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Objective To determine the relative and independent risk factors of survival in patients with non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC).Methods The clinical records of 109 patients who underwent surgical resection for NBNC-HCC at Tianjin Medical University Cancer Institute & Hospital between January 2010 and January 2013 were retrospectively analyzed.The risk factors influencing disease-free survival (DFS) and overall survival (OS) were used as primary outcome measures.Univariate analysis was conducted to determine the relative risk factor predicting prognosis of NBNC-HCC,and the Cox proportional hazards model was used to determine independent risk factors of DFS and OS.Results For the 109 NBNC-HCC patients,the 1-,2-,3-year overall survival rates were 90.8％,78.0％ and 65.1％,respectively.The compounding disease-free survival rates were 74.0％,63.3％ and 55.8％,respectively.Univariate analysis showed the AFP level,ascites,and TNM staging were the risk factors of OS (all P ＜ O.05).The AFP level,ascites,BCLC stage,TNM staging were related with DFS (all P ＜ 0.05).Multivariate analysis demonstrated AFP and ascites to be the independent risk factors of OS and DFS.Conclusions AFP and ascites were independent risk factors of OS and DFS.For the NBNC-HCC patients,a strong positive AFP with ascites indicated poor prognosis.
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To generate an epitope-mutated foot-and-mouth disease virus (FMDV) as a marker vaccine, the infectious clone pAsia 1-FMDV containing the complete genomic cDNA of Asia 1 type FMDV was used as backbone, the residues at positions 27 and 31 in the 3D gene were mutated (H27Y and N31R). The resulting plasmid pAsia 1-FMDV-3DM encoding a mutated epitope was transfected into BHK-21 cells and the recombinant virus rAsia 1-3DM was rescued. The recombinant virus showed similar biological characteristics comparable with the parental virus. In serological neutralization test the antisera against recombine virus have a good reactivity with parental virus. The antisera against the mutant virus were shown to be reactive with the mutated epitope but not the wild-type one. The results indicated that the two virus strains could be distinguished by western blotting using synthetic peptides. This epitope-mutated FMDV strain will be evaluated as a potential marker vaccine against FMDV infections.
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Animals , Cell Line , DNA, Complementary , Epitopes , Genetics , Foot-and-Mouth Disease Virus , Genetics , Immune Sera , Neutralization Tests , TransfectionABSTRACT
Objective To observe the effects of Astragalus polysaccharide ( APS) on tumor growth, cytokine and immune function impairment induced by cisplatin ( DDP) in mice bearing Lewis lung cancer.Methods A total of 90 mice were used in this study:10 for blank control group, and 80 mice with transplanted Lewis lung cancer were randomly divided into 8 groups:model control group (physiological saline), positive control group treated with DDP (6 mg/kg), low dose APS (50 mg/kg), moderate dose APS (100 mg/kg) and high dose APS (200 mg/kg) groups and three combinations of APS+DDP groups ( the same three APS levels with half dose of DDP, respectively) .0.3 mL of the drugs was intraper-itoneally injected to the mice, respectively, on the second day after moldeling.DDP was injected once a week and other drugs were injected once per day for consecutive 20 days.On the 21st day, blood samples were collected and serum levels of cytokine IL-2, IL-6, IL-12 and TNF-αwere determined by ELISA, and the tumor inhibition rate and immune organ in-dexes were assessed.Results The tumor inhibition rates of the positive control, low, moderate and high dose APS groups and three combinations of APS+DDP groups of mice bearing Lewis lung carcinoma were 49.30%, 17.21%, 39.68%, 17.21%, 51.02%, 57.21%and 65.11%, respectively.Compared with the model group, P<0.05 or P<0.01, and compared the three combination groups with the DDP group, P<0.05.Compared with the blank control group, the spleen index was significantly increased in the moderate and high dose APS groups and the three combinations of APS +DDP groups.There was a significant difference between the spleen indexes of the model control group, and the spleen indexes of high dose APS and the combination with high dose APS groups were significantly higher than that of the model control group (P<0.05).Compared with the DDP group, APS in various doses and combinations increased the thymus index and spleen index.Conclusions APS can improve the levels of cytokine IL -2, IL-6, IL-12 and TNF-αin mice bearing Lewis lung cancer, enhance the immune function impairment induced by DDP, has certain protective effect on the immune organs, and inhibit the growth of Lewis lung cancer in mice.When APS is used in combination with a half-dose of DDP, APS enhanced the inhibition of tumor growth.This mechanism may be related to the enhanced body immune function.Our results indicate that APS enhances the therapeutic effect of DDP and reduces its toxicity, therefore, may have potential application value in future treatment of solid tumors.
