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Wuhan, China

Li H.,Huazhong University of Science and Technology | Wu K.,Huazhong University of Science and Technology | Tao K.,Huazhong University of Science and Technology | Chen L.,Huazhong University of Science and Technology | And 7 more authors.
Hepatology | Year: 2012

The interaction between T cell immunoglobulin- and mucin-domain-containing molecule (Tim-3) expressed on T helper 1 (Th1) cells, and its ligand, galectin-9, negatively regulates Th1-mediated immune responses. However, it is poorly understood if and how the Tim-3/galectin-9 signaling pathway is involved in immune escape in patients with hepatocellular carcinoma (HCC). Here we studied the expression, function, and regulation of the Tim-3/galectin-9 pathway in patients with hepatitis B virus (HBV)-associated HCC. We detected different levels of galectin-9 expression on antigen-presenting cell (APC) subsets including Kupffer cells (KCs), myeloid dendritic cells (DCs), and plasmacytoid DCs in HCC. The highest galectin-9 expression was on KCs in HCC islets, not in the adjacent tissues. Furthermore, Tim-3 expression was increased on CD4+ and CD8+ T cells in HCC as compared to the adjacent tissues, and Tim-3+ T cells were replicative senescent and expressed surface and genetic markers for senescence. Interestingly, tumor-infiltrating T-cell-derived interferon (IFN)-γ stimulated the expression of galectin-9 on APCs in the HCC microenvironment. Immunofluorescence staining revealed a colocalization of Tim-3+ T cells and galectin-9+ KCs in HCC. Functional studies demonstrated that blockade of the Tim-3/galectin-9 signaling pathway importantly increased the functionality of tumor-infiltrating Tim-3+ T cells as shown by increased T-cell proliferation and effector cytokine production. Finally, we show that the numbers of Tim-3+ tumor-infiltrating cells were negatively associated with patient survival. Conclusion: Our work demonstrates that the Tim-3/galectin-9 signaling pathway mediates T-cell senescence in HBV-associated HCC. The data suggest that this pathway could be an immunotherapeutic target in patients with HBV-associated HCC. © 2012 American Association for the Study of Liver Diseases. Source


Xu Q.,Huazhong University of Science and Technology | Liu C.-Q.,Wuhan Blood Center | Guo E.-S.,Huazhong University of Science and Technology
Chinese Journal of Cancer Prevention and Treatment | Year: 2014

OBJECTIVE: To investigate the effects of Con A combined with lymphocytes on morphology, viability, apoptosis and sensitivity to cisplatin of ovarian cancer cell line SKOV3 in vitro.METHODS: Peripheral blood mononuclear cells (PBMCs) from normal healthy blood donors were prepared by Ficoll-Hypaque gradient centrifugation. Lymphocytes were isolated after monocytes adherent followed by coculture with SKOV3, groups were divided as follows: Control group (SKOV3 without treatment), Experimental group 1 (SKOV3 were treated with 5 μg/mL Con A), Experimental group 2 (coculture of SKOV3 and lymphocytes), Experimental group 3 (coculture of SKOV3 and lymphocytes treated with 5 μg/mL Con A). After 7 days, SKOV3 cells were isolated and continued to be cultured followed by several experiments: Cell morphology was observed by optical microscope; Cell viability was detected using CCK8 at 24 and 48 h; Apoptosis was assessed by flow cytometry at 24 and 48 h; 4) Apoptosis was assessed by flow cytometry after SKOV3 cells were treated with 0 and 60 μmol/L cisplatin for 24 and 48 h.RESULTS: Compared with control group, there was no change in experimental group 1 and 2, but there were significant changes happened in SKOV3 cells: cellular protruding decreased and cells turned round; Compared with control group, cell viability at 24 and 48 h in experimental 1 were (105.68±7.12)% (z=-1.256, P=0.30) and (111.90±8.28)% (z=-1.766, P=0.13), and in experimental 2 were (101.05±5.92)% (z=-0.215, P=0.79) and (109.72±6.54)% (z=-1.766, P=0.13), there was no significant difference; but in experimental 3 the cell viability at 24 and 48 h were (25.08±7.71)% (z=-2.087, P=0.004) and (14.6±4.41)% (z=-3.431, P=0.001), the difference was significant. Compared with control group, cell apoptosis at 24 and 48 h were in experimental 1 were (4.43±1.49)% (z=-2.78, P=0.61) and (10.95±1.09)% (z=-1.982, P=0.08), and in experimental 2 were (4.79±0.83)% (z=-1.349, P=0.28) and (10.59±1.03)% (z=-1.349, P=0.28), there was no significant difference; but in experimental 3 the cell viability at 24 and 48 h were (13.88±1.00)% (z=-2.247, P=0.003) and (21.37±2.35)% (z=-2.137, P=0.006), the difference was significant. Compared with control group, cell apoptosis after treated with cisplatin for 24 and 48 h were in experimental 1 were (11.25±1.86)% (z=-0.361, P=0.59) and (33.66±4.96)% (z=-0.536, P=0.54), and in experimental 2 were (10.32±0.14)% (z=-0.225, P=0.65) and (31.56±6.21)% (z=-0.163, P=0.83), there was no significant difference; but in experimental 3 the cell viability at 24 and 48 h were (41.99±6.66)% (z=-2.14, P=0.03) and (66. 5±2.55)% (z=-1.909, P=0.04), the difference was significant.CONCLUSION: Con A combined with lymphocytes, but not Con A or lymphocytes, can change the morphology of SKOV3, decrease its viability, promote its apoptosis, and increase the sensitivity to cisplatin in vitro. Source


