1.Effect of 5-Aza-2′-deoxycytidine on experimental lung metastasis of breast cance
Sandi SHEN ; Aiguo WU ; Zhi ZHAO
Chinese Journal of General Surgery 1994;0(05):-
Objective To investigate the effect of 5-Aza-CdR on experimental lung metastasis of breast cancer and the possible mechanisms.Methods MDA-MB-231 cells were divided into control group and 5-Aza-CdR-treated group.The mRNA expressions and promotor methylation status of BRMS1 and CXCR4 of the MDA-MB-231 cells were evaluated by SqRT-PCR and MSP respectively.Then,the MDA-MB-231 cells of control group and 5-Aza-CdR-treated group were injected into BALB/c nude mice through lateral tail veins,respectively.five weeks later,the mRNA abundance of the target gene HPRT and internal control gene GAPDH of the lung tissues from the mice were evaluated by FqRT-PCR.Results 5-Aza-CdR upgraded the BRMS1mRNA expression significantly than that in control group(0 versus 0.39?0.001,P0.05) and the status of unmethylated CXCR4 CpG island 1 in promotor were not changed significantly.The Ct values of HPRT and GAPDH in control and 5-Aza-CdR-treated groups were 24.75?1.55,16.19?0.69 versus 27.61?1.67,17.48?0.96 respectively,2-??Ct=0.34.The mRNA abundance of the HPRT was lower and there were fewer metastases in the lungs of 5-Aza-CdR-treated group compared with control group.Conclusions 5-Aza-CdR can activate tumor metastasis suppressor gene BRMS1 by demethylation mechanism,and thus,decreased the ability of breast cancer MDA-MB-231 cells for experimental metastasis to lungs.
2.Relations between CT perfusion parameters and degree of hepatic ischemia reperfusion injury in a rabbit model
Chengwei GUO ; Sandi SHEN ; Xianlin YI ; Zhonglin ZHANG ; Zaiyi LIU ; Changhong LIANG
Chinese Journal of Radiology 2011;45(11):1063-1067
Objective To observe the changes of hepatic CT perfusion parameters and their correlation with serum aspartate transaminase( AST),alanine transaminase(ALT) and alkaline phosphatase (ALP) in a rabbit hepalic ischemia reperfusion injury (IRI) model.Methods Hepatic IRI was produced in rabbits by inducing left liver lobe ischemia (60 min) followed by 6 h,12 h and 24 h reperfusion (6 rabbits were used for each reperfusion interval ).Additional 6 rabbits were served as sham-operatedcontrols.All the rabbits were scanned with a dynamic iCT protocol.Blood samples were taken from the superior mesenteric vein to measure the levels of serum amylase (ALT,AST,and ALP) in various groups,and liver samples were taken for histological examinations after scanning.One-way analysis of variance (ANOVA) was used to determine differences between groups.The correlations of CT perfusion parameters with serum levels were analyzed using Pearson correlation coefficient.Results Heterogeneity of CT perfusion patterns appeared in the 6 h groups,which presented as low enhanced area [ ( 25.1 ± 9.3 ) ml · 1min-1 · 100mg-1].In reduced perfusion regions of IRI group,HAP of 12 h IRI group [ ( 19.5 ± 13.6) ml · min-1 · 100 mg-1],24 h IRI group [(8.0+2.7) ml · min-1 · 100 mg-1 ],HPP of 6 h IRI group [(10.8±5.5) ml · min-1 · 100 rng-1],12 h IRI group [(14.4±5.2) ml · min-1 · 100 mg-1],24 h IRI group [(7.8±3.3) ml · min-1 · 100 mg-1] and TLP of 6 h IRI group [(35.9 ±14.0) ml ·min-1 · 100 mg-1 ],12 h IRI group [ (33.9 ± 16.1) ml · min-1 · 100 mg-1 ],24 h IRI group [ (16.0 ±5.5) ml · min- 1 · 100 mg-1 ] were lower than those of sham group [ HAP (21.2 + 10.5 ) ml · min-1100mg-1,HPP(63.5±24.0) ml · min-1 · 100 mg-1,TLP (81.4±24.8) ml · min-1 · 100 mg-1](F=8.376,25.950,16.925,P<0.01).However,HPI of 6 h IRI group [(65.9±3.9)%],12 h IRIgroup [ (54.2 ± 16.7)% ],and 24 h IRI group [ (48.9 ± 10.0)% ] were higher compared to sham group [ ( 24.1 ± 7.5 ) % ] ( F =43.664,P < 0.01 ).But,the perfusion parameters in the relatively normal area of IRI groups showed decline compared with sham group.The levels of AST,ALT and ALP in IRI groups were significantly higher than those in the sham group ( P <0.05).In poorly enhancing tissues,TLP and HPP of IRI groups were inversely correlated with AST and ALP respectively ( P < 0.01 ),and HPI was closely related to the increase of AST ( r =0.751,P < 0.01 ).Conclusion These results demonstrate CT perfusion is sensitive to detect the hemodynamic changes.Perfusion parameters are closely correlated to the degree of liver injury in the rabbit IRI model.
