Inhibition Of Epithelial-mesenchymal Transition And Metastasis By Combined Tgfbeta Knockdown And Metformin Treatment In A Canine Mammary Cancer Xenograft Model

Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-β1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice’s lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-β1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-β1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-β1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-β1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-β1 silencing and their effect on EMT. © 2017, Springer Science+Business Media New York.221274

Cytotaxonomic and evolutionary considerations about karyotipic data of fishes from the Iguaçu River Basin in South of Brazil

The cytogenetic data available in the literature about the ichthyofauna of the Iguaçu River basin were analyzed in this review. The ichthyofauna was characterized by the high level of endemism and by the low diversity of species. Twenty-four of the eighty-one species were already karyotyped; six Characiformes, fourteen Siluriformes and four Perciformes. The chromosomal data showed the taxonomic and systematic complexity of the groups. Hypothesis related to the evolution of some Characiformes and Siluriformes groups from the Iguaçu River are proposed, as well as the utilization of karyotypic data for cytotaxonomy.<br>Nesta revisão são analisados os dados citogenéticos disponíveis na literatura relativos à ictiofauna da bacia do Rio Iguaçu, a qual é caracterizada pelo alto grau de endemismo e pela baixa diversidade de espécies. Das oitenta e uma espécies conhecidas, vinte e quatro já foram cariotipadas sendo 6 Characiformes, 14 Siluriformes e 4 Perciformes. Os dados cromossômicos evidenciam a complexidade taxonômica e sistemática dos grupos. São propostas hipóteses relacionadas à evolução de alguns grupos de Characiformes e Siluriformes do Rio Iguaçu, assim como o aproveitamento de dados cariotípicos para a citotaxonomia