Detection Of Epstein-Barr Virus DNA Research Articles

Association of subgingival Epstein–Barr virus and periodontitis

Background: The Epstein–Barr virus (EBV) is gaining interest as a possible agent in the etiology of periodontitis. Previous studies have shown controversy on whether EBV DNA in the subgingival periodontal pockets is associated with periodontitis. The present study aimed to seek the potential relationship between EBV and periodontitis. Methods: Samples were taken from gingival crevicular fluid using sterile paper points, and data on sociodemographics, oral health, and periodontal health were recorded. This case-control study of 118 participants included 59 subjects with severe periodontitis and 59 control subjects with mild periodontitis. Quantitative real-time PCR was used to determined EBV load. Results: EBV DNA was detected in 37.3% of the case samples and 18.6% of the control samples. There was no significant difference in a load of EBV DNA between severe and mild periodontitis (p>0.05). The observed load of EBV DNA was up to 4.55x10 5 copies/mL. The detected EBV DNA was significantly associated with the plaque index and the oral hygiene index (p<0.05). Conclusions: Although no significant association was found, EBV may play a role in periodontitis. The real-time PCR methods can be used to monitor the EBV load in gingival crevicular fluid.

Virus-Associated Biomarkers in Oropharyngeal and Nasopharyngeal Cancers and Recurrent Respiratory Papillomatosis.

Nasopharyngeal cancer (NPC) is known to be associated with Epstein–Barr virus (EBV). Pre-treatment and post-treatment detection of plasma cell-free EBV DNA has been shown to be useful as a diagnostic as well as a prognostic factor in NPC. On the other hand, the incidence of human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing. In contrast to cervical cancer, which is classically known to be an HPV-associated malignancy, HPV testing is not clinically applied for OPC, except for p16 immunostaining as a surrogate marker of HPV infection. One of the major characteristics of HPV-associated OPC is its association with a good prognosis compared with non-HPV-associated OPC. However, some patients still have a poor prognosis. Another characteristic of HPV-associated OPC is the distinct risk factor of high sexual activity. Establishing a biomarker for the prediction of the prognosis before and/or after initial treatment, as well as for diagnosis in populations at high risk, is of marked interest. With this background, HPV DNA detection in plasma and oral rinses has become an area of focus. In this review, the current significance of HPV DNA detection in plasma and oral rinse samples, as well as serum HPV antibody levels, is evaluated.

Association of subgingival Epstein–Barr virus and periodontitis

Background: The Epstein–Barr virus (EBV) is gaining interest as a possible agent in the etiology of periodontitis. Previous studies have shown controversy on whether EBV DNA in the subgingival periodontal pockets is associated with periodontitis. The aim of the present study was to seek the potential relationship between EBV and periodontitis. Methods: Data on socio-demographics, oral health, and periodontal health were recorded, and samples were collected from gingival crevicular fluid, using sterile paper point. This case–control study of 118 participants included 59 subjects with severe periodontitis and 59 control subjects with mild periodontitis. The EBV load was determined by quantitative real-time PCR. Results: EBV DNA was detected in 37.3% of the case samples and in 18.6% of the control samples. There was no significant difference in the load of EBV DNA between severe and mild periodontitis (p&gt;0.05). The observed load of EBV DNA was up to 4.55x105 copies/mL. The detected EBV DNA was significantly associated with the plaque index and the oral hygiene index (all p&lt;0.05). Conclusions: A significant association was not found, but EBV might contribute to periodontitis. Gingival crevicular fluid is useful for monitoring the EBV load by the real-time PCR technique.

Limited utility of the HScore in detecting secondary haemophagocytic lymphohistiocytosis in COVID‐19

Limited utility of the HScore in detecting secondary haemophagocytic lymphohistiocytosis in COVID‐19

Nomograms for predicting survival outcomes in intensity-modulated radiotherapy era of nasopharyngeal carcinoma: A study based on Epstein-Barr virus DNA biological responses.

Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity-modulated radiotherapy (IMRT) era, which requires patient-specific reestimation of survival outcomes in modern health care. A total of 488 detectable pre-treatment Epstein-Barr virus (EBV) DNA patients (stage II-IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163). Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression-free survival (PFS). Both nomograms included age, T classification, N classification, post-IC EBV DNA, and CC. Predictions correlated well with observed 3-/5-year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69-0.86) for OS and 0.742 (95% CI 0.65-0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low- and high-risk groups. The validated nomograms provided useful prediction of OS and PFS for detectable pre-treatment EBV DNA patients with NPC in IMRT era.

Circulating cell\u2010free epstein\u2013barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

BackgroundThe identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC.MethodsThe present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR.ResultsOverall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients.ConclusionsThe results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

Significance of boost dose for T4 nasopharyngeal carcinoma with residual primary lesion after intensity-modulated radiotherapy.

Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT). 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4-6.75Gy was delivered to the residual lesions in 2-3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein-Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification. Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor. The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell–directed therapy

AbstractX-linked lymphoproliferative disease (XLP) is a congenital immunodeficiency that is characterized by an abnormal immune response to primary Epstein-Barr virus (EBV) infection. After EBV exposure, affected patients often develop fulminant infectious mononucleosis (FIM), a life-threatening condition marked by the uncontrolled expansion and activation of T and B lymphocytes and macrophages. We hypothesized that the rapid elimination of B cells immediately following EBV exposure might reduce the severity of primary EBV infection in patients with XLP. To test this possibility, we administered the anti-CD20 antibody rituximab to 2 patients who presented with acute infection. Following treatment, both patients exhibited a complete resolution of symptoms and no longer demonstrated detectable EBV DNA within circulating lymphocytes. Moreover, neither patient has developed FIM or lymphoma in more than 2 years of follow-up. These data suggest that the pre-emptive use of B-cell–directed therapy may reduce the morbidity and mortality of primary EBV infection in XLP-affected individuals.

Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor ubiquitously associated with the Epstein‐Barr virus (EBV), which is highly prevalent in South China, Southeast Asia, and North Africa. Despite being a highly radio‐sensitive and treatable cancer, a majority of NPC patients are diagnosed in their advanced stage, and locoregional and distant relapses following definitive treatment contribute largely to cancer‐specific mortality among these patients. Given that EBV‐driven NPC is the predominant variant seen in endemic regions, various EBV detection methods have been developed and are utilized in screening, prognostication, and post‐treatment surveillance of NPC patients. While the Immunoglobulin A (IgA) serology assay is the most extensively studied EBV detection method, the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening, prognostication, and detection of distant relapse. Furthermore, there is emerging evidence on the use of circulating tumor cells, microRNAs, DNA hypermethylation, and combination assays in various clinical scenarios. Herein, this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC. Specifically, the recent advances, clinical evidence, and challenges associated with the clinical application of EBV liquid biopsies in population screening, prognostication, and surveillance of NPC are presented.

Detection of Epstein-Barr Virus DNA in Gastric Biopsies of Pediatric Patients with Dyspepsia.

In this study, we assessed the presence of Epstein-Barr virus (EBV) in gastric samples derived from pediatric patients with dyspeptic symptoms, aiming to understand whether EBV participates in the development of early gastric lesions influencing chronic inflammation, in conjunction with the Helicobacter pylori (Hp) bacterium. We analyzed EBV load in 236 gastric biopsies derived from 186 pediatric patients with chronic dyspepsia and compared it with EBV serology, Hp load and serology, and with immune cell infiltration. We found that 7.5% of patients were positive for EBV load, ranging from 240 to 29,685 genomic copies/μg of DNA. Hp genomic sequences were found in 24.7% of patients. EBV positive samples did not correlate with Hp status and were characterized by absent to moderate immune cell infiltration. To our knowledge, this is the first study addressing EBV load in the stomach in a large cohort of pediatric patients with dyspeptic symptoms, providing evidence of EBV localization in the gastric mucosa in early inflammatory lesions. The lack of correlation between EBV and both Hp infection and inflammation is perhaps explained by independent pathogenic mechanisms or because of the randomness of the gastritis sampling. This is also supported by a moderate association between EBV load and serology.

