Percorrer por autor "Preto, Ana"
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- 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanismPublication . Vieira, Joana Pereira; Preto, Ana; Granja, Sara; Queirós, Odília; Celeiro, Sónia Pires; Ko, Young Hee; Casal, Margarida; Matos, Catarina Barbosa; Baltazar, Fátima; Granja, SaraAcute myeloid leukemia (AML) comprises a diverse group of blood cancers with varying genetic, phenotypic, and clinical traits, making development of targeted therapy challenging. Metabolic reprogramming in AML has been described as relevant for chemotherapy effectiveness. 3-Bromopyruvate (3-BP) is an anticancer agent that undermines energy metabolism of cancer cells. However, the effect of 3-BP in hematologic malignancies, such as AML, needs further investigation. Thus, we aimed to explore 3-BP as a chemo-sensitizing agent in AML. Different approaches of combining 3-BP with classical chemotherapy (daunorubicin and cytarabin) were tested in diverse AML cell lines. Cell sensitivity to the different drug combinations was analyzed by Trypan blue staining. The effect of pre-treatment with a non-toxic concentration of 3-BP was assessed on the AML cell metabolic profile (Western blot and immunofluorescence), mitochondrial activity (cytometry flow), and antioxidant capacity (colorimetric detection kit). KG-1 and MOLM13 cells showed increased sensitivity to chemotherapy (decreased EC 50 values) after exposure to a non-toxic concentration (5 μ M) of 3-BP. In both cell lines, 5 glucose consumption without changing extracellular lactate levels. 5 μ μ M 3-BP decreased M 3-BP treatment increased reactive oxygen species levels and decreased cell antioxidant capacity by depleting reduced glutathione levels in both KG-1 and MOLM13 cells. Our results demonstrate that non-toxic concentrations of 3-BP enhance the effect of classical chemotherapy in AML cells through a pro-oxidant mechanism. These data unveiled a new approach for AML treatment, using 3-BP or other pro-oxidant agents as co-adjuvants of chemotherapy, subsiding chemotherapy- induced side effects.
- Frequency of TERT promoter mutations in human cancersPublication . Vinagre, João; Almeida, Ana; Pópulo, Helena; Batista, Rui; Lyra, Joana; Pinto, Vasco; Coelho, Ricardo; Celestino, Ricardo; Prazeres, Hugo; Lima, Luís; Melo, Miguel; Rocha, Adriana Gaspar; Preto, Ana; Castro, Patrícia; Castro, Ligia; Pardal, Fernando; Lopes, José Manuel; Santos, Lúcio; Reis, Rui Manuel; Cameselle-Teijeiro, José; Sobrinho-Simões, Manuel; Lima, Jorge; Máximo, Valdemar; Soares, PaulaReactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.
- Satisfação profissional dos técnicos de radiologia no setor privado e no setor públicoPublication . Preto, Ana; Costa, Maria Alexandra; Martins, HelenaA satisfação profissional é um tema atual, sendo alvo de diversas investigações, devido a este ter sido reconhecido como parte integrante nos cuidados de saúde como indicador de qualidade. De acordo com Spector (1997), a satisfação profissional pode ser explicada como medida no qual o trabalhador gosta do seu trabalho (satisfação profissional) ou não gosta do ser trabalho (insatisfação profissional). No entanto devido a conjuntura socioeconómica em que o país se encontra, e as constantes alterações vigentes no setor da saúde, parece fundamental avaliar as consequências destas alterações na satisfação profissional dos profissionais da saúde. Delineou-se este estudo, não experimental, descritivo e transversal com o objetivo principal de comparar e avaliar os níveis de satisfação profissional dos Técnicos de Radiologia a exercer funções no setor privado e público. Analisou-se também a relação da satisfação profissional com algumas variáveis sociodemográficas, nomeadamente a idade, género, remuneração e a experiência profissional. Para a recolha dos dados utilizou-se o questionário Minnesota Satisfaction Questionnaire-short version (Martins, 2012), sendo divulgado através de um inquérito on-line. No estudo participaram 110 técnicos de radiologia a nível nacional (40 a exercer funções no setor privado e 42 a exercer funções no setor público). Os resultados do presente estudo evidenciaram uma ligeira satisfação profissional (na autonomia, realização profissional, ambiente e chefia) nos técnicos de radiologia. Os técnicos de radiologia a exercer funções no setor público apresentam uma maior satisfação com a sua autonomia, que os técnicos de radiologia a exercer funções no setor privado. Foram evidenciadas correlações entre a satisfação profissional com a remuneração, a experiência profissional, a idade e o género. A escassez de estudos sobre a satisfação profissional dos técnicos de radiologia no setor privado e público é uma lacuna, fazendo deste estudo um estudo importante e revolucionário para direcionar novos estudos.
- Targeting lysosomes in colorectal cancer: exploring the anticancer activity of a New Benzo[a]phenoxazine derivativePublication . Ferreira, João C. C.; Granja, Sara; Almeida, Ana F.; Baltazar, Fátima; Gonçalves, M. Sameiro T.; Preto, Ana; Sousa, Maria JoãoColorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interest ing agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.