Browsing by Author "Botelho, Mónica C."
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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.
- Commentary: Theileria Parasites Secrete a Prolyl Isomerase to Maintain Host Leukocyte TransformationPublication . Fernandes, Ruben; Ferreira, Stephanie; Botelho, Mónica C.The genus Theileria comprises apicomplexan parasites that are tick-transmitted and infect ruminants with important trade and industry impact in endemic countries. Infectious agents build up elaborate machinery to work together by means of host cell pathways and takeover their genetic and epigenetic mechanisms to modify phenotypic status of host cells. Among the Apicomplexa phylum encompassing obligate intracellular parasites, the only genus that introduces its DNA into mammalian host cells is Theileria, which is known to cause veterinary and human diseases. Various species, including Theileria parva and Theileria annulata, infect leukocytes causing alterations in their phenotypes that are common with several cancers, remarkably immortalization, hyperproliferation, and spreading. (...)
- 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.
- O papel dos estrogénios e vias de sinalização do recetor de estrogénio no cancro e infertilidade associados a schistosomosePublication . Botelho, Mónica C.O Schistosoma haematobium é um verme parasita que infecta mais de 100 milhões de indivíduos, principalmente no mundo em desenvolvimento. É o agente causador da schistosomose urogenital e tem sido associado com alta incidência de carcinoma de células escamosas da bexiga (SCC). A schistosomose haematobia também parece influenciar negativamente a fertilidade, particularmente a infertilidade feminina. Dado que os estrogénios e receptores de estrogénio são elementos chave na reprodução humana, e que os schistosomas produzem moléculas similares ao estrogénio, é provavel que este parasita seja causa de infertilidade através de desequilíbrios hormonais. No presente trabalho discutimos novos dados sobre o papel dos estrogénios e receptores de estrogénio tanto na carcinogénese como na infertilidade associadas a schistosomose urogenital.
- Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: an oestrogen-DNA adducts mediated pathway?Publication . Botelho, Mónica C.; Vale, N.; Gouveia, M.J.; Rinaldi, G.; Santos, J.; Santos, L.L.; Gomes, P.; Brindley, P.J.; Correia da Costa, José ManuelChronic infection with the blood fluke, Schistosoma haematobium, is associated with squamous cell carcinoma of the bladder. Previously, it has been shown that soluble extracts of mixed sex adult S. haematobium worms (SWAP) are tumourigenic, both in vitro and in vivo. In addition, oestrogen-related molecules in SWAP of S. haematobium down-regulate oestrogen receptors (ERs) alpha and beta in oestrogen responsive cells. Moreover, schistosome oestrogens occur in sera of persons with schistosomiasis haematobia and repress transcription of ERs in urothelial cells. Given that eggs of S. haematobium are the developmental stage directly responsible for urogenital disease during schistosomiasis haematobia, we suspected that soluble antigens from S. haematobium eggs exhibit similar or more potent tumorigenic capacity. Here we investigated the tumorigenic potential of soluble egg antigens (Sh-SEA) of S. haematobium and the endocrine system in favouring parasitism by schistosomes. The findings confirmed that 6.25μg/ml of Sh-SEA was enough to stimulate cell proliferation, reduce apoptosis and increase oxidative stress of Sh-SEA-exposed urothelial cells. In addition, genotoxic effects of Sh-SEA on these cells were determined by using alkaline single-cell gel electrophoresis (Comet). Furthermore, Liquid Chromatography Diode Array Detection Electron Spray Ionisation Mass Spectrometry indicated the presence of catechol-oestrogens in S. haematobium SEA. A prospective oestrogen-DNA adduct mediated pathway in S. haematobium egg induced bladder cancer is also discussed.