Programmed cell death ligands (PD-Ls) are expressed in tumor cells where they bind to programmed cell death-1, an immunocyte co-receptor, resulting in tumor cell evasion from the immune system. Chemotherapeutic drugs have been recently reported to induce the expression of PD-L, such as PD-L1, in some cancer cells. However, little is known regarding PD-L2 expression and its role in oral squamous cell carcinoma (OSCC). In this study, we examined the effect of cisplatin on the expression and regulation of PD-L2 in OSCC cell lines and analyzed malignant behavior in PD-L2-expressing cells using colony, transwell and transformation assays. In addition, we examined PD-L2 expression in the tumor tissues of OSCC patients using cytology and tissue microarray methods. In OSCC cell lines, cisplatin treatment upregulated PD-L2 expression, along with that of the drug efflux transporter ABCG2, via signal transducers and activator of transcription (STAT) 1/3 activation. Moreover, PD-L2positive or PD-L2-overexpressing cells demonstrated upregulation in both invasion and transformation ability but not in proliferation compared with PD-L2-negative or PD-L2-silencing cells. PD-L2 expression was also observed in OSCC cells of cytology samples and tissue from OSCC patients. The intensity of PD-L2 expression was correlated with more malignant morphological features in the histological appearance and an invasive pattern. Our findings indicate that cisplatin-upregulated PD-L2 expression in OSCC via STAT1/3 activation and the expression of PD-L2 are likely to be associated with malignancy in OSCC. The PD-L2 expression in cisplatin-resistant OSCC cells may be a critical factor in prognosis of advanced OSCC patients.
Our novel CNT-based PTS up-regulated osteogenesis via activation of heat shock-related molecules, resulting in promotion of mineral deposition in enhanced tooth-extracted sockets.
Transparent DNA/chitosan complex film was prepared from DNA/chitosan complex powder via hydrothermal hot pressing. In this study, we investigated the binding of daunorubicin hydrochloride (DH), proteins adsorption (fibronectin and albumin), mineral deposition, and rat soft-tissue response to the DNA/ chitosan complex film to determine whether this film has potential for use in membranes for bone tissue engineering. The binding ratio of DH to DNA/chitosan complex film was very close to the excision number of 3.7 for the binding of DH by native DNA. This indicated that DNA in the complex did not denature as a result of hot pressing. Apatite was formed on the surface of the film after immersion in simulated body fluid. However, quartz crystal microbalance analysis showed that protein absorption to the DNA/chitosan complex was very low. It was found that this film has an affinity for minerals rather than proteins. Although the film remained in an almost unchanged configuration at 21 days after subcutaneous implantation, the response of rat soft tissues to the film was mild. These results suggest that DNA/chitosan complex film has potential for use as a membrane in bone tissue engineering.
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