Immunoexpressão das proteínas DEK e Fosfo-P38 no câncer retal antes da quimiorradioterapia / Immunoexpression of dek and phospho-p38 proteins in rectal cancer before chemoradiation therapy

ABSTRACT Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. Results: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). Conclusion: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.

RESUMO Contexto: O câncer colorretal é mundialmente, a terceira causa de câncer e um quarto destes estão localizados no reto. O oncogene DEK está envolvido em vários processos nucleares e pode acelerar a tumorigênese. Objetivo: Este estudo tem como objetivo avaliar a imunoexpressão das proteínas DEK e Fosfo-P38 antes da terapia neoadjuvante em pacientes com adenocarcinoma de reto e correlacioná-la com resposta clínica e sobrevida. Métodos: Foram incluídos pacientes com adenocarcinoma de reto médio e baixo submetidos à quimio e radioterapia seguida de ressecção cirúrgica do tumor. A expressão e quantificação foram estudadas por imuno-histoquímica nos tecidos de biópsia tumoral utilizando um sistema HScore. Escores ≥4 foram considerados positivos e aqueles com <4 negativos. Resultados: Foram incluídos 22 pacientes com média de idade de 63,55 anos (DP: ±13,49). O estágio clínico antes do tratamento era T3 em 72,7%, T4 em 18,2%, 31,8% eram N1, 50% N0 e todos M0. Após a quimio e radioterapia, 54,6% eram T3; 22,7% eram T2; 9,1% eram T1 e 13,6% T0. Entre os tumores, 22,7% foram positivos para DEK e 63,6% positivos para Phospho-P38. Houve uma correlação positiva para a imunoexpressão da proteína DEK e o estágio pTNM (P=0,011). A proteína fosfo-P38 não apresentou correlação com esses parâmetros. Pacientes com HScore negativo para DEK tiveram sobrevida média de 141,33 meses (IC95%: 112,41-170,25) e aqueles com HScore positivo tiveram sobrevida média de 25,10 meses (IC95%: 17,36-32,84) (P<0,001). Conclusão: Observou-se maior expressão de DEK em estágios avançados. Os pacientes que apresentaram expressão de DEK <4 tiveram maior sobrevida, sendo um fator de pior prognóstico.

REGUL ATORY EFFECT OF SIMVASTATIN ON MIDDLE/L ATE STAGES OSTEOGENIC DIFFERENTIATION OF BONE MARROW MESENCHYMAL STEM CELLS VIA p38MAPK PATHWAY / 中国修复重建外科杂志

OBJECTIVE: To investigate the regulatory effect of simvastatin on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) at middle/late stages by p38MAPK pathway under condition of osteoinductive environment.

Propofol attenuates aquaporin-4 over-expression through p38 pathway on ammonia-induced neocortical astrocyte in rats / 中国病理生理杂志

AIM:To investigate the effects of propofol on ammonia-induced neocortical astrocyte aquaporin-4 expression in rats and its mechanism. METHODS:Astrocytes were separated from newborn Sprague Dawley rats. Glial fibrillary acidic protein,the specific protein of astrocyte,was labeled by cell immunofluorescence method. The purity of astrocyte achieved to 95% was considered to be used in the study. Grouping:cultured astrocytes were randomly divided into 5 groups (n=3):normal control group (N); ammonia-incubated for 24 h group (NH_4Cl-24 h); p38 antagonist SB203580 (10 μmol/L) pretreated group (SB); propofol (10 μmol/L) pretreated group (P); solvent (DMSO) control group (C). SB203580,propofol and DMSO were pretreated for 30 min before astrocytes were exposed to NH_4Cl. Cell morphology was assessed by light microscopy. The expression of aquaporin-4; p38 and p-p38 were detected by Western blotting. RESULTS:Astrocytes were found significant swelling when exposed to 5 mmol/L NH_4Cl in NH_4Cl-24 h group compared to control group. Pretreatment with propofol and SB203580 decreased astrocyte swelling. No significant change in total p38 in all groups was observed (P>0.05) by Western blotting analysis,while the levels of p-p38 and AQP4 in group SB and group P were significantly decreased compared to group C and group NH_4Cl-24 h (P<0.05).CONCLUSION:The expression of AQP4 is regulated by p38 pathway. Propofol pretreatment down-regulates aquaporin-4 expression through preventing the ammonia-induced p38 phosphorylation.

Reaserch of culmonary inflammation in cardiopulmonary bypass / 中国免疫学杂志

Objective:The experiment researched relation between applying p38MAPK inhibitor(SB203580) and pulmonary injury during CPB.Methods:18 pigs randomly distributed three groups(n=6). We perfused the lung of the second group with SB203580 during CPB. The first group(n=6) and the second group(n=6) are control group. Lung samples were collected. Activated forms of P38 were measured by Western blot. Pulmonary injury was determined by histology. Tissue water percentage was measured. Pulmonary function was measured.Results:Phospho-P38 of the first group were increased compared with both the second group and the third group(P

Inhibition of p38 MAPK kinase enhances diallyl disulfide-induced apoptosis in human CNE2 cells / 中国药理学通报

AIM To investigate the effects of p38 MAPK signaling on diallyl disulfide ( DADS ) induced apoptosis in CNE2 cells. METHODS Morphological changes and quantification of apoptotic cells were determined under fluorescence microscope after a 24 h treatment of CNE2 by DADS. Cell viability was determined with MTT method. Apoptosis detection was taken to the cells on flowcytometry. The expression of phospho p38 MAPK was measured by Western blotting. RESULTS After treatment with DADS at 50～150 ?mol?L -1 for 24 h,DADS elicited typical apoptotic morphologic changes (chromatic condensation, nucleus fragmentation). The amount of apoptosis cells increased in a concentration dependent manner but cell cycle arrest did not at 50～150 ?mol?L -1 ,incubation of CNE2 with DADS for 24 h also induced phospho p38 MAPK expression in a concentration dependent manner. Interestingly, DADS induced apoptosis was markedly increased by preincubation with SB203580, a specific p38 MAPK inhibitor,and increased the expression of phospho p42/ p44 CCDPK in a concentration dependent manner. CONCLUSION DADS activates p38 MAPK,and phospho p38 MAPK signaling appears to play protective roles in DADS induced apoptosis in CNE2.