ABSTRACT
Objective To investigate the expression of macrophage migration inhibition factor (MIF) and cell cycle regulating factor Cyclin D1 in hepatocellular carcinoma tissue and the interaction between MIF and Cyclin D1 in hepatocellular carcinoma cell cycle controlling. Methods Using quantitative real-time PCR and Western blotting to detect mRNA and protein expression of MIF and Cyelin DI in HCC tissues and tumor adjacent tissues. Specific small interfering RNA(siRNA) targeting MIF gene was transfccted at doses of 50 nmol/L and 100 nmoL/L into HCC cell lines of PLC and HepG2 with lipofeetamine 2000 methods to knockdown the expression of M1F gene and to investigare the the interaction between M1F and Cyclin D1. Results MIF and Cyclin D1 protein and mRNA were overexpressed in HCC tumor tissues. The relative expression of MIF,Cyclin D1 protein and mRNA were 0.825±0.13,0.843± 0.104 and 7.31±1.85 folds、4.27±1.05 folds, compared with the tumor adjacent tissues (FMIF= 15.5, P<0.01;FCyclin D1=87.5,P <0.01). In MIF siRNA treated PLC and HepG2 cells, MIF mRNA down regulation 71.2%±7.2%, 87.4%±2.9% ,74.3%±8.9% and 88.4%±4.6% respectively (FPLC = 315.5 ,P < 0.01 ; FHepG2= 201.2 P < 0.01). While MIF protein expression were significandy reduced to 0.33±0.03,0.11±0.02, 0.81±0.08 and 0.36±0.02 in a dose-dependent manner (FPLC= 43.9, P <0.01 ;FHepG2 = 133.4 P <0.01). Cyclin D1 mRNA was significantly down-regnlated in MIF siRNA treated PLC and HepG2 cell lines when compared with control group(P <0.01). In 50 nmol/L and 100 nmol/L groups, Cyclin DI mRNA levels were respectively decreased by 68.2%±3% and 78.1%±1.4% in PLC cell, 65.8%±4.7% and 77.3%±2.6% in HepG2 cell (FPLC= 1569, P < 0.01 ; FHepG2= 480.4, P <0.01). Compared with control groups, Cyclin D1 protein levels significantly reduced to 0.28±0.06、0.15±0.03 and 0.44 ±0.04、0.13±0.02 in the PLC and HepG2 after M IF siRNA treatment(FPLC= 35.5, P < 0.01 ; FHepG2 = 114.7, P < 0.01). Conclusions MIF and Cyclin D1 mRNA and protein were overexpressed in HCC tumor tissues and participated in tumor cell cycle regulation. MIF may up-regnlate the expression of Cyclin DI via ERK signalling and precipitate in carcinogenesis of hepatocellular carcinoma.
ABSTRACT
BACKGROUND: Subsequent to liver transplantation, pulmonary infection and new drug resistant strain frequently appear due to complex pathophysiological changes and abuse of antibiotics.OBJECTIVE: To collect the clinical data of 6 cases who underwent liver transplantation, and analyze the prevention and treatment measures of pulmonary infection after liver transplantation.DESIGN, TIME AND SETTING: Retrospective case analysis, performed in the Department of Hepatobiliary Surgery,First People's Hospital of Guangzhou between January and December 2004.PARTICIPANTS: Six cases that underwent liver transplantation and received treatment in the First People's Hospital of Guangzhou were recruited in the present study. All 6 cases underwent selective homologous whole liver transplantation, 5cases underwent modified orthotopic piggyback liver transplantation, and only 1 underwent classical orthotopic liver transplantation.METHODS: The clinical data of the 6 cases were retrospectively analyzed. After transplantation, basic disinfection,isolation, infection-protection measures should be taken. In addition, etiological information was collected. Chest X-ray was underwent to know the lung at the early stage. Aseptic manipulating was strictly performed during sputum aspiration.Gastrointestinal decompression and non-obstructed drainage were maintained to prevent aspiration. Moreover, preventive anti-infective treatment against the bacteria, fungi, and viruses was performed.MAIN OUTCOME MEASURES: Pulmonary infection and curative effects subsequent to liver transplantation.RESULTS: Of the 6 cases, 5 presented with pulmonary infection, including 1 at 4-11 days after transplantation and 1 at 1day after transplantation. One case died of respiratory failure. The remaining 5 cases were cured after standardized anti-infection, respiratory therapy, sputum aspiration, and nutritional support.CONCLUSION: Application of effective antibiotics, aseptic operation in sputum aspiration, and unobstructed respiratory tract drainage are important measures for treating pulmonary infection subsequent to liver transplantation.