Hypoxia-induced immortalization of primary cells depends on Tfcp2L1 expression.

Cellular senescence is a stress response mechanism that induces proliferative arrest. Hypoxia can bypass senescence and extend the lifespan of primary cells, mainly by decreasing oxidative damage. However, how hypoxia promotes these effects prior to malignant transformation is unknown. Here we observed that the lifespan of mouse embryonic fibroblasts (MEFs) is increased when they are cultured in hypoxia by reducing the expression of p16INK4a, p15INK4b and p21Cip1. We found that proliferating MEFs in hypoxia overexpress Tfcp2l1, which is a main regulator of pluripotency and self-renewal in embryonic stem cells, as well as stemness genes including Oct3/4, Sox2 and Nanog. Tfcp2l1 expression is lost during culture in normoxia, and its expression in hypoxia is regulated by Hif1α. Consistently, its overexpression in hypoxic levels increases the lifespan of MEFs and promotes the overexpression of stemness genes. ATAC-seq and Chip-seq experiments showed that Tfcp2l1 regulates genes that control proliferation and stemness such as Sox2, Sox9, Jarid2 and Ezh2. Additionally, Tfcp2l1 can replicate the hypoxic effect of increasing cellular reprogramming. Altogether, our data suggest that the activation of Tfcp2l1 by hypoxia contributes to immortalization prior to malignant transformation, facilitating tumorigenesis and dedifferentiation by regulating Sox2, Sox9, and Jarid2.

[Primary cardiac lymphoma: cytological diagnosis and treatment with response to polychemotherapy and hematopoietic precursor autotransplant. Presentation of a case a review of the literature]. / Linfoma cardiaco primario: diagnóstico citológico y tratamiento con respuesta a poliquimioterapia y a autotrasplante de precursores hematopoyéticos. Presentación de un caso y revisión de la literatura.

The primary cardiac lymphoma (PCL) is an extremely infrequent tumor suffered by immunocompetent patients with a difficult diagnosis and slow progress leading to a serious prognosis and few therapeutically possibilities. It's a primary-cardiac non-Hodgkin's lymphoma (NHL) in a patient of 46-year-old, immunocompetent, who started with a congestive heart failure and atrial flutter. Some examinations were carried out such as a transesophageal echocardiography (TEE), a computed tomography (TC) and a magnetic resonance imaging (MRI) and an intracardiac tumor placed in the interauricular septum was detected. The diagnosis was based on a pleural fluid cytological examination. It was decided to follow a chemotherapy treatment and the autologous peripheral blood stem cells transplantation was carried out. The patient remains in full remission thirty-six months after diagnosis and twenty-nine months after the autotransplant. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate and aggressive antilymphoma therapy can thus help in obtaining a long survival in patients with PCL.

[Citrobacter freundii endocarditis]. / Endocarditis por Citrobacter freundii.

Infection by Citrobacter appears in man only in certain circumstances, since it usually acts as contaminant or colonizer. Bacteraemia by this bacillus can affect immunodeficient people, elderly people or those patients who have undergone invasive hospital processes. Although incidence of bacteraemia is low (0.3-0.9%), the death rate is very high, about 48%. This bacillus is seldom the cause of endocarditis. That is why we describe a case of endocarditis by Citrobacter freundii, in an aged person with previous valvulopathy.