Histone deacetylases (HDACs) constitute a family of enzymes that play important roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation and apoptosis of cancer cells. However, the biological function of HDAC5 in glioma cells has not been fully understood. In the present study, we found that the mRNA and protein levels of HDAC5 are increased in human glioma tissues and cell lines. In addition, overexpression of HDAC5 promoted proliferation of glioma cells, as measured by the MTT assay. By contrast, HDAC5 gene silencing using small interfering RNA (siRNA) inhibited cell proliferation. Furthermore, we demonstrated that HDAC5 enhances Notch 1 expression at both the mRNA and the protein level in glioma cell lines. Taken together, these results demonstrated, for the first time to the best of our knowledge, that HDAC5 promotes glioma cell proliferation, and suggest that this effect involves the upregulation of Notch 1. Therefore, our study may provide a novel therapeutic target for treatment of gliomas.

Epicardial fat, a local visceral fat depot surrounded by visceral pericardial sac, surrounds the coronary arteries for most of their course and may contribute to the development of coronary atherosclerosis by local production of inflammatory cytokines. Some studies on non-invasive measurement of epicardial fat mass have shown that epicardial fat mass is associated with the increased incidence of coronary artery disease (CAD), onset and progression of coronary plaque, mainly including major adverse cardiovascular events, myocardial ischemia, and atrial fibrillation. In the present study the correlation of adiponectin, chemerin, and vascular endothelial growth factor (VEGF) with the epicardial fat volume in patients with coronary artery disease was explored, and the risk factors for vascular remodeling of CAD patients were analyzed.

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ObjectiveThe study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma.MethodsThe expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo.ResultsMAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma.ConclusionMAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

Isolated intracranial myeloid sarcoma (MS) is an unusual variant tumor with few cases reported so far in the medical literature. A 29-year-old woman was admitted to our hospital presenting progressive visual loss in the right eye and weight loss (20 kg) without a previous history of hematological disease (HD). Radiologic evaluation showed the evidence of intracranial mass. Histologically, the resected tumor was composed of a uniform population of primitive cells and primarily misdiagnosed as a T-cell non-Hodgkin's lymphoma (NHL). Chemotherapy with cyclophosphamide, doxorubicin, vinblastine, and prednisone (CHOP) was ineffective. A biopsy and histopathological evaluation were repeated, and immunohistochemical staining revealed the positivity of immature cells to an extensive panel of myeloid markers. These findings were consistent with a diagnosis of MS and bone marrow infiltration. Literature reviews of previous cases were also undertaken.