. High expression of UBE2C has been associated with patients' poor prognosis and drug resistance. UBE2C has also been proven as a promising therapeutic target, despite the lack of specific inhibitors. Thus, there is a need to further explore the role of UBE2C in malignant brain cancer and to develop effective targeted therapies for patients with this deadly disease.
- Immunotherapy in lung cancer brain metastasesPublication . Paisana, Eunice; Cascao, Rita; Alvoeiro, Magda; Félix, Francisco; Martins, Guilherme; Guerreiro, Carla; Roque, Rafael; Cruz, Rafael Moiteiro Da; Pacheco, Teresa; Amado, Ana Cristina; Ferro, Filipa; Lopes Machado, Andrea; Vilariça, Ana Sofia; Hasmucrai, Direndra; Alves, Paula; Faria, ClaudiaBrain metastases (BM) occur frequently in lung cancer, particularly in non-small cell lung cancer (NSCLC) patients and remain a significant cause of morbidity and mortality. Standard therapies have limited efficacy due to poor crossing of the blood-brain barrier and the distinct features between BM and the primary tumor. This review explores the immune landscape of brain metastatic disease, emerging immunotherapeutic strategies, and promising biomarkers in NSCLC patients.