Time filter

Source Type

Hangzhou, China

Xu L.,Wenzhou University | Huang Y.,Wenzhou University | Tan L.,Wenzhou University | Yu W.,Wenzhou University | And 6 more authors.
International Immunopharmacology | Year: 2015

T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56 + cells (P < 0.05) and CD3-CD56dim cells (P < 0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56 + NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P < 0.05) or with tumor stage T3-T4 (P < 0.05). Tim-3 expression in CD56dim NK-cell subset was higher in patients with tumor size ≥ 3 cm (P < 0.05), or LNM (P < 0.05) or with tumor stage T3-T4 (P < 0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56 + NK cells and CD56dim NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P = 0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-γ production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy. © 2015 Elsevier B.V. All rights reserved.

Xiong Y.,Jilin University | Xiong Y.,Beihua University | Tan Y.,Jilin University | Tan Y.,Cancer Biotherapy Center | Song Y.G.,Beihua University
Hepatitis Monthly | Year: 2014

Background: The hepatitis B virus (HBV) antigen-induced cellular immune response plays an important role in HBV clearance. Changes in the diversity of complementarity determining region 3 (CDR3) and T-cell receptor (TCR) sequences are used to monitor the response of T cells to antigens. Objectives: The aim of the present study was to determine whether the TCR Vβ repertoire of patients with chronic severe hepatitis B (CSHB) undergoes increased stimulation, and to identify conserved motifs in specific TCR Vβ families. Patients and Methods: Peripheral blood mononuclear cells (PBMCs) from 18 patients with CSHB were sorted into CD4+ and CD8+ T subsets, using monoclonal antibody-coated magnetic beads. The TCR Vβ CDR3 was subsequently characterized using immune spectratyping. The TCR Vβ families exhibiting a CDR3 spectratype that underwent monoclonal expansion were sequenced. Results: The number of oligoclonal or monoclonal expansion TCR Vβ families detected in the analyzed CD8+ T cells was significantly higher than the number detected in CD4+ T cells. The CDR3 spectratype analysis showed predominant usage of TCR Vβ5, Vβ7, Vβ9, Vβ12, and Vβ18 families in CD8+ T cell subsets of CSHB patients. Furthermore, conserved amino acid motifs were found to be associated with the monoclonal expansion of CD8+ TCR Vβ families. In addition, JB1S1 and JB2S7 region genes were present at a high frequency. Conclusions: The CD4+ and CD8+ TCR Vβ gene families undergo clonal expansion in CSHB patients, and CD8+ T cells play a major role in the pathogenesis of CSHB. Moreover, the conserved motifs and limited use of joining region genes observed in the CSHB patients of this cohort indicated that similar antigenic epitopes are recognized. © 2014, Kowsar Corp.

Li Y.,Jilin University | Ma C.,Jilin University | Shi X.,Jilin University | Wen Z.,Jilin University | And 3 more authors.
Oncology Reports | Year: 2014

Multiple drug resistance (MDR) is considered a major challenge in the clinical treatment of non-small cell lung cancer (NSCLC). Both nitric oxide synthase (iNOS) and Wnt signaling pathway participate in the regulation of drug resistance, but the interaction between them remains unclear. In the present study, we detected the activation of Wnt/β-catenin signaling in iNOS-induced drug-resistant lung cancer cells, and compared the effect of canonical and noncanonical Wnt pathway on the level of iNOS. Moreover, we investigated the expression of Wnt/β-catenin signaling downstream factors and its main inhibitors. The results indicated iNOS-induced drug resistance was possibly mediated by glutathione S-transferase-π (GST-π) and topoisomerase IIα (TOPO IIα), but not P-glycoprotein (P-gp), and this process was closely associated with the activation of canonical Wnt/β-catenin signaling, but less with noncanonical pathways. The mechanism of iNOS promoting Wnt/β-catenin pathway was mainly dependent on the inverse regulation of Dickkopf-1 (DKK-1) and secreted frizzled-related protein-1 (SFRP-1). Clarifying the relationship between iNOS and Wnt signaling may provide insight into a better understanding of the mechanism of drug resistance development in NSCLC.

Xu L.,Cell and Molecular Biology Laboratory | Chen D.,Cell and Molecular Biology Laboratory | Lu C.,Cell and Molecular Biology Laboratory | Liu X.,Cell and Molecular Biology Laboratory | And 2 more authors.
Annals of Clinical and Laboratory Science | Year: 2015

It is known that dysregulation of the immune system is closely related to the development of lung cancer and that CD8+T lymphocytes play a critical role in antitumor immunity. We analyzed the percentage of CD3+CD8+ T cells in peripheral blood, and expressions of the activated molecules, perforin, CD95, CD28, HLA-DR and CD38 in circulating CD3+CD8+ T cells from 68 lung cancer cases with stage I~II and 61 lung cancer cases with stage III~IV by flow cytometry. 61 lung cancer cases with stage III~IV were followed up for more than 6 months and survival time was recorded. The percentages of perforin+ cells, CD95+ cells and CD38+ cells in fresh CD3+CD8+ T lymphocytes of stage III~IV group were lower than those of stage I~II group (p=0.021; p=0.043; p=0.036). And an increased percentage of CD3+CD8+perforin+ cells was shown to have a positive effect on the survival time in stage III~IV lung cancer patients (p=0.043). Advanced lung cancer patients have characteristics of impairment in the cytotoxicity of circulating CD3+CD8+ T lymphocytes and perforin expression in circulating CD3+CD8+ T cells might be used as a prognostic biomarker for the advanced lung cancer.

Liu Y.,Jilin University | Kang D.,Southern Medical University | Li C.,Jilin University | Xu G.,Jilin University | And 2 more authors.
Molecular Medicine Reports | Year: 2014

As a genetic disease, neurofibromatosis type 1 (NF1) is characterized by abnormalities in multiple tissues derived from the neural crest, including neoplasms in the ends of the limbs. The exact mechanism of nerve growth in NF1 is unclear. In the present study, the gene expression profile of nerves in healthy controls and NF1 patients with macrodactylia of the fingers or toes were analyzed in order to identify possible genes associated with nerve growth. The Whole Human Genome Microarray was selected to screen for different gene expression profiles, and the result was analyzed with Feature Extraction software. The target genes were verified at the transcriptional and translational levels by reverse transcription - polymerase chain reaction and western blotting, respectively. A common set of 28 genes were identified to be changed >5-fold in the NF1 patients compared with the healthy controls. Among them, the metastasis-associated genes, lymphocyte function-associated antigen 1, C-X-C chemokine receptor type 4 and intracellular adhesion molecule 1, and the inflammatory cytokines, interleukin (IL) 1β, IL-6 and IL-8, were down regulated significantly. Mainly genes that changed >10-fold were analyzed in this study, and HOXC8 demonstrated activity in promoting nerve growth. Through the analysis of the mRNA expression of the nerves in the NF1 patients, target molecules contributing to nerve growth during NF1 development were investigated, which aided in improving our understanding of this disease, and may provide a novel direction for nerve repair and regeneration.

Discover hidden collaborations