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Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.
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Objective To investigate the influence of gemcitabine chemotherapy on levels of regulatory Tcells (Tregs) in peripheral blood for patients with pancreatic cancer and provide evidence and reference for improving the efficacy of adoptive im-munotherapy .Methods 32 patients were enrolled in this study from January 2012 to October 2014 ,among whom 16 received gemcitabine chemotherapy combined with adoptive immunotherapy (gemcitabine group) ,the other 16 patients received adoptive immunotherapy only(control group) .The level of Tregs in peripheral blood ,side effect and overall survival were observed be-fore and after the therapy .Results The number of Tregs in peripheral blood was significantly decreased after gemcitabine chemotherapy ,and it was also lower than that of the control group .The overall survival time of the gemcitabine group was 1.3 mo longer than the control group(10 .0 mo vs 8 .7 mo) .Conclusion Therapeutic regimen of gemcitabine can remarkly de-plete Tregs in peripheral blood of patients with pancreatic cancer ,effectively regulate tumor immune tolerance ,and improve the efficacy of adoptive immunotherapy .
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Objectives To investigate the efficacy and toxicity of bortezomib based combination therapy for Chinese patients with relapsed or refractory multiple myeloma(MM),and to determine the combination regimen,dosage and cycles in application of bortezomib for MM therapy.Methods Forty-six patients with refractory or relapsed myeloma were treated with bortezomib(1.3 mg/m2)as an intravenous bolus twice weekly for 2 weeks on day 1,4,8,and 11 in a 3-4 week cycle,in combination with dexamethasone,dexamethasone plus thalidomide, CD(C-cytoxan,D-dexamethasone),MD(M- mitoxsnteone),DCEP(E-etoposide,P-platinol),and DT-PACE regimens(T-thalidomide,A-adriamycin). Response to bortezomib was evaluated according to the criteria of the International Myeloma Working Group (IMWG)before initiation of each cycle.Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria,version 3.0.Forty-nine matched patients with relapsed and refractory MM who received thalidomide based combination therapy were used as a historical control group.Results Among 43 of the 46 patients whom could be evaluated,the overall response rate was 72.1%(the control group was 51.0%,P＜0.05),including complete response in 5 patients(11.6%),very good partial response in 12 patients(27.9%),and partial response in 14 patients(32.6%).The overall response rate after one and two cycles was 30.2%and 58.1%(P＜0.05),respectively.The frequent adverse events were thromboeytopenia(62.8%),fatigue(55.8%),nausea(51.2%)and peripheral neuropathy (30.2%);all of the events could be tolerated.The most common adverse event in the control group was constipation(69.4%),followed by fatigue(59.2%)and dizziness(46.9%).Conclusions Bortezomib based combination therapy is a new effective therapy in relapsed or refractory myeloma patients with a higher response rate and difierent toxicities as compared with thalidomide based combinations.
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Objective:To induce myeloma specific cytotoxic T cells response in vitro mediated by autologous dendritic cells generating from multiple myeloma(MM) patients.Methods:Monocytes isolated from the peripheral blood of MM patients were cultured in serum free medium with 800 U/ml GM CSF and 600 U/ml IFN? for 8 days to generate DCs.These DCs were pulsed by U 266 cells treated with mitomycin C and their lysates,and then incubated with autologus T lymphocytes for 5～7 days to induce antigen specific CTL.MTT assay was performed to examine the U 266 cell specific lysis.Results:DCs derived from MM patients carried a typical dendritic like morphology,they highly expressed CD86,CD54 and class II MHC molecule(HLA DR) on cell surface.Specific killing of U 266 cells mediated by DCs were tested with MTT assay.At an effector/target ratio of 20/1,specific cytotoxic activities against U 266 cells(28.0%?7.6% and 21.2%?5.4%,respectively),were observed,but without antigen stimulation,the killing rate was 11.7%?4.3%,without DC mediation,the killing rate was 15.6%?4.8% and 13.1%?5.5%(P
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20?10 6/L were observed in the blood. No patients presented bone pain, fever, abnormal function of liver and kidney, and so on. Conclusions:Our results indicated that rhG-CSF is efficacious and safe in auto-PBSCT for patients with plasma cell diseases. Therefore, the expense of hospitalization would be reduced significantly.