Presence of asymptomatic cytomegalovirus and Epstein--Barr virus DNA in blood of persons with HIV starting antiretroviral therapy is associated with non-AIDS clinical events.

Even with antiretroviral therapy (ART), persons with HIV (PWH) experience increased morbidity and mortality. Cytomegalovirus (CMV) and Epstein--Barr virus (EBV) co-infections likely exacerbate inflammatory-related diseases. To determine if presence of detectable CMV or EBV DNA in peripheral blood mononuclear cells (PBMC) is associated with non-AIDS events among PWH receiving modern ART. We performed a case--control study of PWH starting ART and HIV-suppressed at year 1 and thereafter, 140 cases who experienced non-AIDS events and 305 matched controls. Events included myocardial infarction, stroke, malignancy, serious bacterial infection or death. Blood samples were studied pre-ART, 1-year post-ART and pre-event. Controls had an event-free follow-up equal or greater than cases. CMV and EBV DNA levels were measured in PBMC. Conditional logistic regression analysis assessed associations and adjusted for relevant covariates; Spearman's correlations compared CMV and EBV DNA levels with other biomarkers. CMV DNA was detected in PBMC of 25% of participants, EBV DNA was detected in more than 90%. Higher EBV DNA levels were associated with increased risk of events at all time points (odds ratio (OR) per one IQR = 1.5-1.7, all P < 0.009). At year 1, detectable CMV DNA was associated with increased risk of events in most adjusted models (OR = 1.4-1.8, P values ranging 0.03-0.17). Higher levels of CMV and EBV DNA correlated with multiple inflammatory markers and lower CD4/CD8 ratio. In PWH starting ART, detection of CMV and EBV DNA in PBMC was associated with development of non-AIDS events. Clinical trials will be needed to understand causal mechanisms and ways to interrupt them.

Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients based on plasma Epstein-Barr virus DNA level after induction chemotherapy.

Purpose: This study aimed to elucidate the optimal cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) according to the post-induction chemotherapy (IC) plasma Epstein–Barr virus (EBV) DNA level.Results: EBV DNA was detected and undetected in 179 and 370 patients, respectively. Of the entire cohort, 73/549 (13.3%) patients received a total CCD ≥ 160 mg/m2 and 476/549 (86.7%) patients, <160 mg/m2. CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, higher 3-year PFS and locoregional relapse-free survival (LRFS) rates were observed in those who received a CCD ≥ 160 mg/m2. Multivariate analysis also showed CCD was an independent prognostic factor for PFS and LRFS in patients with post-IC detectable EBV DNA.Conclusions: CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, those receiving ≥160 mg/m2 CCD showed significantly improved 3-year PFS and LRFS.Methods: NPC patients (549) treated with IC and CCRT were included. Prognosis was assessed using a multivariate Cox proportional hazards model. Furthermore, grade 1–4 toxicities were compared between different CCD groups.

