Percorrer por autor "Fonseca, Joana"
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- An overview of the spindle assembly checkpoint status in oral cancerPublication . Teixeira, Jose Henrique; Silva, Patrícia; Reis, Rita Margarida; Moura, Ines Moranguinho; Marques, Sandra; Fonseca, Joana; Monteiro, Luis Silva; Bousbaa, HassanAbnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20.
- Immunological resilience of a temperate catshark to a simulated marine heatwavePublication . Martins Rebocho, Sandra; Ferreira, Cristina; Mateus, Ana Patrícia; Santos, Catarina Pereira; Fonseca, Joana; Rosa, Rui; Power, Deborah MaryMarine heatwaves (MHWs) have recently been proposed to be more relevant in driving population changes than the continuous increase in average temperatures associated with climate change. The causal processes underpinning MHW effects in sharks are unclear but may be linked to changes in fitness caused by physiological trade-offs that influence the immune response. Considering the scarcity of data about the immune response of sharks under anomalous warming events, the present study analyzed several fitness indices and characterized the immune response (in the blood, epigonal organ, liver, spleen and intestine) of temperate adult small-spotted catsharks (Scyliorhinus canicula) after a 30 day exposure to a category II MHW. The results indicated that adult small-spotted catsharks have developed coping strategies for MHWs. Specifically, among the 35 parameters investigated, only the gonad-to-body ratio (GBR) and plasma glucose concentration showed significant increases. In contrast, gene expression of igm and tumor necrosis factor receptor (tnfr) in blood cells, and tnfr in the epigonal organ, as well as the number of monocytes, all significantly decreased. Although a decline in immune function in small-spotted catsharks was revealed following MHW exposure, energy mobilization restored homeostasis and indicated a shift in energy allocation towards reproduction. Group resilience may be due to the variable tolerance of individuals, the phenotypic plasticity of cellular immunity, thermal imprinting and/or metabolic capacity of the individuals.
- Prenylated chalcone 2 ccts as an antimitotic agent and enhances the chemosensitivity of tumor cells to paclitaxelPublication . Fonseca, Joana; Marques, Sandra; Silva, PMA; Patrícia M.A. Silva; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena M.; Bousbaa, HassanWe previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination.