Search

Background: Epstein-Barr virus (EBV) infection is likely to co-occur in pediatric respiratory tract infections (RTIs). Liver injury is the common complication of EBV infection. The detailed risk factors for liver injury in EBV infection remain elusive. We aimed to investigate the incidence, characteristics and potential risk factors for liver injury in EBV infection for early risk prediction. Methods: We retrospectively recruited the pediatric RTIs cases with EBV infection according to a predefined criteria from our hospital between January 2015 and December 2017. We extracted the clinical and laboratory data from the electronical medical records. The impact of age, gender, and various parameters on the liver injury risk was investigated. Univariate logistic regression analysis was performed to analyse the association between clinical/laboratory parameters and liver injury. The related indexes were enrolled in the multivariate logistic regression analysis. Decision curve analysis was used to yield the value of related parameters in predicting liver injury. Receiver operating curve (ROC) analysis was applied to produce the C-index of white blood cell (WBC) count for liver injury. We also tested the non-linear association between WBC count and alanine aminotransferase (ALT). Results: A total of 216 pediatric RTIs with EBV infection were enrolled. EBV infection is more likely to occur during the winter season. Cytomegalovirus infection was independently associated with liver injury in EBV infection (OR = 6.972, 95% CI = 1.648–29.490, p = 0.008). WBC count was independently associated with liver injury in EBV infection (OR = 1.169, 95% CI = 1.051–1.301, p = 0.004). The P interaction value between WBC count and cytomegalovirus was 0.149. The decision curve analysis showed that WBC count had larger area under curve compared with platelet (PLT) and birthweight (BW). ROC analysis yielded the c-index of WBC count: 0.75 and cut-point of 8.3. The turning point of WBC count in its association with ALT was 16.8. The p value before and after the turning point was < 0.001 and 0.123, respectively. Conclusions: Cytomegalovirus co-infection demonstrated 5.972 more times of liver injury risk in EBV infection. WBC count was an independent biomarker for liver injury before the turning point of 16.8 in EBV infection. More attention should be paid to the risk of EBV infection in the winter. Cytomegalovirus infection and WBC count merit attention in the monitoring of possible liver injury in EBV infection among pediatric RTIs. [ABSTRACT FROM AUTHOR]

Background: Use of kinase inhibitors such as dasatinib and imatinib might increase the risk of opportunistic infections, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. However, the effect of sorafenib on EBV and CMV infections remains unclear. The aim of this study was to investigate the effect of sorafenib maintenance post-transplantation on the incidence and mortality of EBV and CMV infections in patients with FLT3-ITD acute myeloid leukemia.Methods: This was a follow-up of our randomized controlled trial undertaken at seven hospitals in China. The primary endpoint was EBV and CMV infections within 3 years post-transplantation. Secondary endpoints included the cumulative incidences of relapse, non-relapse mortality (NRM), overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) at 3 years.Results: Two hundred two patients were assigned to sorafenib maintenance (n=100) or non-maintenance (control, n=102). Median extended follow-up post-transplantation was 36.8 (range, 2.5-67.1) months. The 3-year cumulative incidences of EBV-DNAemia and EBV-associated diseases were 24.0% (95% CI: 16.1-32.8%) and 5.0% (1.8-10.6%) in the sorafenib group, and 24.5% (16.6-33.2%) and 5.9% (2.4-11.6%) in the control group (P=0.937; P=0.771). The 3-year cumulative incidences of CMV-DNAemia and CMV-associated diseases were 56.0% (45.6-65.1%) and 8.0% (3.7-14.4%) in the sorafenib group, and 52.9% (42.7-62.1%) and 8.8% (4.3-15.3%) in the control group (P=0.997; P=0.826). The 3-year cumulative mortality of EBV- and CMV-associated diseases was 0.0% (0.0-0.0%) and 2.0% (0.4-6.4%) in the sorafenib group, and 1.0% (0.1-4.8%) and 2.0% (0.4-6.3%) in the control group (P=0.322, P=0.980). The 3-year cumulative incidences of relapse, NRM, OS, LFS, and GRFS were 13.0%, 11.1%, 79.0%, 75.9%, and 65.8% in the sorafenib group and 34.8%, 12.7%, 61.4%, 52.5%, and 46.6% in the control group, respectively (P<0.001, P=0.656, P=0.005, P<0.001, P=0.003). The reconstitution of T lymphocyte subsets, B lymphocytes, and natural killer cells was similar between the two groups (all P>0.05).Conclusions: Sorafenib maintenance post-transplantation does not increase the incidence and mortality of EBV and CMV infections, demonstrating a favorable safety profile.Trial Registration: ClinicalTrials.gov Identifier: NCT02474290 . Registered on June 14, 2015. [ABSTRACT FROM AUTHOR]

