Combined administration of a small-molecule inhibitor of TRAF6 and Docetaxel reduces breast cancer skeletal metastasis and osteolysis:Running title : TRAF6/NFkB inhibition reduced breast cancer metastasis

Tumour necrosis factor receptor-associated factor 6 (TRAF6) has been implicated in breast cancer and osteoclastic bone destruction. Here, we report that 6877002, a verified small-molecule inhibitor of TRAF6, reduced metastasis, osteolysis and osteoclastogenesis in models of osteotropic human and mouse breast cancer. First, we observed that TRAF6 is highly expressed in osteotropic breast cancer cells and its level of expression was higher in patients with bone metastasis. Pre-exposure of osteoclasts and osteoblasts to non-cytotoxic concentrations of 6877002 inhibited cytokine-induced NF\u3baB activation and osteoclastogenesis, and reduced the ability of osteotropic human MDA-MB-231 and mouse 4T1 breast cancer cells to support bone cell activity. 6877002 inhibited human MDA-MB-231-induced osteolysis in the mouse calvaria organ system, and reduced soft tissue and bone metastases in immuno-competent mice following intra-cardiac injection of mouse 4T1-Luc2 cells. Of clinical relevance, combined administration of 6877002 with Docetaxel reduced metastasis and inhibited osteolytic bone damage in mice bearing 4T1-Luc2 cells. Thus, TRAF6 inhibitors such as 6877002 - alone or in combination with conventional chemotherapy - show promise for the treatment of metastatic breast cancer

Todas as criaturas do mundo: a arte dos mapas como elemento de orientação geográfica

Vague in the outlines and abounding in figures of real or fabulous creatures, the iconography of medieval maps played a significant role in helping users to recognize lands that were virtually unknown to Christendom. In a world with no reliable latitudes and longitudes, the land contours, inhabitants and even certain elements of fauna and flora could become variables of utmost importance for geographic orientation. Notwithstanding the higher levels of precision achieved in their efforts to represent geographic space, the considerable advancements made in latitude determination, and their continuous pursuit of a practical method for the establishment of longitudes, the cartographers of the Age of Discoveries still went to the trouble of depicting notable elements - whether real or imaginary - to help travelers get their bearings around different regions of the globe. As the presence of Europeans continued to expand and an authentic scientific revolution took place in the 17th century, the lengthy notes and eye¿catching representations of nature and local inhabitants soon lost their utility as points of reference on 17th-century maps to become mere accessories of aesthetic and commercial value. The advent of the 18th century consolidated, once and for all, the transformation of such illustrations into essentially decorative elements with no other relevant role to play in mapmaking. In addition to decreasing in number, the figures became more stylized and moved to the borders of the maps as ornamental motifs. Although they often maintained some sort of relation with the geographic space depicted on the map, the motifs chosen could also constitute a rather independent element. In fact, allegories, compositions with a variety of mythological figures, and historical representations were often used to underscore the power of certain political agents

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema