OBJECTIVETo study the antitumor and distant bystander effects of cationic liposome-mediated cytosine deaminase (CD)/5-fluorocytosine (5-FC) suicide gene system combined with interferon-gamma (IFN-gamma) in vivo.

METHODSMurine hepatoma 22 (H22) cells transfected by CD gene were inoculated subcutaneous in Kunming mice in the left axillary region, and the H22 cells without CD gene transfection were inoculated in the right axillary region. The mice were randomly divided into 4 groups and treated with normal saline , 5-FC, IFN-gamma, and 5-FC+ IFN-gamma on a daily basis. The tumor inhibition and distant bystander effects were observed in the mice.

RESULTSExposure of CD gene-transfected tumor to 5-Fc resulted in obvious tumor growth inhibition with an inhibition rate of 78.38%, which was significantly increased to 93.21% (P<0.01) with 5-Fc +IFN-gamma treatment. A notable distant bystander effect in the CD/5-FC suicide gene system was observed in vivo, with a tumor inhibition rate of was 54.42%; when combined with IFN-gamma, the inhibition rate increased significantly to 87.57% (P<0.05).

CONCLUSIONWhen combined with IFN-gamma, CD/5-FC suicide system has stronger anti-tumor and distant bystander effects. CD/5-FC suicide gene system combined with IFN-gamma may provide a potential therapy for malignant tumors.

Animals ; Bystander Effect ; Cations ; chemistry ; Cytosine Deaminase ; genetics ; Flucytosine ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; methods ; Interferon-gamma ; therapeutic use ; Liposomes ; Liver Neoplasms, Experimental ; therapy ; Male ; Mice ; Random Allocation

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes