RESUMO
BACKGROUND: Our previous proteomic analysis revealed that mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein (MAWBP) were downregulated in gastric cancer (GC) tissues. These proteins interacted and formed complexes in GC cells. To investigate the role of MAWD and MAWBP in GC differentiation, we analyzed the relationship between MAWD/MAWBP and clinicopathologic characteristics of GC tissues and examined the expression of E-cadherin and pepsinogen C (PGC)-used as gastric mucosa differentiation markers-in MAWD/MAWBP-overexpressing GC cells and xenografts. METHODS: We measured MAWD, MAWBP, transforming growth factor-beta (TGF-beta), E-cadherin, and PGC expression in 223 GC tissues and matched-adjacent normal tissues using tissue microarray and immunohistochemistry (IHC) analyses, and correlated these expression levels with clinicopathologic features. MAWD and MAWBP were overexpressed alone or together in SGC7901 cells and then E-cadherin, N-cadherin, PGC, Snail, and p-Smad2 levels were determined using western blotting, semiquantitative RT-PCR, and immunofluorescence analysis. Alkaline phosphatase (AKP) activity was measured to investigate the differentiation level of various transfected cells, and the transfected cells were used in tumorigenicity assays and for IHC analysis of protein expression in xenografts. RESULTS: MAWD/MAWBP positive staining was significantly lower in GC tissues than in normal samples (P < 0.001), and the expression of these proteins was closely correlated with GC differentiation grade. Kaplan-Meier survival curves indicated that low MAWD and MAWBP expression was associated with poor patient survival (P < 0.05). The differentiation-related proteins E-cadherin and PGC were expressed in GC tissues at a lower level than in normal tissues (P < 0.001), but were upregulated in MAWD/MAWBP-overexpressing cells. N-cadherin and Snail expression was strongr in vector-expressing cells and comparatively weaker in MAWD/MAWBP co-overexpressing cells. MAWD/MAWBP co-overexpression inhibited Smad2 phosphorylation and nuclear translocation (P < 0.05), and AKP activity was lowest in MAWD/MAWBP coexpressing cells and highest in vector-expressing cells (P < 0.001). TGF-beta, E-cadherin, and PGC expression in xenograft tumors derived from MAWD/MAWBP coexpressing cells was higher than that in control. CONCLUSIONS: MAWD and MAWBP were downregulated and associated with the differentiation grade in GC tissues. MAWD and MAWBP might induce the expression of differentiation-related proteins by modulating TGF-beta signaling in GC cells.
Assuntos
Proteínas de Neoplasias/genética , Proteínas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Biomarcadores , Caderinas/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Prognóstico , Mapas de Interação de Proteínas , Proteínas/metabolismo , Proteínas de Ligação a RNA , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Fator de Crescimento Transformador beta/metabolismoRESUMO
Cardiopulmonary resuscitation (CPR) is series of rescue measures for saving cardiac arrest patients. Early initiation and good quality of CPR is crucial for increasing chance of survival from out-of-hospital cardiac arrest. In recent years, the CPR guidelines have changed a lot, especially in basic life support. The guideline now pays more attention on chest compression and less to ventilation. CPR with chest compression only and without mouth-to-mouth ventilation is more popular. In this article, we outline the development and recent researches of CPR. As depriving oxygen from a collapsed patient for 6 min may result in poor outcome, the average time for ambulance transport is longer (about 10 to 16 min) in China, which makes rescuers easy to feel fatigue, chest compression only CPR is not suitable in China. Though non-professional rescuers have difficulty to perform mouth-to-mouth ventilation, they generally show a willingness to do so. To strengthen public standard CPR training including mouth-to-mouth ventilation and chest compression, is most important to promote CPR in China.