ABSTRACT
This study examined whether 1-methyl-tryptophan[1-MT,an indoleamine 2,3-dioxygenase(IDO)inhibitor]could reduce CD4+CD25+regulatory T cells(Tregs)proliferation and improve the anti-tumor efficacy of dendritic cells(DCs)pulsed with tumor cell lysate in the mice bearing pancreatic adenocarcinoma.The models of pancreatic adenocarcinoma were established in C57BL/6 mice by subcutaneous injection of Pan02 cells.Eight mice which were subcutaneously injected with PBS served as control.The expression of IDO was determined in tumor draining lymph nodes(TDLNs)and spleens of the murine pancreatic adenocarcinoma models.The prevalence of Tregs was measured in the TDLNs and spleens before and after 1-MT administration.The dendritic cells were pulsed with tumor cell lysate for preparing DC vaccine.The DC vaccine,as a single agent or in combination with 1-MT,was administered to pancreatic adenocarcinoma mice.The anti-tumor efficacy was determined after different treatments by regular observation of tumor size.The results showed that the levels of IDO mRNA and protein in tumor-bearing mice were significantly higher than those in the normal control mice.The percentage of Tregs in the spleen and TDLNs was also higer in tumor-bearing mice than in normal control mice(P<0.05).Foxp3 expression was significantly lower in the TDLNs and spleens of tumor-bearing mice administrated with 1-MT than that in normal control mice.Furthemore,in the mice that were administered 1-MT plus DC vaccine,the tumor was increased more slowly than in mice treated with DC vaccine or 1-MT alone,or PBS on day 36(P<0.01).Our results indicated that 1-MT may enhance anti-tumor efficacy of dendritic cells pulsed with tumor cell lysate by downregulating the percentage of Tregs.
ABSTRACT
This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α)expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells.PANC-1 cells were divided into three groups: Control group,insulin group and insulin+YC-1(a pharmacological inhibitor of HIF-1α)group in terms of different treatments.Cells in the insulin group or insulin+YC-1 group were treated with insulin(0.1,1,10 and 100 nmol/L)alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1,0.1,1,10 and 100μmol/L).HIF-1α mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively.Cell proliferation and invasion were measured by using growth curve and invasion assay,respectively.Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1α protein expression,and YC-1 could dose-dependently block this effect.However,neither insulin nor YC-1 altered HIF-1α mRNA levels in PANC-1 cells.Moreover,insulin could enhance the proliferation and invasion of PANC-1 cells,while YC-1 could weaken this effect.It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment.The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1αprotein.
ABSTRACT
The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion (Omegaven ) on systemic inflammatory response syndrome (SIRS) during the ini-tial stage of severe acute pancreatitis (SAP).In a prospective,randomized and controlled trial,60 pa-tients with SAP were randomized either to treat with conventional therapy (Con group,n=30) or conventional therapy plus intravenous supplementation with 0-3 fish oil emulsion 0.2 g/kg every day (FO group,n=30).The effects were analyzed by the SIRS-related indexes.The results showed that APACHE-II scores in FO group were significantly lower,and the gap increased much farther after the 4th day than those in Con group (P<0.05).Fluid equilibrium time became shorter markedly in FO group than in Con group (5.1±9.2 days vs 8.4±2.3 days).In FO group,SIRS scores were markedly duced,while IL-10 decreased markedly,most prominently between the 4th and 7th day,and the ratio euteral supplementation with ω-3 fish oil emulsion could efficiently lower the magnitude and persis-tence time of the SIRS,markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines,im-prove severe condition of illness and may provide a new way to regulate the SIRS.
ABSTRACT
A stable and reliable infected necrotizing pancreatitis (INP) model in rats was established in order to study the pathophysiological mechanism and pathological development rule of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. Coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium tanrocholate in combination with different con-centrations of E. Coli (103, 104, 105/mL, respectively) into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancre-atic tissue. The results showed that acute necrotizing panereatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. Coli into the pan-creatic duct and the positive rate of germ cultivation in group B was 0. The INP model was estab-lished in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h sur-vival rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 104/mL E. Coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might he that the hemorrhage and necrosis of pancreatic tissue in-duced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs.Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.