3.Quantitative study of rabbit hepatic ischemia reperfusion injury with apparent diffusion coefficient values: comparison with pathology and biochemistry
Chengwei GUO ; Changhong LIANG ; Shuixing ZHANG ; Sandi SHEN ; Zaiyi LIU ; Qianjun JIA
Chinese Journal of Radiology 2011;45(9):874-878
Objective To explore the value of DWI ADC in the diagnosis of hepatic ischemia reperfusion injury (IRI) at 3.0 T and investigate the mechanism by comparison with liver enzyme and pathological findings. MethodsForty-two New Zealand white rabbits were divided randomly into ( n = 6,each) six IRI groups by rank sum test. The IRI animals underwent left lobar ischemia for 60 min and were reperfused 0. 5 h, 2. 0 h, 6. 0 h, 12. 0 h, 24. 0 h and 48. 0 h later. One Sham operative group underwent laparotomy without liver ischemia. T2 WI, T1 WI, DWI and contrast-enhanced T, WI were performed with 3.0 T magnetic resonance imaging scanner in each group respectively. For DWI, b-values of 20, 50, 100,200,300,400,500 and 600 s/mm2 were used respectively. Blood samples were taken to detect the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at different time points. Liver samples were examined histologically after MRI scanning. One-way analysis of variance (ANOVA) was used to determine differences, followed by LSD-t test for multiple comparisons. ResultsOverall, ADC decreased markedly at the early IRI phase ( 0. 5 h), drastically increased in the 2.0 h group, and then ascended slightly from 6. 0 h to 48.0 h after reperfusion, except for a transient decrease at the time point of 24. 0 h. When b values were 20, 50, 100,200 and 300 s/mm2, the ADC values in the Sham group were (3.47 ±0.53) × 10-3, (3.11 ±0.39) ×10-3, (2.87 ±0.19) ×10-3, (2.56 ±0.37) × 10-3 and (1.95 ±0.33) ×10-3mm2/s, (2.63±0.31)±10-3, (2.47±0.32) ×10-3, (2.12±0.38) ×10-3, (2.01±0.51) ×10-3and (1.61 ±0.17) ×10-3mm2/s in the 0.5 h group, (2.72 ±0.09) ×10-3, (2.51±0. 11) ×10-3, (2.28 ±0.30) ± 10-3, (1.96 ±0. 14) × 10-3 and (1.58 ±0. 17) × 10-3mm2/s in the 24.0 h group, respectively. ADC of 0. 5 h and 24. 0 h groups were significantly lower than that of Sham group (P<0.05) when b value was under 300 mm2/s.In the Sham, 0.5 h, 2.0 h, 6.0 h, 12.0 h,24.0 h and 48. 0 h IRI groups, they were (80±8), (181 ±34), (413 ±62), (474 ±83), (424 ±41 ),(332 ±41 )and(302 ±39) U/L for the levels of ALT,and (79 ± 10), (454 ±55), (547 ±72), (607±31 ), (649 ±79), (785 ±49) and ( 1526 ± 167) U/L for the AST respectively. The levels of AST and ALT in IRI groups were significantly higher than those in the Sham group ( P < 0. 01 ).Histological findings showed diffuse hepatocytes swelling and erythrocytes depositing in the hepatic sinusoids, portal area, central venous and arterials at the initial phase.With the injury aggravated, inflammatory cell infiltration,hepatocyte nuclear condensation of apoptosis, sinusoidal dissociation and coagulation necrosis developed eventually. Conclusion 3.0 T DWI can monitor the pathological process of rabbit liver ischemia reperfusion injury dynamically, and provides a feasible imaging modality for clinical diagnosis and treatment.