Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Effect of PDTC on the NF-κB activation and the expression of inflammatory cytokines in THP-1 macrophages induced by rPVL / 中华微生物学和免疫学杂志

Objective To investigate effect of PDTC on the NF-κB activation and the expression of inflammatory cytokines in THP-1 macrophages induced by rPVL.Methods The study was divided into three groups:PBS-treated control group,rPVL-treated group and PDTC group which was given 100 μmol/L PDTC at 60 min before rPVL exposure.Immunohistochemistry method was used to test the translocation of NF-κB protein; the expression of NF-κB and IκB protein was analyzed by Western blot; RT-PCR and ELISA was performed to test expression of IL-8 and L-6 in THP-1 macrophages.Results Compared with rPVL-treated group,the activation of NF-κB and the expression of IL-8 and L-6 in PDTC group was significantly decreased.The protein secretions of IL-8 and IL-6 were reduced to 6.78 ng/ml,3.88 ng/ml,receptively(P ＜0.05).Conclusion The inhibitor of NF-κB,PDTC,could significantly decrease the secretion of pro-inflammatory in THP-1 macrophages by rPVL,and it suggested that PDTC played an important role in protecting tissues from damage induced by rPVL.

Construction and expression of a prokaryotic vector of recombinant human adiponectin global domain / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct and express the recombinant human adiponectin (gAd) global domain.</p><p><b>METHODS</b>gAd complementary DNA (cDNA) was obtained from human fat tissue by RT-PCR. The PCR product was cloned into the vector pMD18-T and the prokaryotic expression vector pET32a(+). The recombinant vector was identified by digestion with double restriction endonucleases SalI and EcoRI, PCR and sequence analysis. The recombinant plasmid containing gAd gene was transformed into E. coli BL21 (DE3), and the expression of the fusion protein His-gAd was induced by IPTG.</p><p><b>RESULTS</b>The gAd cDNA of 412 bp was obtained from the total RNA of the fat tissue and verified by sequence analysis.</p><p><b>CONCLUSION</b>The recombinant plasmid could stably express the 34-kD fusion protein His-gAd in the engineered bacteria in the form of inclusion bodies.</p>

The relationship between oxidative stress and endothelium-dependent vasodilatation in obese subjects / 中国糖尿病杂志

Objective To evaluate the relationship of the levels of serum oxide and antioxide with endothelium-dependent vasodilatation(EDV) in obese subjects and to explore the effect of oxidative stress on endothelial dysfunction in obese subjects. Methods 20 euglycemic obese males (Ob) and 13 age- matched normal controls (NC) underwent euglycemic hyperinsulinemia clamp study to evaluate the peripheral glucose disposal rate (GDR) in steady-state and brachial artery ultrasound studies to assess the endothelium-dependent vasodilatation (EDV). The serum levels of ROS, MDA, GSH-PX, GSH and free fatty acids (FFAs) were measured. Results The serum ROS, MDA and FFA concentrations were significantly higher in Ob group than in the controls (P