Long-term dexamethasone treatment increases the engraftment efficiency of human breast cancer cells in adult zebrafish.

The host immune system tends to reject xenogenic-implanted cells making tumor development in adult host animal models difficult. Immune system suppression is used for successful xenotransplantation of human cancer cells in many animal models. The studies of cancer development processes in vivo offer opportunities to understand cancer biology and discover new therapeutic strategies. In this context, zebrafish is a model that has been widely applied in the study of human diseases, such as cancer. However, the long-term immunosuppression of these adult zebrafish is still under study as a xenograft animal model for human cancer. This work aimed to evaluate the effects of 21 days of (long-term) exposure of dexamethasone in zebrafish-transplanted with MGSO-3 cells, human breast tumor cell line. Our results show that the animals, while kept on dexamethasone treatment, remained with a 50% reduction in the number of peripheral lymphocytes. In vitro data demonstrated that up to 7 days of dexamethasone treatment did not alter the morphology, proliferation, or viability of MGSO-3 cells. The animals that received a prolonged dexamethasone treatment allowed the engraftment of tumor cells in 100% of the zebrafish tested. These animals also showed tumor progression over 21 days. The experimental group that received only previous exposure to dexamethasone had their tumors regressed after 14 days. In conclusion, the prolonged use of dexamethasone in zebrafish showed a potential strategy for in vivo monitoring of xenograft tumor growth for development studies, as well as in anticancer drug discovery.

Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy.

The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 °C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%.

Alterações auditivas e fenilcetonúria: uma revisão sistemática / Hearing disorders and phenylketonuria: a systematic review

TEMA: a fenilcetonúria é uma doença genética que provoca alterações bioquímicas conduzindo a uma deficiência na síntese de proteínas e de neurotransmissores, e prejudicando o processo de mielinização. Mudanças estruturais e funcionais da mielina podem alterar os padrões de condutividade neuronal e ou diminuir a conexão sináptica em indivíduos com fenilcetonúria. Essencialmente, um tratamento dietético deve ser realizado dentro das primeiras semanas de vida para evitar as manifestações clínicas e bioquímicas da doença. Quando a dieta é mantida ininterruptamente, as crianças com fenilcetonúria apresentam desenvolvimento normal. Porém, foram observados déficits em funções executivas, na interação inter-hemisférica, na linguagem e memória mesmo em crianças com tratamento precoce e dieta adequada. Algumas pesquisas foram realizadas para investigação da relação entre fenilcetonúria e alterações auditivas. OBJETIVO: rever de forma sistemática os artigos científicos dedicados à pesquisa da relação entre alterações auditivas e hiperfenilalaninemias, destacando a fenilcetonúria clássica. As referências bibliográficas foram obtidas por meio de pesquisa nas bases de dados Lilacs, Medline, Biblioteca Cochrane e Scielo e por busca na lista de referência dos artigos identificados e selecionados. CONCLUSÃO: conclui-se que a relação entre hiperfenilalaninemias, incluindo a fenilcetonúria, e alterações auditivas ainda é controversa na literatura. Sugere-se a realização de mais investigações sobre a função auditiva nesses indivíduos a fim de elucidar essa possível relação.

BACKGROUND: phenylketonuria is a genetic disorder that causes biochemical alterations, leading to a deficiency in the synthesis of proteins and neurotransmitters and thereby hindering the myelination process. Structural and functional changes in myelin can alter neural conductivity patterns and or reduce synaptic connection in individuals with phenylketonuria. Essentially, a dietary treatment should be implemented in the first weeks of life in order to avoid clinical and biochemical manifestations of the disease. When diet is continually maintained, children with phenylketonuria show normal development. However, deficits in executive functions, interhemispherical interaction, language and memory have been observed even in children with early treatment and appropriate diet. Some researches were carried out for investigating the relationship between phenylketonuria and alterations in the hearing function. PURPOSE: to systematically review articles dedicated to the research of relationship between hearing disorders and hyperphenylalaninaemias, highlighting the classic phenylketonuria. The bibliographical references were obtained through research in the databases: Lilacs, Medline, Cochrane Library and Scielo and through search in the reference list of the identified and selected articles. CONCLUSION: the relationship among hyperphenylalaninaemias, including phenylketonuria, and hearing alterations is still controversial in the literature. It is suggested that more investigations as for the hearing function are necessary on those individuals in order to elucidate this possible relationship.