ABSTRACT
OBJECTIVE@#To detect the expression of miR-126 in different tissues and organs and the change of peripheral blood glucose in microRNA-126 knock down (miR-126 KD) mouse, and to explore the pathological significance.@*METHODS@#Total RNAs were isolated from twelve kinds of tissues and organs in wild-type mouse (WT) and miR-126 KD mouse respectively. Th en, the expression level of miR-126 was detected by real-time PCR assay. Th e levels of peripheral blood glucose and body weight of miR-126 KD mice were measured. Th e pathologic changes of pancreas and lung tissue were observed by HE staining.@*RESULTS@#Compared with the WT mice, the relative expression of miR-126 in spleen, liver, muscle and lung from the miR-126 KD mice were dramatically decreased respectively (P<0.05). The level of peripheral blood glucose in the miR-126 KD mouse increased significantly at seven week and sixteen week after the birth (P<0.05). HE staining showed that the pathological structure of pancreas and liver were abnormal. The body weight of miR-126 KD mice was increased obviously from thirteen week after birth (P<0.05).@*CONCLUSION@#Peripheral blood glucose levels in the miR-126 KD mouse were dramatically elevated, which might be related to the pathological changes in the structure of pancreas and liver. These results suggest that miR-126 may play an important role in the metabolism of blood glucose and the development of type 2 diabetes mellitus.
Subject(s)
Animals , Mice , Blood Glucose , Body Weight , Diabetes Mellitus, Type 2 , Gene Knockdown Techniques , Liver , Pathology , MicroRNAs , Genetics , Pancreas , Pathology , Real-Time Polymerase Chain ReactionABSTRACT
Objective To investigate the effects of wet hyperthermia combined with microwave ablation on the pro-portion and function of CD 4 +CD25 +regulatory T cell in animal model of mouse mammary carcinoma and explore its significance .Methods An experimental model of mouse mammary carcinoma was established and then treated with microwave ablation on day 14.Local wet hyperthermia was also performed .The proportion of CD4 +CD25 +regula-tory T cells (Tregs) in splenocytes was analyzed by FACS.The relative expression of Foxp3, as well as the expres-sion of CTLA-4 and GITR, on Tregs was determined by real-time PCR assay and FACS respectively .Moreover, the secretion of TGF-βand IL-10 from Tregs also were detected by ELISA .In addition , the suppressive capacity of Tregs on CD4 +CD25 -T cell was also examined by MTT assay .Results The proportion of Tregs in wet hyperther-mia combined with microwave ablation treated group decreased significantly compared with that in wet hyperthermia or microwave ablation treated alone group ( P<0.05 ) .Moreover , the expression level of Foxp 3 on Tregs decreased significantly (P<0.05).Furthermore, the expression of CTLA4 and GITR, as well as the secretion of TGF-βand IL-10, on Tregs also obviously decreased (P<0.05).Finally, the suppressive capacity of Tregs on the proliferation of CD4+CD25-T cells were also significantly impaired ( P<0.05) .Conclusions Wet hyperthermia combined with microwave ablation os more effective than single wet hyperthermia or microwave ablation as a mono -therapy alone on the function of Tregs , which may be closely related to the enhanced suppression of tumor growth .
ABSTRACT
Objective To investigate the therapeutic effects of microwave ablation combined with dendritic cell (DC) tumor vaccine on a murine breast cancer model and to explore its immunological mechanism.Methods Forty-eight Balb/c mice were used to establish models of mouse mammary carcinoma,and then randomly divided into a sham-operation group,a microwave ablation treated group,a DC tumor vaccinated group and a microwave ablation plus DC tumor vaccinated group.Microwave ablation was conducted with the microwave ablation group on day 14 after establishing the model.DC tumor vaccination was performed on day 7 in the vaccinated group.In the microwave ablation plus DC tumor vaccinated group,DC tumor vaccination and microwave ablation were consecutively performed on days 7 and 14,respectively.Tumor growth,lung metastasis and survival were observed.The proportion of CD3+ and CD4+ T cells in splenocytes were analyzed by fluorescence Activated Cell Sorter (FACS) on the 14th day after microwave ablation.Serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were also detected using ELISA.Results The survival time (56.4 ± 4.3 days),tumor size (67.3 ± 6.1 mm2) and lung metastasis index (0.6 ± 0.4) in the microwave ablation plus DC tumor vaccinated group were all significantly lower than the corresponding averages in the microwave ablation and DC tumor vaccinated group.The proportions of splenic CD3 + T cells (27.8 ±10.3 ％) and CD4+ T cells (16.7 ± 8.3 ％) in the microwave ablation plus DC tumor vaccinated group were significantly larger than in the control group.Average serum levels of IFN-γ (41.8 ± 22.9 pg/ml) in the microwave ablation plus DC tumor vaccinated group were also significantly larger than in the control group,while the average serum level of IL-4 (15.4± 6.4 pg/ml) was significantly lower.Conclusions Microwave ablation and DC tumor vaccination together could have synergistic effects in treating experimental breast cancer,which might be closely related to the enhanced immune response.