RESUMO
Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS(61K) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.
Assuntos
Melanócitos/patologia , Células-Tronco Neoplásicas/patologia , Sequência de Aminoácidos , Animais , Proliferação de Células/fisiologia , Senescência Celular/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Xenoenxertos , Humanos , Técnicas In Vitro , Melanócitos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Células-Tronco Neoplásicas/metabolismo , Nevo/metabolismo , Nevo/patologia , Transdução de SinaisRESUMO
The 2010 Deepwater Horizon oil spill impacted the northern Gulf of Mexico (GOM) during the spring spawning season of Atlantic bluefin tuna (BFT). Overlap between BFT spawning habitat and surface oil in the northern GOM was examined using satellite-derived estimates of oil coverage, and spawning habitat models. Results suggested that although eggs and larvae were likely impacted by oil-contaminated waters in the eastern GOM, high abundances of larvae were located elsewhere, especially in the western GOM. Overall, less than 10% of BFT spawning habitat was predicted to have been covered by surface oil, and less than 12% of larval BFT were predicted to have been located within contaminated waters in the northern GOM, on a weekly basis. Our results provide preliminary but important initial estimates of the effects of the spill on larval BFT mortality, as concern continues over the appropriate management responses to impacts of the spill.
Assuntos
Ecossistema , Monitoramento Ambiental , Poluição por Petróleo/análise , Reprodução , Atum/fisiologia , Poluentes Químicos da Água/análise , Animais , Clorofila/análise , Golfo do México , Dinâmica Populacional , Comunicações Via Satélite , Água do Mar/química , Movimentos da ÁguaRESUMO
Patients undergoing thoracic surgery are threatened by pulmonary complications such as pneumonia and atelectasis. Age, preoperative FEV(1), operative time and extent of resection are predictors for adverse outcome. Reported morbidity after lung resection is as high as 42% and mortality up to 7%. Fast track in thoracic surgery aims at reducing morbidity and mortality rates after lung resection by introducing specific measures into the pre-, intra- and postoperative periods. Basic fast track elements in thoracic surgery are smoking cessation, preoperative physiotherapy, micronutrient supplementation, high thoracic epidural anesthesia, fluid restriction, early mobilization and enteral feeding. The effectiveness of these individual measures has been proven of value in perioperative care, however, evidence on multimodal therapy regimens in thoracic surgery is limited. In particular it remains to be elucidated which patients should be fast tracked in order to improve outcomes.
Assuntos
Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Torácicos , Redução de Custos/economia , Deambulação Precoce , Medicina Baseada em Evidências/economia , Alemanha , Humanos , Tempo de Internação/economia , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Assistência Perioperatória/economia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/mortalidade , Taxa de Sobrevida , Procedimentos Cirúrgicos Torácicos/economia , Procedimentos Desnecessários/economiaRESUMO
BACKGROUND: Mediastinal lymph node staging is essential to determine treatment options in patients with NSCLC. Positron emission tomography (PET) detects increased glucose uptake in malignant tissue using the glucose analogue 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS: In the present study were evaluated 155 patients with focal pulmonary tumors who underwent both preoperative computed tomography (CT) and FDG-PET scanning (116 malignant and 39 benign lesions). RESULTS: Findings in 155 patients included 116 malignant and 39 benign lesions. For N-staging, FDG-PET showed a sensitivity of 88%, a specificity of 91%, and an accuracy of 89%. Corresponding figures for CT were 77%, 76%, and 77%, respectively. CONCLUSIONS: FDG-PET is an effective, noninvasive method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to operability, FDG-PET could differentiate reliable between patients with N1/N2 disease and those with unresectable N3 disease.