ABSTRACT
Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p < 0.01; p < 0.01), contrasting with a decrease in C3948 (p < 0.001; p < 0.05), with mild effects in T238 migration (p < 0.01) and C643 invasion (p < 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p < 0.05) and C3948 (p < 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α; p < 0.05) in C3948-macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture. SPRY4 silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness. SPRY4 is a possible modulator of macrophage-ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes.
ABSTRACT
Medard Boss é considerado fundador da Daseinsanalyse. Conquanto a relevância de seu legado para a psicologia, sua obra é pouco conhecida na comunidade científica brasileira. Esta pesquisa, no intento de descobrir o que e como se tem referenciado o daseinsanalista, orienta-se por uma revisão integrativa da literatura de artigos científicos, indexados em portais abertos e gratuitos, que citem Medard Boss. Foram eleitas palavras-chave, então aplicadas em três bancos de dados (SciELO, PePSICe Lilacs). Após seleção por critérios de exclusão, chegou-se a um Nfinal de 37 publicações. Dos resultados, percebe-se que Boss é pouco referenciado pelos artigos brasileiros. Quando lembrado, a maior parte das menções é breve. Uma minoria de autores concentra a maior parte das publicações. Apenas dois livros de Boss estão traduzidos para o português. Vinte e sete porcento dos artigos que remetem ao daseinsanalista não usam nenhuma referência de sua obra.
Medard Boss is the founder of Daseinsanalyse. Despite the relevance of his legacy to psychology, his theory is little known by the Brazilian scientific psychological community. This research, with the aim of understanding how and what aspects of the daseinsanalist is referenced, is oriented by an integrative review of the literature of scientific articles indexed on open and free portals that cite Medard Boss. Keywords were chosen, which were applied in three databases (SciELO, PePSICand Lilacs). After selection by exclusion criteria, it has provided a final N of 37 publications. In the results, it is concluded that Medard Boss is little referenced by Brazilian articles. When he is remembered, most of the mentions are brief.A minority of authors concentrate most publications. Only three of Boss books are translated to Portuguese, while 27% of the articles that refer to the daseinsanalist do not use any reference of his work.
Subject(s)
Psychology , Existentialism/psychologyABSTRACT
The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.
ABSTRACT
Ewing's Sarcoma (ES) is the second most frequent malignant bone tumour in children and young adults and currently only untargeted chemotherapeutic approaches and surgery are available as treatment, although clinical trials are on-going for recently developed ES-targeted therapies. To study ES pathobiology and develop novel drugs, established cell lines and patient-derived xenografts (PDX) are the most employed experimental models. Nevertheless, the establishment of ES cell lines is difficult and the extensive use of PDX raises economic/ethical concerns. There is a growing consensus regarding the use of 3D cell culture to recapitulate physiological and pathophysiological features of human tissues, including drug sensitivity. Herein, we implemented a 3D cell culture methodology based on encapsulation of PDX-derived ES cell spheroids in alginate and maintenance in agitation-based culture systems. Under these conditions, ES cells displayed high proliferative and metabolic activity, while retaining the typical EWSR1-FLI1 chromosomal translocation. Importantly, 3D cultures presented reduced mouse PDX cell contamination compared to 2D cultures. Finally, we show that these 3D cultures can be employed in drug sensitivity assays, with results similar to those reported for the PDX of origin. In conclusion, this novel 3D cell culture method involving ES-PDX-derived cells is a suitable model to study ES pathobiology and can assist in the development of novel drugs against this disease, complementing PDX studies.
ABSTRACT
La campaña de difusión del índice ultravioleta se ha desarrollado durante el año 2005 en forma casi rutinaria, y se continúa con la difusión del índice haciendo énfasis en los riesgos que se tienen durante esta época de verano; en esta gestión, se ha añadido Rdio Francia a los medios que reportan el valor del IUV que se les proporciona
