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Objective:To evaluate a Meta-analysis of randomized controlled trials ( RCTs) in multiple sclerosis ( MS) patients to evaluate the efficacy of vitamin D as add-on therapy. Methods: Searched Pubmed,EMbase,the Cochrane Library,CNKI,Wanfang Data base and so on up to february 2016 using the keywords:multiple sclerosis or MS and the drug names:vitamin D orCholecalciferol. Two authors independently selected the articles and extracted the data. We performed meta-analysis using Review Manager ( RevMan) version 5. 3 software. Results:Four RCTs with a total of 247 patients were selected.①Compared to the placebo, the EDSS score[MD=-0. 33,95% Confidence interval (CI)= (0. 68,0. 01),P=0. 05],the annual relapse rate[MD=-0. 08, 95%CI=(-0.37,0.21),P=0.60]and the number of gadolinium-enhancing lesions[MD=-0.16,95%CI=(-0.57,0.25),P=0. 45] showed no significant difference at 12 months,meanwhile the EDSS score[MD=-0. 48,95%CI=(0. 87,-0. 09),P=0. 02] and the annual relapse rate[MD=-0. 27,95%CI=(-0. 52,-0. 02),P=0. 03] were significantly less in the vitamin D group at 24 months.②Safety evaluation:There was no hypercalcaemia in vitamin D treated patients in each studies,main adverse events reported were diarrhoea, fever, constipation, dyspepsia, headache and so on. These symptoms were mild, after stopping drug can relieve the general. Conclusion: Vitamin D as an added in the treatment of MS showed as same as the placebo in some clinical indicators. However,after a longer treatment, the clinical indicators were significantly lower in the vitamin D group. Due to limited quantity and quality of the included studies,further larger and more prolonged studies are merited to verify the above conclusion.
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Objective To investigate the regulation on cell cycle related factor such as Cyclins and P21waf/cip1 by inhibiting histone deacetylase(HDAC)with valproic acid sodium(VPA).Methods HepG2 hep-tocellular carcinoma cells.BGC-823 gastric carcinoma cells and MCF-7 breast cancer cells were cultured with O.75-4.00 mmoL/L VPA for 48 h in vivo.and the cell cycle was analyzed by flow cytometry with PI assay.The protein and mRNA expression of Cyclin A,Cyclin D1,Cyclin E and P21waf/cip1 were analyzed by indirect immu-nofluorescence technique and RT-PCR.respectively.Results Compared with control groups,VPA at concen-trations 0.75-4.00 mmol/L exerted a significant inhibiting effect on G1 phase of HepG2,BGC-823 and MCF-7 cells(P<0.001).and the effect was dose dependent.Cyclin A was down-regulated both at mRNA and protein level in HepG2 and BGC-823 cells(P<0.001),but no difference in MCF-7 cells(P>0.05).Cyclin D1 was down-regulated both at mRNA and protein level(P<0.001)and P2lwaf/cip1 was up-regulated both at the mRNA and protein level in the three cell lines(P<0.001);Conversely,protein and mRNA expression of Cyclin E were unchanged upon treatment with VPA(P>0.05).Condusion Acetylization of histone intervened with VPA can regulate Cyclin D1 and P21waf/cip1 expressions obviously.To the expression of Cyclin A,it shows some difference according to the histogenesis and phenotypes of different carcinoma types.But there is not any obvious function on Cyclin E.Down-regulating Cychn D1 and up-regulating P21waf/cip1 may be the common target path-way in the inhibition of cell cycle G1 phase exerted by VPA.
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Objective To investigate the effect and the mechanism of up-regulating histone acetylizad level with a selective inhibitor of HDACs-Valproate acid sodium (VPA) on breast cancer cell proliferation. Methods MCF-7 cells were cultured with 0.75-4.0 mmol/L valproic acid (VPA) for 24, 48, 72, 96 hours in vitro, the inhibiting rate was tested by MTT assay. Cell cycle was analyzed by flow eytome- try with PI assay, and the protein and mRNA expressions of Cyelin A, Cyclin DI, Cyclin E, P21Waf/cipl of MCF-7 cells after 1.5, 3.0 mmol/ L VPA treated were analyzed by indirect immunofluorescence technique and RT-PCR respectively. Results After cultured with 0.75 -4.0 mmol/L valproic acid (VPA) for 24, 48, 72, 96 hours, the inhibiting rate of experimental groups increased significantly(P<0.01) and a dose and acting time dependent manner was found. As to cell cycle, the percentages of GI, S, M phrase in control groups remained the same. Contrary to control groups, 0. 75 -4.0 mmo]/L VPA induced a significant arrest in G1 phrase ( P<0.01), and a total of 55.4% -82.8% G1 phrase ratio were found. P21Waf/cipl was up-regulated both at the mRNA and protein level while Cyclin D1 was down-regulated ( P<0.001). Conversely, neither mRNA nor protein expression of Cyclin A, Cyclin E showed difference ( P>0.05). Conclusions Up- regulating histone acetylizad level can inhibit breast cancer cell proliferation, induce cell cycle arrest in G1 phrase. VPA, as a I class of histone deaeetylase inhibitor, can be used as an option in the treatment of breast cancer. The mechanism may include up-regulating P21Waf/cipl mRNA and protein expression and down-regulating Cyclin D1 mRNA and protein expression.
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Objective: To investigate antisense integrin?V and ?3 gene therapy in Rats mod- el of Pancreatic Carcinoma. Methods: The antisense integrin?V and ?3 expression plasmids wereelectrobloted into pancreatic tumours of rats induced by dimethylbenzanthracine,The tumor inhibit rate was calculated, the tumor microvessel density(MVD)with the immunohistochemical staining and tumor apoptosis with TUNEL were examined. Results: The tumor weight of the control group, ?V group, ?3 group an- d?V?3 group was (1.167?0.79)g(,0.953?0.26)g(,1.013?0.42)g(,0.788?0.56)g respectively. The dif- ference was significant among them(P
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Objective:To investigate modulation of a specific HDAC inhibitor,Valproate acid sodium(VPA),on expression of Caspase3,Caspase8,Caspase9 by inhiting HDAC,as well as apoptosis rate of cancer cells treated with VPA and the specific inhibitors of Caspase3,Caspase8,Caspase9.Methods:Heptocellular carcinoma cells-HepG2,gastric carcinoma cells-BGC-823 and breast cancer cells-MCF-7 were cultured with 0.75-4.0 mmol/L of VPA for 48 hrs in vivo,apoptosis was analyzed by flow cytometry with Annexin V/PI assay.The activities and protein expressions of Caspase3,Caspase8,Caspase9 were detected by spectrophotometry and indirect immunofluorescence technique.Results:Contrary to control groups,VPA at concentrations between 0.75 and 4.0 mmol/L induced a significant apoptosis in HepG2,BGC-823,MCF-7 cells(P0.05).The apoptosis rates of cancer cells treated with VPA and specific inhibitors of Caspase3,Caspase9 together was lower than in the groups with VPA treatment singlely(P