الملخص
Objective To investigate the effects of ISO-1, a selective MIF tautomerase activity inhibitor, on liver metastasis in a BALB/c mouse model of colonic cancer. Methods Micmporous migration assay was used to determine the effect of ISO-1 on the invasion abilities of CT26 cells. Orthotopic transplantation of fresh colonic tumor fragments into the hernial sac of cecum was used in a BALB/c mouse model of eolorectal cancer. Thirty mouse models were divided into three groups and treated respectively with ISO-1 (0. 2 ml, 20 mg/kg), 5% DMSO and NS ( normal sodium) twice a week, iutraperitoneally. After 4 weeks, mice were sacrificed and the whole livers were made into serial slices to detect the occurrence of liver metastasis. Serum MIF tautomerase activities were measured using L-dopachrome methyl ester, ELISA was used to test serum VEGF concentrations. Immunohistochemical staining of CD31 was used for comparing microvascular density (MVD) of tumor tissues. Results 100 μmol/L ISO-1 treatment for 24 hours significantly reduced the average number of the cells penetrating polycarbonates, ( 151 ± 19 ) vs. ( 178 ± 9 ), P<0. 01. Serum MIF tautomerase activities were significantly inhibited after ISO-1 treatment (51% vs. 81%, P <0. 01 ). Compared with DMSO and NS treatment, ISO-1 decreased the occurrence of liver metastasis ( 10% ,60% and 70% ,respectively;x2 = 8. 30, P < 0. 05 ). Also ISO-1 decreased serum VEGF levels ( 15 ± 7 ) pg/ml, ( 63 ± 11 ) pg/ml and ( 67 ± 8 ) pg/ml, respectively; P < 0. 01 and the MVD of tumor tissues (17±4) ,(36±7) and( 38±5) ,respectively; P<0. 01. Conclusion In vitro ISO-1 inhibits the invasion ability of CT26 cells. In vivo ISO-1 reduces the occurrence of liver metastasis, possibly by a mechanism of inhibiting MIF tautomerase activities, down-regulating the expression of VEGF and reducing MVD.
الملخص
Objective The therapeutic effect for hemorrhage from esophageal varices(EV)with conservation,surgical intervention,EVL(esophageal variceal ligation)or TIPSS(transvenous intrahepatic portal systemic shunt)were compared.Methods The clinical materials of 72 patients with bleeding from EV were retrospectively reviewed. Results With octreotide(n=23) the rates of hemostasis within 48 hours and hospital mortality maintained 78.3 and 8.7 percent respectively.Rebleeding occurred within 7 days in 3/18 cases(16.7％ ) and within 150 days in 6/18 cases(33.3％ ),resulting in death in 4/18 instances;with emergency surgery death encountered in 4 out of 13 cases(30.8％ ),while with elective operation no death could be traced,7.7 percent of the series with octreotide rebled within 1 year and 19.2 percent did so after 2 years;after EVL(n=8) the varices reduced obviously or eliminated in 75 percent without rebleeding and death in follow-up period of 1～ 33 months;EV disappeared or ameliorated immediately following TIPSS in 9 out of 10 successful cases,yet the rebleeding rate attained 30 and 80 percent within 1 and 5 years respectively.The stent was proved afterwards stenosed or obstructed by ultrasonography.Encephalopathy ensued in 40 percent of the cases with 6 deaths in 61 months. Conclusion It was assumed that octreotide exerted affimative effect in the control of acute bleeding,particularly indicated for patients who were too weak to have endoscopy in 24 hours after admission,however bleeding often recurred following the use;elective surgery might reduce the early rebleeding rate and prolong the interval of rebleeding;EVL was capable of eradicating EV with simplicity;TIPSS had poor long-term effect.