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Macrophage migration inhibitory factor (MIF) is a cytokine of pluripotent biological behavior. With the in-depth research of MIF on molecular biology and clinic, it has been found that MIF is closely re-lated to the gastrointestinal tumor' s proliferation and invasion. In this review, we mainly discuss the correla-tion between MIF and gastrointestinal tumor.
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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.
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Colorectal cancer, C RC, is a kind of cancer, which has a high rate of morbidity and mortality.Liver metastasis is the most frequent metastasis way in CRC, and related to the prognosis of the patients.There are many studies on the treatment of colorectal liver metastasis. The resection of the metastasis is one of the major treatments. Other treatments, including chemotherapy, alleviative and immunogenic treatments,are beneficial supplements to the resection. We summariz the indications, contraindications, managements and effects of these treatments.
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Hereditary nonpolyposis colorectal cancer as a eolorectal cancer is of most hereditary characters.With developing of the molecular genetics on detection technology,mismatch repair gene has already been detected by multi-approach,and been applied to screen hereditary nonpolyposis eolorectal cancer patients.In this artical,we mainly discuss the correlated study progression between hereditary nonpolyposis eolorectal cancer and several mismatch repair genes such as MSH2,MLH1,MSH6,PMS1,PMS2,MLH3 and EXO1.
