Predictive Value of ERCC1 mRNA Level from Receiver-Operator Characteristic and Pretreatment EBV-DNA Virus Load in Stage II Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy with Concurrent Cisplatin.

Background: The molecular mechanisms underlying chemoresistance are still poorly understood in nasopharyngeal cancer. The protein expression of ERCC1 in DNA repair genes has been reported related to resistance platinum and predicting treatment outcomes in various malignant carcinomas, but the benefit for predicting outcomes with optimal cutoff value of ERCC1mRNA is controversial. The level of plasma Epstein-Barr virus (EBV) DNA is positively correlated with clinical stages of nasopharyngeal carcinoma (NPC). The predictive value of ERCC1mRNA from receiver-operator characteristic (ROC) and EBV-DNA level for stratified treatment with stage II NPC is exactly unclear. This study aims to assess the predictive value of combined EBV-DNA and ERCC1 in stage II nasopharyngeal cancer (NPC) patients treated with intensity-modulated radiotherapy (IMRT) with concurrent cisplatin, and provide guidance for future stratified treatment. Methods: A total of 86 stage II NPC patients who received IMRT and concurrent cisplatin-based chemotherapy with or without cisplatin-based adjuvant chemotherapy had measurements of ERCC1 mRNA, and pretreatment EBV-DNA levels were analyzed by real-time PCR (RT-PCR). Associations of ERCC1 mRNA and pretreatment EBV-DNA levels with clinical characteristics and survivals were evaluated. Results: Cutoff value of ERCC1 mRNA obtained from ROC curve was used, and there were significant differences in progression-free survival (PFS) and overall survival (OS) and overall response rate (ORR) between high expression group and low expression group (p = 0.021 and 0.030 and 0.000, respectively). Patients with pretreatment EBV-DNA <2000 copies/mL had significantly better PFS and ORR (p = 0.024 and 0.043, respectively) and a marginally significant impact on OS (p = 0.062) than those with pretreatment EBV-DNA ≥2000 copies/mL. Patients were divided into three groups by combination of ERCC1 mRNA and EBV-DNA level: ERCC1 mRNA low expression/pre-EBV-DNA <2000 copies/mL, ERCC1 mRNA low expression/pre-EBV-DNA ≥2000 copies/mL, and ERCC1 mRNA high expression/pre-EBV-DNA ≥2000 copies/mL. There were significant differences in ORR among the three groups (p = 0.005). The median follow-up was 62 months (range 22-84) with a follow-up rate of 90.70%. In these groups by combination of ERCC1 mRNA and EBV-DNA level, 1, 3, 5-year OS were 100%, 100%, 100%; 100%, 94.1%, 90.9%; and 100%, 85%, 72.9%, respectively (p = 0.038); 1, 3, 5-year PFS were 100%, 100%, 100%; 97.1%, 91.2%, 84.8%; and 95%, 85%, 71.4%, respectively (p = 0.028). Multivariate analysis showed that combination of ERCC1 mRNA and EBV-DNA levels remained independent prognostic factor but not ERCC1 mRNA and EBV-DNA alone. Conclusions: Combined ERCC1 mRNA and pre-EBV-DNA is a better prognostic biomarker in stage II NPC patients treated with concurrent chemoradiation. Patients with ERCC1 mRNA high expression/pre-EBV-DNA ≥2000 copies/mL may benefit from more aggressive treatment.

Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells.

Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP. Here, we detected a robust increase of the levels of syncytin-1 and CRP in schizophrenia patients, and displayed a positive correlation and marked consistency between expressions of syncytin-1 and CRP in schizophrenia patients. Furthermore, overexpression of syncytin-1 significantly elevated the levels of CRP, TLR3, and IL-6 in both human microglia and astrocytes. TLR3 deficiency impaired the expressions of CRP and IL-6 induced by syncytin-1. Importantly, we observed a cellular co-localization and a direct interaction between syncytin-1 and TLR3. Additionally, knockdown of IL-6 inhibited the syncytin-1-induced CRP expression. Thus, the totality of these results showed that viral protein syncytin-1 could trigger the activation of CRP, which might explain the elevated CRP in sterile inflammation and exhibit a novel mechanism for regulation of inflammation by syncytin-1 in schizophrenia.

Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses.

Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201+ restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLA-A*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A*0201+ donors with each of these peptides induced peptide-specific CD8+ T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

[Evaluation of direct digital radiography image quality in dentistry].

PURPOSE: To evaluate the quality of direct digital radiograph according to its application in dentistry. METHODS: 1195 patients with dental caries, periodontal diseases, periapical diseases, trauma of teeth or hypodontia were tested with Trophy elitys Radio Visio Graphy(RVG) and the quality of the tests was evaluated at four levels. RESULTS: It was convenient to operate RVG and easy to save the images, which reduced the amount of X-rays. 1587 pictures were taken, among which 92.3% was at level I, 6.3% was at level II,1.14% was at level III and level IV. CONCLUSIONS: The quality of the images at different positions is good, which can meet the requirement for clinical diagnosis. However, the radiography receptor should be improved for better images.