Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT

Erythropoietin receptor (EPOR) is widely expressed in healthy and malignant tissues. In certain malignancies, EPOR stimulates tumor growth. In healthy tissues, EPOR controls processes other than erythropoiesis, including mitochondrial metabolism. We hypothesized that EPOR also controls the mitochondrial metabolism in cancer cells. To test this hypothesis, we generated EPOR-knockdown cancer cells to grow tumor xenografts in mice and analyzed tumor cellular respiration via high-resolution respirometry. Furthermore, we analyzed cellular respiratory control, mitochondrial content, and regulators of mitochondrial biogenesis in vivo and in vitro in different cancer cell lines. Our results show that EPOR controls tumor growth and mitochondrial biogenesis in tumors by controlling the levels of both, pAKT and inducible NO synthase (iNOS). Furthermore, we observed that the expression of EPOR is associated with the expression of the mitochondrial marker VDAC1 in tissue arrays of lung cancer patients, suggesting that EPOR indeed helps to regulate mitochondrial biogenesis in tumors of cancer patients. Thus, our data imply that EPOR not only stimulates tumor growth but also regulates tumor metabolism and is a target for direct intervention against progression

ORIGEM DA ENFERMAGEM PEDIATRA MODERNA

Este estudo tem por objetivo analisar a origem da enfermagem pediatra moderna intitucionalizada em meados do século XIX tomando-se o conhecimento como instrumento de apreensão do objeto de trabalho pelo homem. De uma perspectiva histórica, a enfermagem é entendida como prática socialmente articulada, parte de um processo coletivo de trabalho, cujas finalidades são o controle da doença na sociedade a nível coletivo e a recuperação individual da força de trabalho. Mediante bibliografia selecionada, procura-se identificar as características da assistência de enfermagem à criança na Inglaterra, no século XIX e os movimentos sumultâneos da prática médica: Medicina Social, Prática Médica Clínica e Puericultura. A seguir, são analisadas as características da assistência à criança nos Estados Unidos na primeira metade deste século e o seu referencial teórico.The object of study of this investigations in the knowledge in pediatrics nursing from the institutionalization of the modern nursing beginning from the XIX Century. The knowledge in this study is considered as an instrument from which man apprehends his working object. From an historical perspective nursing is seen as a social articulated pratice, as part of a collective process of works, whose purposes are: the control of the disease in the society, based on collective level and the recuperation of the individual working strenght. Through the bibliography, we try to identify the characteristics of children's nursing assistance in England, during the XIX Century and the simultaneous movements of the medicinal practice: the social medicine, the clinic medical practice and puericulture. Followed the characteristics of the children's assistance in the United States in the beginning of the century and the theoretical reference in wich it is locate