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Objective To detect the expressions of Matrix Metalloprotein-11 ( MMP-11 ) and Cathepsin-D(Cath-D),and investigate their relationship and prognostic significance. Methods The study included 95 cases′ clinical date and postoperative specimens of gastric adenocarcinoma ( North China University of Science and Technology Affiliated Hospital,2010. 01-2013. 12) as observation group,70 cases of normal gastric tissue(from observation group) as control group. Expressions of MMP-11 and Cath-D were detected by IHC methods in two groups. Results The positive rate of MMP-11 was 51. 6%( 49/95) in observation group,5. 7%(4/70)in control group(χ2＝38. 884,P＜0. 05). The positive rate of Cath-D was 73. 7%(70/95) in observation group,28. 6%(20/70) in control group(χ2＝33. 082,P＜0. 05). The positive rate of MMP-11 was correlated with metastasis and vascular invasion(χ2＝7. 193、15. 566,P＜0. 05). The positive rate of Cath-D was correlated with maximal diameter,lymph node metastasis,vascular invasion and proliferation index(χ2＝7.431、5.654、6.569、6.801,P＜0.05).There was positive relationship between MMP-11 and Cath-D in observation group(r＝0. 46,P＜0. 05). The expressions of MMP-11 and Cath-D were correlated with prognosis in gastric adenocarcinoma ( P＜0. 05) . Conclusion The higher expressions and synergistic effect of MMP-11 and Cath-D may promote the occurrence and development in gastric adenocarcinoma. The joint detection of MMP-11 and Cath-D may be helpful to predict the prognosis of gastric adenocarcinoma.
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Objective To observe the expression of PD-L1 in breast cancer tissue and to investigate its correlation with cellu-lar immunity.Methods One hundred and fourteen paraffin-embedded specimens of breast cancer were collected from the Qian′an Municipal People′s Hospital.The expression of PD-L1 in breast tumor tissue was detected by immunohitochemical technique,then the relationship between PD-L1 expression and tumor clinicopathological characteristics was analyzed;the levels of peripheral blood CD3+,CD3+CD4+,CD3+CD8+,CD3-CD19+,CD3-CD16+CD56+cells and CD4+/CD8+in the patients with PD-L1 negative and PD-L1 positive of the two groups were detected by the flow cytometry.Results Among 114 cases of breast cancer specimen,35 ca-ses(30.7%)were PD-L1 expression positive with the expression rate of 30.7%.The PD-L1 expression was correlated with the tumor size,histological grade and Ki-67 high expression(P<0.05);the cellular immunity status in the patients with PD-L1 negative expression was better than that in the patients with PD-L1 positive expression(P<0.05).Conclusion The PD-L1 expression is closely correlated with the poorer clinicopathological characteristics of breast cancer,its mechanism may be correlated with the dis-ruption of cellular immunity in the patients with PD-L1 positive expression.
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AIM:To investigate the role of high glucose in primary hepatocytes of mice fed with a high fat di-et.METHODS:Male C57BL/6J mice were fed a high fat (45%of calories) diet ad libitum for 6 weeks to induce hepatic steatosis.Primary hepatocytes were isolated from the mouse liver by the 2 step collagenase perfusion method .The cells were incubated in low glucose ( 5 mmol/L ) , low glucose plus mannitol ( 30 mmol/L ) , or high glucose ( 35 mmol/L ) DMEM medium for 12 h.The cell viability , apoptosis , mitochondrial membrane potential , and caspase enzymatic activities were measured.Furthermore, proteins related to the stress-sensitive signaling pathway of regulating high glucose-induced apoptosis in primary hepatocytes were determined by Western blotting .RESULTS:Incubation with 35 mmol/L glucose re-sulted in a significant decrease in cell viability and an increase in apoptosis , whereas mannitol had no significant effect on the cell viability or apoptosis .A progressive depolarization of the mitochondria , an increase in cytosol cytochrome C and a dramatic decrease in mitochondrial cytochrome C in high-glucose stressed hepatocytes were observed .The enzymatic activi-ties of caspase-9 and caspase-3, but not caspase-8, were significantly increased in high glucose-stressed hepatocytes ( P<0.05).High glucose treatment suppressed the expression of Bcl-2 and Bcl-xL, while it increased the expression of the pro-apoptotic factor Bax .CONCLUSION:High glucose stress reduces mitochondrial membrane potential , initiates mitochon-dria-mediated apoptotic pathways and promotes apoptosis of hepatocytes with steatosis .This may be an important pathologi-cal mechanism of hyperglycemia-induced progression of nonalcoholic fatty liver disease .
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AIM: To study the role of c-Jun NH_2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-α (TNF-α) or H_2O_2 in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125, then exposed to 1 nmol/L of TNF-α or micromolar H_2O_2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS: Compared to control adipocytes, 12 h incubation with TNF-α or H_2O_2 led to 50%-55% reduction (P<0.01) of the insulin-dependent glucose uptake. JNK1 siRNA transfection significantly inhibited JNK1 expression and blocked the TNF-α or H_2O_2-induced impairments of cellular glucose uptake. Pretreatment with SP600125 (20 μmol/L) resulted in significant increases in insulin-stimulated glucose uptakes in both TNF-α (66%) and H_2O_2 (62%) treated adipocytes (P<0.01). CONCLUSION: JNK plays a key role in TNF-α or H_2O_2 induced insulin resistance in 3T3-L1 adipocytes, and inhibition of JNK over-activation may be a new therapeutic target for insulin resistance.
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AIM:To study the role of c-Jun NH2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-? (TNF-?) or H2O2 in 3T3-L1 adipocytes. METHODS:Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125,then exposed to 1 nmol/L of TNF-? or micromolar H2O2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS:Compared to control adipocytes,12 h incubation with TNF-? or H2O2 led to 50%-55% reduction (P