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In the majority of acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein-retinoic acid receptor α (PML-RARα) fusion gene. Studies have reported that neutrophil elastase (NE) cleaves bcr-1-derived PML-RAα in early myeloid cells, leaving only the nuclear localization signal (NLS) of PML attached to RARα. NLS-RARα promotes cell growth and inhibits differentiation in response to ATRA. However, the mechanisms by which NLS-RARα affects cell biological characteristics are yet to be fully elucidated. The present study found that the location of RARαwas altered after it was cleaved by NE. Firstly, NE was overexpressed during the preparation of recombinant plasmid NB-4/pCMV6-NE-Myc to cleave PML-RARα. The total protein expression levels of myc and NE and expression levels of NLS-RARα in nucleoprotein were detected by western blotting. Location of NLS-RARα protein was detected by immunofluorescence and confocal laser scanning. Secondly, a nude mice model was constructed and NE protein, NLS-RARα and RARα protein assays, and the location of NLS-RARα and RARα proteins were assessed as described. The present results showed that, compared with the control groups, the location of NLS-RARα protein was predominantly detected in the nucleus, whereas RARα was mainly distributed in the cytoplasm. These findings were consistent with those of the nude mice model, and these may be used as a foundation to explain the occurrence mechanism of APL. [ABSTRACT FROM AUTHOR]

A component purified from Strongylocentrotus nudus eggs on a diethylaminoethyl cellulose-52 chromatography column and eluted using a NaCl solution gradient (SEP-S), is a homogeneous polysaccharide of α-D-glucan with a reduced molecular weight of 9.33x105 Da, compared with that of S. nudus egg polysaccharide (SEP). In an in vivo antitumor assay of histocompatibility-22 hepatocellular carcinoma in tumor-bearing mice, the inhibitory rates at SEP-S doses of 5, 10 and 20 mg/kg/day were 38.8, 50.7 and 70.3%, respectively. In addition, the spleen and thymus indices and the percentages of cluster of differentiation (CD) 4+ and CD8+ T cells were significantly increased, and the activity of cytotoxic T lymphocytes was notably enhanced, suggesting that the anti-hepatocellular carcinoma activity is mediated by boosting the immune system. In vitro experiments also demonstrated that splenocyte proliferation induced by SEP-S was inhibited by the toll-like receptor (TLR) 2 and TLR4 monoclonal antibodies. These data indicate that SEP-S is a polysaccharide component possessing high anti-hepatocellular carcinoma activity and may be a potential immunotherapy candidate for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]