Influence of corticosteroid therapy on viral reactivation in drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms

Drug‐induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characteristically associated with sequential reactivation of herpesviruses, such as human herpesvirus 6 (HHV‐6), Epstein‐Barr virus (EBV), and cytomegalovirus (CMV). Since systemic corticosteroids are thought to result in viral reactivation due to their immunosuppressive effects, we clarified the influence of systemic corticosteroid therapy on viral reactivation in DIHS/DRESS. Viral DNA in peripheral whole blood and serum sIL‐2R level were measured during the disease course in twenty DIHS/DRESS patients. Six of seven patients treated without corticosteroids experienced HHV‐6 viremia associated with elevated serum sIL‐2R levels. In contrast, high‐dose corticosteroids started within 1 week after onset tended to inhibit the occurrence of HHV‐6 reactivation with remarkable suppression of serum sIL‐2R level. Low‐dose corticosteroids or late‐start high‐dose corticosteroids did not suppress occurrence of HHV‐6 viremia and the increase of sIL‐2R levels. HHV‐6 load in the blood was clearly correlated with the serum sIL‐2R level. On the other hand, increased CMV load were found in patients treated with corticosteroids regardless of the start time. The frequency of detection of EBV DNA in peripheral blood was similarly observed in all groups. In conclusion, high‐dose corticosteroids started within 1 week tended to suppress HHV‐6 reactivation through suppression of T cell activation. However, CMV proliferation was promoted by corticosteroids regardless of the start time. These observations suggested that careful consideration should be given to the dose and timing of administration of systemic corticosteroids in the treatment of DIHS/DRESS.

Presence of Epstein-Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation.

The current study aimed to investigate whether cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH). A cross-sectional diagnostic study on CSF fluid samples in patients undergoing lumbar punctures for clinical reasons, to better understand the role of EBV and CMV in the CNS on HIV RNA replication, blood-brain-barrier (BBB) damage and biomarkers of neuronal damage/inflammation. EBV, CMV DNA and HIV RNA were measured on CSF, through real time (RT)-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated blood-brain barrier inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/ml) and aviremic (<50 copies/ml). We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic individuals CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (P < 0.001), higher CSF HIV RNA (P < 0.001) and neopterin levels (P = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (P = 0.056), higher neopterin (P = 0.027) and immune globulins (P = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50 vs. 21.2%, P = 0.036). EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated central nervous system disorders warrants further studies.

Alterations in NKG2A and NKG2C Subsets of Natural Killer Cells Following Epstein–Barr Virus Reactivation in CTLA4Ig-based Haploidentical Transplantation Is Associated With Increased Chronic Graft-Versus-Host Disease

The impact of newer approaches to haploidentical transplantation on Epstein-Barr virus (EBV) is largely unknown. We prospectively evaluated the incidence of EBV reactivation and its impact on transplantation outcomes in 71 patients undergoing haploidentical transplantation with posttransplantation cyclophosphamide in combination with CTLA4Ig-based T-costimulation blockade. Eight patients developed EBV reactivation at a median of 96 days with no incidence of lymphoproliferative disorder. There was no impact of EBV reactivation on acute graft-versus-host disease (GVHD), nonrelapse mortality, progression-free, or overall survival. Despite an overall incidence of 19%, there was a significant increase in chronic GVHD following EBV reactivation (62.5% versus 8%; P = 0.01). NKG2A subset of CD56 natural killer cells increased substantially and persisted following EBV reactivation and chronic GVHD, with a reciprocal decrease in NKG2C subset, whereas the reverse was witnessed in those without chronic GVHD (P < 0.01). Increase in NKG2C subset and a decrease in the NKG2A subset were witnessed within 3 months of subsidence of chronic GVHD. Thus, CTLA4Ig-based haploidentical transplantation was associated with a low incidence of EBV reactivation without EBV-lymphoproliferative disorder. However, EBV reactivation was associated with a sustained alteration in NKG2A and NKG2C subsets of CD56 natural killer cells which might have a pathogenic role in chronic GVHD.

Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.

Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of EBV-related tumors. This study aimed to explore the inner relationship and regulatory mechanism among oxidative stress, EBV reactivation, and radioresistance and to identify new molecular subtyping models and treatment strategies to improve the therapeutic effects of radiotherapy.Methods: ROS, NADP+/NADPH, and GSSG/GSH were detected to evaluate the oxidative stress of cells. 8-OHdG is a reliable oxidative stress marker to evaluate the oxidative stress in patients. Its concentration in serum was detected using an ELISA method and in biopsies was detected using IHC. qPCR array was performed to evaluate the expression of essential oxidative stress genes. qPCR, Western blot, and IHC were used to measure the level of EBV reactivation in vitro and in vivo. A Rta-IgG ELISA kit and EBV DNA detection kit were used to analyze the reactivation of EBV in serum from NPC patients. NPC tumor tissue microarrays was used to investigate the prognostic role of oxidative stress and EBV reactivation. Radiation resistance was evaluated by a colony formation assay. Xenografts were treated with NAC, radiation, or a combination of NAC and radiation. EBV DNA load of tumor tissue was evaluated using an EBV DNA detection kit. Oxidative stress, EBV reactivation, and the apoptosis rate in tumor tissues were detected by using 8-OHdG, EAD, and TUNEL assays, respectively.Results: We found that EBV can induce high oxidative stress, which promotes its reactivation and thus leads to radioresistance. Basically, EBV caused NPC cells to undergo a process of 'Redox Resetting' to acquire a new redox status with higher levels of ROS accumulation and stronger antioxidant systems by increasing the expression of the ROS-producing enzyme, NOX2, and the cellular master antioxidant regulator, Nrf2. Also, EBV encoded driving protein LMP1 promotes EBV reactivation through production of ROS. Furthermore, high oxidative stress and EBV reactivation were positively associated with poor overall survival of patients following radiation therapy and were significant related to NPC patients' recurrence and clinical stage. By decreasing oxidative stress using an FDA approved antioxidant drug, NAC, sensitivity of tumors to radiation was increased. Additionally, 8-OHdG and EBV DNA could be dual prognostic markers for NPC patients.Conclusions: Oxidative stress mediates EBV reactivation and leads to radioresistance. Targeting oxidative stress can provide therapeutic benefits to cancer patients with radiation resistance. Clinically, we, for the first time, generated a molecular subtyping model for NPC relying on 8-OHdG and EBV DNA level. These dual markers could identify patients who are at a high risk of poor outcomes but who might benefit from the sequential therapy of reactive oxygen blockade followed by radiation therapy, which provides novel perspectives for the precise treatment of NPC.

Clinical features and risk factors of ulcerative colitis complicated with EB-viremia

Objective To analyze the clinical features and risk factors of ulcerative colitis (UC)complicated with Epstein-Barr(EB)-viremia and the effect of antiviral therapy on the remission of the symptoms. Methods From April 2014 to January 2018, data of 239 UC patients hospitalized at the Department of Gastroenterology of Second Hospital of Hebei Medical University were collected. The patients were divided into EB-viremia group (trial group, n=43) and non-EB-viremia group (control group, n=196) according to EB virus-DNA detection. The general condition, clinical characteristics and therapeutic efficacy of the two groups were compared. The risk factors and the effect of antiviral therapy on the remission of symptoms of UC complicated with EB-viremia were analyzed. Chi-square test and logistic analysis were used for statistical analysis. Results There were no significant differences in gender, age, clinical type, lesion range, the proportion of patients treated with 5-aminosalicylic acid or corticosteroids, the percentage of patients with diarrhea and bloody stool, the proportion of patients with spontaneous bleeding, platy ulcer and longitudinal ulcer under colonoscopy, the course of disease or Mayo score between the trial group and control group (all P>0.05). The proportions of patients with smoking history and severe disease, treatment with azathioprine and 6-mertocapurine (6-MP), treatrnent with infliximab, symptoms of fever or abdominal pain and deep and large ulcer under colonoscopy in the trial group were all higher than those in the control group, and the differences were all statistically significant (χ2=5.304, 6.608, 6.718, 6.939, 8.783, 4.493 and 5.425, all P 0.05). Conclusions Smoking history and purine treatment are risk factors of UC complicated with EB-viremia. Key words: Colitis, ulcerative; Risk factors; Epstein-Barr virus; Clinical manifestations; Endoscopic features