Ning Z.,University of Science and Technology of China | Zhang Y.,University of Science and Technology of China | Chen H.,Wuhan Blood Center | Wu J.,University of Science and Technology of China | And 3 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2014

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of estrogen receptors alpha and beta, is a potential protooncogene implicated in several human cancers, including sexual hormone-responsive or sexual hormone-nonresponsive cancers. However, the functions of PELP1 in colorectal cancer remain unclear. In this study, western blot and bioinformatics revealed that PELP1 expression was higher in several colorectal cancer cell lines than in immortalized normal colorectal epithelium. PELP1 silencing by short hairpin RNA promoted the senescence and inhibited the proliferation, colony formation, migration, invasion, and xenograft tumor formation of the CRC cell line HT-29. Moreover, PELP1 silencing was accompanied by c-Src downregulation. c-Src upregulation partly alleviated the damage in HT-29 malignant behavior induced by PELP1 RNA interference. In conclusion, PELP1 exhibits an oncogenic function in colorectal cancer through c-Src upregulation. © 2014 Zhifeng Ning et al. Source


Tang Y.,Huazhong University of Science and Technology | Liu D.,Huazhong University of Science and Technology | Zhang L.,Wuhan Blood Center | Ingvarsson S.,University of Iceland | Chen H.,Huazhong University of Science and Technology
PLoS ONE | Year: 2011

miRNAs have been found to repress gene expression at posttranscriptional level in cells. Studies have shown that expression of miRNAs is tissue-specific and developmental-stage-specific. The mechanism behind this could be explained by miRNA pathways. In this study, totally 54 miRNAs were analysed in 7 matched human foetal and adult organs (brain, colon, heart, kidney, liver, lung and spleen) using real-time PCR. Quantitative analysis showed that a big proportion of the 54 miRNAs have higher general expression in the organs of the foetal period than the adult period, with the exception of the heart. The miRNA gene promoter methylation level in the adult stages was higher than in the foetal stages. Moreover, there is a high general expression level of several miRNAs in both stages of brain, kidney, liver, lung and spleen, but not seen in colon and heart. Our results indicate that the miRNAs may play a bigger role in the foetal stage than the adult stage of brain, colon, kidney, liver, lung and spleen. The majority of the miRNAs analysed may play an important role in the growth and development of brain, kidney, liver, lung and spleen. However, a minority of the miRNAs may be functional in colon and heart. © 2011 Tang et al. Source


Zhou X.-Y.,Beijing Hospital and Beijing Institute of Geriatrics | Zhou X.-Y.,Quality Control Laboratory | Zhu F.-M.,Zhejiang Blood Center | Li J.-P.,Liaoning Blood Center | And 44 more authors.
PLoS ONE | Year: 2015

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169, 995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169, 995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies. © 2015 Zhou et al. Source

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