Percorrer por autor "Oliveira, Paula A."
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- Carcinogenic Ability of Schistosoma Haematobium Possibly through Oncogenic Mutation of KRAS GenePublication . Botelho, Mónica C.; Veiga, Isabel; Oliveira, Paula A.; Lopes, Carlos; Teixeira, Manuel; Costa, José M Correia da; Machado, José C.Schistosoma haematobium is a parasitic flatworm that infects millions of people, mostly in the developing world, and is associated with high incidence of bladder cancer, although why is not clear. Previously, we have used CD-1 mice to show that Schistosoma haematobium total antigen (Sh) has a carcinogenic ability. Sh intravesically instillation induced the development of several urothelial lesions, namely nodular hyperplasia and dysplasia (LGIUN—Low Grade Intra-Urothelial Neoplasia) after 40 weeks of treatment. These results suggested that Sh induce urothelium malignization. Bladder carcinoma frequently harbours gene mutations that constitutively activate the receptor tyrosine kinase-Ras pathway for this reason we studied activating mutations in KRAS gene. Twenty percent of the bladders with dysplasia presented a KRAS mutation in codon 12 of exon 2. We concluded from these results that the parasite extract of S. haematobium has carcinogenic ability possibly through oncogenic mutation of KRAS gene.
- Cystic Fibrosis modulator drugs inhibit migration of colorectal cancer cellsPublication . Vicente, Luana; Barros, Patrícia; Gonçalves, Vânia; Oliveira, Paula A.; Jordan, Peter; Matos, PauloColorectal cancer (CRC) remains a leading cause of cancer-related mortality, driven by complex genetic, epigenetic, and microenvironmental factors. Recent findings implicate the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in CRC progression, as CFTR levels are notably reduced in sporadic CRCs, particularly in advanced and metastatic tumors, correlating with poorer patient outcomes. Additionally, cystic fibrosis (CF) patients, who carry CFTR mutations, have a 6-fold increased risk of early-onset CRC. Given recent advances in small-molecule modulators that restore CFTR function in CF patients, this study explored the potential of repositioning these modulators to address CFTR downregulation in sporadic CRC. Using a panel of CRC cell lines, we investigated whether CFTR modulators can increase CFTR functional expression in cells with various genetic backgrounds and whether such improvements could reduce their oncogenic properties. Our data show that treatment with the CFTR folding correctors VX-661 and VX-445 led to a significant, approximately three-fold increase in CFTR abundance in CRC cells expressing reduced but detectable levels of the channel. Additionally, these treatments significantly reduced the migratory and invasive behavior of Caco-2 and DLD-1 cells, particularly when combined with the CFTR potentiator VX-770. Our findings suggest that CFTR modulators may hinder the oncogenic properties of CRC cells. Further in vivo studies are necessary to fully assess their potential benefits for repositioning as a CRC treatment.
- Do (xeno)estrogens pose a risk to earthworms? Soy isoflavones and estradiol impact gonad structure and induce oxidative stress in Eisenia fetidaPublication . Azevedo, Tiago; Silva-Reis, Rita; Medeiros-Fonseca, Beatriz; Gonçalves, Mariana; Mendes, Gabriel; Roboredo, Marta; Rocha, Maria J.; Peixoto, Francisco; Pinto, Maria de Lurdes; Matos, Manuela; Sousa, João R.; Oliveira, Paula A.; Coimbra, Ana M.Understanding the impact of endocrine disruptor compounds (EDCs) across a wide range of species is crucial, given their ubiquitous presence. Although invertebrate species lack sex steroid hormone pathways, they exhibit sensitivity to EDCs, which could affect population dynamics. This study assessed reproductive endpoints and oxidative stress parameters in Eisenia fetida following exposure to estradiol and soy isoflavones, resembling the concentrations found in livestock manure. The experiment used artificial soil, as recommended by OECD guidelines (7:2:1 sand, kaolin and peat). Adult specimens were randomly divided into seven groups (n = 11/replicate): one control, three estradiol (156.1, 283.4 and 633.8 μg/kg of dry soil) and three soy isoflavones (113.0, 215.3 and 405.0 mg/kg of dry soil) concentrations. After eight weeks, samples were collected for cytological, histological and biochemical analysis. Offspring development was assessed after 12 additional weeks. Higher estradiol and isoflavone concentrations led to lower germ cell number and increased abnormalities, especially in the seminal vesicles and ovaries. Catalase and peroxidase activities were significantly increased in all treated groups. The exposure did not significantly affect the number of E. fetida offspring. These findings highlight E. fetida’s sensitivity to EDCs at a biochemical and tissue level, suggesting its use as a bioindicator for assessing EDC contamination in soils.
- Granulomatous-like immune reaction and hepatic fibrosis induced by Schistosoma haematobium immature wormsPublication . Botelho, Mónica C.; Oliveira, Paula A.; Vieira, Paulo; Delgado, Maria de Lurdes; Lourenço, Ligia; Lopes, Carlos; Machado, José C .; Costa, José M Correia daGolden hamsters were inoculated with Schistosoma haematobium cercariae to examine histological lesions at different time points over an 18 month period of infection. Hamsters were sacrificed 26 weeks and 82 weeks after inoculation. The parasite was found in the blood and in the liver of infected animals as was expected, but we found exclusively male worms, no female worms nor eggs. Interestingly we observed unexpected hepatic lesions induced by S. haematobium immature male worms alone in the golden hamster, characteristic of schistosome eggs. Samples from liver, kidneys, lungs, bladder and gastrointestinal tract were collected during necropsy to evaluate injuries induced by S. haematobium. Notably we observed hepatitis in the liver of infected hamsters, no lesions were found in other organs. We also found liver fibrosis in infected hamsters. This study provides further experimental evidence for the role that schistosome worms, and their derived antigens, may play in the pathology of the infection and modulation of liver chronic inflammation in the murine model of schistosomiasis.