Comparison of TGF-β, IL-10 levels and LMP-1 in gastric and oropharyngeal carcinoma associated with EBV infection

Abstract Increasing interest has been focused on the Epstein-Barr Virus (EBV)-associated cancers, including oropharyngeal cancer (OPC) and gastric cancer (GC). Different cytokines, growth factors and proteins take part in oncogenesis. The aim of our study was to generate a comparison of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels, as well as latent membrane protein (LMP-1), Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA) frequency in the serum of patients with GC and OPC. The study involved 50 patients with diagnosed GC and 50 patients with OPC. All studied patients were EBV positive. Fresh-frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. Sera from all individuals were investigated using ELISA tests to detect the presence of EBVCA IgG, EBNA IgG, EA IgG, as well as to determine the levels of IL-10 and TGF-β. The obtained results were subjected to statistical analysis. In patients with GC, the levels of TGF-β and IL-10 were significantly higher than in OPC patients. However, the frequency and level of EBVCA, EBNA and EA in patients with OPC and GC were not significantly different. In contrast, TGF-β and IL-10 levels were significantly higher in EBVaGC, as compared to OPC, suggesting their role in gastric carcinogenesis. The differences in frequency of LMP-1 detection in patients with OPC and GC may suggest different mechanism of oncogenesis. Further studies are required to clarify the role of Epstein-Barr virus in cancer development.

Potential pitfalls in incorporating plasma Epstein-Barr virus DNA in the management of nasopharyngeal carcinoma.

This study identifies potential pitfalls in incorporating plasma Epstein-Barr virus (EBV) DNA into the management of nasopharyngeal carcinoma (NPC). A total of 208 NPC patients without distant metastasis who received radical treatment and had measurements of EBV DNA at baseline, 8 weeks and 26 weeks postradiotherapy were analyzed. Prognostic and predictive values at each time-point were compared. Risk stratification by pretreatment level failed to identify a poor prognostic group. Detectable EBV DNA at 8 weeks and 26 weeks postradiotherapy were both associated with significantly poorer 5-year disease-free survival (HR 0.30, P < .001 and HR 0.03, P < .001, respectively) and overall survival (HR 0.27, P = .009 and HR 0.03, P < .001, respectively). Eighty percentage had detectable EBV DNA at recurrence (53.3% for local only, 100% for regional only, and 100% for distant failure). Posttreatment EBV DNA, particularly at 26 weeks post-radiotherapy, has high prognostic and predictive values. Surveillance endoscopy/imaging are recommended for the detection of local recurrence.

Circulating tumor cells: a valuable marker of poor prognosis for advanced nasopharyngeal carcinoma

PurposeTo evaluate the prognostic value of circulating tumor cells (CTCs) in nasopharyngeal carcinoma (NPC).MethodsCox’s proportional hazards regression models were used to identify whether CTCs was a poor prognostic factor for NPC. Chi-square tests were used to analyze and compare the distribution characteristics of CTCs in NPC. ROC curve was used to estimate the cut-off point of CTCs. Kaplan-Meier survival analyses were used to observe the prognostic value of CTCs alone and in combined with Epstein-Barr Virus DNA (EBV-DNA).ResultsCTCs was confirmed to be an independent risk factor for poor prognosis of NPC by Cox’s regression models that enrolled 370 NPC cases and took age, gender, EBV-DNA and CTCs as variables. The proportion of CTCs in stage IV NPC was statistically different from that in stage III; the cut-off point of CTCs between stage IV (288 cases) and stage III (70 cases) NPC estimated by ROC curve was 0.5. The prognosis of advanced NPC patients became worse with the increase of CTCs count. The combined detection of CTCs and EBV-DNA could better predict the prognosis of NPC compared with the single detection of EBV-DNA.