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Objective:To investigate the expression of coxsackievirus-adenovirus receptor (CAR) in thymic carcinoma and the relationship between CAR and the antitumor activity of oncolytic adenovirus H101.Methods:The expression of CAR in thymic carcinoma tissues and cells were detected by RT-qPCR and Western blot. H101 expression and virus titers in Bcap-37, MP59 and T1889 cells after infection were detected by RT-qPCR and 50% tissue culture infectious dose (TCID 50). The proliferation activity and apoptosis rates of T1889 cells infected with H101 at different multiplicity of infection (MOI) were detected by CCK-8 and flow cytometry. CAR expression in T1889 cells treated with different concentrations of trichostatin A (TSA), a histone deacetylase inhibitor, was detected. H101 expression and virus titers in the TSA-treated and H101-infected cells were detected. Cell activity was detected by CCK-8. The phosphorylation levels of MARK and ERK1/2 and the expression of CAR at protein level in TSA-treated or TSA+ TBHQ (ERK activator) treated cells were detected. Results:CAR expression at both mRNA and protein levels were significantly lower in thymic carcinoma tissues than in adjacent normal tissues ( P<0.01), and lower in MP59 and T1889 cells than in thymic epithelial cells (TEC) and Bcap-37 cells ( P<0.01). H101 expression in MP59 and T1889 cells and the titers of H101 in culture supernatants were significantly lower than those in Bcap-37 cells ( P<0.01). Compared with Bcap-37 cell, the activity of MP59 and T1889 cells was significantly increased and the apoptosis rates were significantly decreased 48 h after H101 infection ( P<0.01). The expression of CAR at both mRNA and protein levels in T1889 cells treated with different concentrations of TSA increased in a dose-dependent manner. When T1889 cells were treated with 0.25 μmol/L of TSA, the expression of H101 at mRNA level and H101 titers were significantly increased ( P<0.05); the phosphorylation levels of MAPK and ERK1/2 proteins were continuously decreased; the expression of CAR was continuously increased. Compared with the TSA treatment group, the expression of CAR at protein level in the TSA+ TBHQ treatment group decreased significantly ( P<0.01), and the p-ERK1/2/ERK1/2 ratio increased significantly ( P<0.01). Conclusions:TSA could up-regulate CAR expression in thymic carcinoma by inhibiting the MARK/ERK1/2 pathway, thereby enhancing the antitumor activity of H101.
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Objective To investigate the expression and clinical significance of tumor necrosis factor recep-tor associated factor 6(TRAF6)in human esophageal cancer.Methods The clinical data of 72 patients with esopha-geal cancer were collected.Immunohistochemistry method was used to determine TRAF6 expression in esophageal carcinoma and its adjacent normal tissue,and its relationship with clinical pathological features was explored.Results The TRAF6 positive expression rate in esophageal cancer tissue was 66.13%,which was significantly higher than that of normal tissue (13.89%),the difference between the two groups was statistically significant(χ2 =56.850,P <0.01).And TRAF6 expression level was significantly correlated with esophageal cancer clinical staging,lymph node metastasis(χ2 =6.818,4.428,all P <0.05),but TRAF6 expression was not correlated with age,sex,tumor differenti-ation.Conclusion The expression level of TRAF6 in esophageal carcinoma was significantly increased,and there was a significant correlation between the TRAF6 expression level and clinical pathological characteristics.
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BACKGROUND:Mesenchymalstem cels have pluripotent differentiation, and can promote cel engraftment and immune regulation. Therefore,we attempt to use human umbilical cord mesenchymal stem cels as anew source for treatment of lung cancer by exploringcelisolation, identification and transplantation combined with chemotherapyforlung cancer in mice. OBJECTIVE:To investigate the isolation and identification of human umbilical cord mesenchymal stem cels and its transplantation combined with chemotherapy for lung cancer inmice. METHODS:Human umbilical cord mesenchymal stem cels were isolated from fresh umbilical cord of newborns and identified using tissue culture and enzyme digestion. Twenty Balb/C nude mouse models of lung cancer were randomly divided into two groups:mice in chemotherapy group were given chemotherapy, and those incombinedgroup given combination of chemotherapy with human umbilical cord mesenchymal stem cel transplantation. RESULTS AND CONCLUSION:Compared with the chemotherapy group, the gastrointestinal tract was rosy and shiny, intestinal mucosa was smooth and complete, and tumor mass and blood indexes significantly decreased in thecombinedgroup (P< 0.05). To conclude, mature human umbilical cord mesenchymal stem cels can be obtained by tissueculture and enzyme digestion, andthecel transplantation combinedwith chemotherapy can significantly reduce gastrointestinal tract damage and themake peripheral hemogram in a stable level.
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BACKGROUND:So far the positive or negative effects of mesenchymal stem cel s on tumor growth and metastasis are under discussion. OBJECTIVE:To explore the mechanism of bone marrow mesenchymal cel s in promoting lung cancer metastasis. METHODS:Primary rat bone marrow mesenchymal stem cel s were obtained by direct adherence method of the whole bone marrow, and differential adherence combined with digestion control method was performed to purify cel s. Lung cancer cel lines were cultured, and the effects of bone marrow mesenchymal stem cel s on the migration, invasion and metastasis of lung cancer cel s were observed by scratch test, cel invasion and migration assays. Orthotopic lung cancer models were established in rats and bone marrow mesenchymal stem cel s were seeded onto the left lung of rats. Then, pathological changes of lung tissues were observed at 14 days after transplannation. RESULTS AND CONCLUSION:After the scratch test, the migration rate of lung cancer cel s became higher, and the scratches healed with time. And after cel transplantation, the number of migrated lung cancer cel s increased, as wel as the ability of lung cancer cel s penetrating the Matrigel was strengthened. Besides, fibrous connective tissues could be found around the lung cancer tissues, and necrosis with distinct boundary and large tumor nuclei;the metastatic tissues showed obvious infiltration and necrosis with large tumor nuclei. These results suggest that bone marrow mesenchymal stem cel s can promote the invasion, migration and metastasis of lung cancer cel lines.