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With the progess in studying gene structure and function of foot and mouth disease virus (FMDV), FMDV can express exogenous genes in different sites. Through transforming and modifying FMDV can achieve different application purposes such as improving virus titer, introducing tag, improving immune responses, and reducing pathogenicity. From the perspective of FMDV receiving inserted exogenous gene, this paper mainly describes the latest relevant developments of FMDV's expression to exogenous gene.
Subject(s)
Foot-and-Mouth Disease Virus , Genetics , Genetic Engineering , Mutagenesis, InsertionalABSTRACT
Objective To investigate the effects of high concentrations of iodide exposure on mitochondrial superoxide production,cell viability and cell damage in the thyroid of metallothionein Ⅰ/Ⅱ knockout (MT-Ⅰ/Ⅱ KO) mice and corresponding wild type (WT) mice.Methods Thyroid cell suspension of six to eight weeks old healthy male MT-Ⅰ/Ⅱ KO mice and WT mice were prepared.The thyroid cells were treated with high concentrations (10-4,10-3,10-2 mol/L) of potassium iodide(KI),or 10-3 mol/L hydrogen peroxide(H2O2) for 2 hours,respectively.Cell viability was evaluated with methyl thiazolyl tetrazolium(MTT) assay.Lactate dehydrogenase (LDH) level in cell culture medium was detected by enzyme-linked immunosorbent assay(ELISA).Mitochondrial superoxide production in the thyroid cells was measured by flow cytometry using a fluorescent probe,mitochondrial superoxide(MitoSOX).Results Compared to the control group[(100.00 ± 0.00)％,(100.00 ± 0.00)％],the cell viability of 10-4,10-3,10-2 mol/L KI and 10-3 mol/L H2O2 exposure groups were significantly decreased in the thyroid cells of both WT [(73.63 ± 2.05)％,(72.41 ± 2.26)％,(69.63 ± 2.29)％,(44.90 ± 2.93)％] and MT-Ⅰ/Ⅱ KO mice[(65.40 ± 2.39)％,(64.51 ± 2.27)％,(61.48 ± 2.33)％,(40.80 ± 2.76)％,all P＜ 0.05].Compared to the control group [(1 995.28 ± 30.52),(2 004.96 ± 19.71)U/L],significantly increased LDH activities were detected in the thyroid cells of WT [(2 809.22 ± 156.53),(2 850.80 ± 137.83),(2 920.45 ± 152.92),(4 487.49 ± 130.67)U/L] and MT-Ⅰ / Ⅱ KO mice [(3 261.06 ± 120.44),(3 474.19 ± 142.15),(3 597.08 ± 150.86),(4 706.64 ± 148.57)U/L,all P ＜ 0.05].Compared to the control group (26.49 ± 7.66,37.11 ± 8.48),the MitoSOX red fluorescence intensities of 10-2 mol/L KI and 10-3 mol/L H2O2 groups were significantly increased in WT mice(58.96 ± 5.11,87.95 ± 4.25) and MT-Ⅰ/ⅡKO mice(71.21 ± 5.55,99.76 ± 4.42) by flow cytometry (all P ＜ 0.05).Compared to the thyroid cells in WT mice,significantly decreased cell viability (all P ＜ 0.05),significantly increased LDH activity(all P ＜ 0.05) and significantly increased MitoSOX red fluorescence intensity by flow cytometry (all P ＜ 0.05) were detected in the thyroid cells of MT-Ⅰ/Ⅱ KO mice following treatment with KI or H2O2.Conclusions High concentrations of iodide (10-2 mol/L) and 10-3 mol/L H2O2 may lead to significant increase of mitochondrial superoxide production and LDH activity,decrease of cell viability in both WT and MT-Ⅰ / Ⅱ KO mice.More significant increase of superoxide production is detected in MT-Ⅰ / Ⅱ KO mice,indicating the potential protective role of metallothionein in the thyroid cells of WT mice.