Chronic active Epstein–Barr virus (CAEBV) infection is a rare disease with a high mortality rate. Our study aimed to summarize the clinicopathological characteristics of CAEBV infection in adults and improve knowledge of the disease. Data for 19 adult patients with CAEBV confirmed at our hospital from January 2010 to December 2019 were collected retrospectively. There were 14 males and 5 females, and the median age was 33 years (range 14–83). The main clinical manifestations included recurrent fever (84.2%, 16/19), splenomegaly (89.5%, 17/19), hepatomegaly (73.6%, 14/19), lymphadenopathy (42.1%, 8/19), abnormal liver function (78.9%, 15/19), hemopenia (94.7%, 18/19), and hemophagocytosis (52.6%, 10/19). A total of 22 specimens were collected from 19 patients for histopathology. Most of the biopsy specimens showed lymphocyte infiltration. Immunohistochemical staining and EBV-encoded small RNA (EBER) in situ hybridization were performed for 14 of the 22 samples. CD3 and CD20 staining were positive, with more CD3-positive cells than CD20-positive cells (100%, 14/14), and EBER in situ hybridization was positive in most cases (85.7%, 12/14). More than half of TCR gene rearrangement tests showed monoclonal rearrangement (66.6%, 4/6). Mortality was high, with most CAEBV patients dying during the period from diagnosis to the end of follow-up (12/19, 63%); the median survival time was only 20.75 months. Based on limited data, we consider that CAEBV is a disease with different ages of onset and is a complex and heterogeneous syndrome with features of both immunodeficiency and malignant neoplasms. Furthermore, the prognosis of adult-onset CAEBV appears to be very poor. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a tumor that is commonly found in southern China. NPC has several risk factors, such as infection with the Epstein-Barr virus. However, we know little about the risk factors for eye metastasis (EM) in male patients with NPC. Serum lipids are well recognized as risk factors for cardiovascular disease, and recent studies show that they also have a relationship with the development of NPC. Purpose: We designed the present study to determine whether they were relevant with the development of EM in male NPC patients by detecting the levels of several serum lipids. Methods: A total of 1140 male patients with NPC were enrolled in this retrospective study and we divided them into two groups: the metastasis (EM) group and non-eye metastasis (NEM) group. A variety of serum lipids between the two groups were tested and compared. Results: There were statistical differences in the levels of serum TG and TC between these two groups. Binary logistic regression showed that TG and TC were independent risk factors for EM in male NPC patients with P=0.004 and P<0.001, respectively. The area under the curve of TG and TC were 0.764 and 0.681, respectively, using cutoff values of 0.975 and 3.425 mmol/l, respectively. We found that TG had higher sensitivity and specificity values with 87.5% and 62.7%, respectively, than TC which were 50.0% and 87.2%. Conclusion: TG and TC are potential risk factors for eye metastases in male NPC patients. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in Southern China and southeast Asia, which is characterized by a dense lymphocyte infiltration and a poor prognosis. The emergence of single-cell sequencing represents a powerful tool to resolve tumor heterogeneity and delineate the complex communication among the tumor cells with neighboring stromal and immune cells in the tumor microenvironment (TME). Here, we performed single cell RNA-seq and analyzed tumor cells together with the infiltrating immune cells from three NPC tumor tissues. In our study, the malignant cells display the intra- and inter-tumoral heterogeneity among the individual patients. Analysis of the immune cells reveal the heterogeneous composition of the distinct immune cells and the various functional states of T cells in NPC tumors. Additionally, coupled with the reconstruct of the T cell receptor (TCR) sequences from immune cells full-length single-cell sequence data, we identify the diverse T cell clonotypes and expansion distribution in individual tumors. Overall, we firstly reveal the landscape of tumor and infiltrating immune cells in nasopharyngeal cancer. These results provide deeper insights on the mechanisms of tumor clearance by immune cells in the surrounding microenvironment, which will be helpful in improving the targeted and immune therapies for NPC. [ABSTRACT FROM AUTHOR]

Patients with hemophagocytic lymphohistiocytosis (HLH) have high risk of early mortality. The purpose of this study was to test the hypothesis that the elevated level of serum myoglobin among patients with HLH is associated with disease severity and increased risk of mortality. We retrospectively investigated the serum myoglobin levels from 155 pediatric patients diagnosed with HLH in the Hunan Children's Hospital, China. The levels of myoglobin and creatine kinase at hospital admission among non-survivors and survivors were compared. The myoglobin level was dichotomized for the estimation of hazard ratio (HR) for mortality. Patients who died within 7 and 30 days of hospitalization had significantly higher myoglobin levels than did survivors (p < 0.05). The myoglobin level was negatively associated with the days of survival among non-survivors (Spearman correlation coefficient = - 0.29, p = 0.04). An elevated myoglobin level (> 90 ng/mL) was significantly associated with increased mortality (unadjusted HR = 2.66, 95%CI: 1.41, 5.00, p = 0.0024) and persisted after adjusting for age, Epstein-Barr virus infection, admission department, acute kidney injury, myocardial damage, and shock. In conclusion, an elevated serum myoglobin level was associated with increased risk of early death among pediatric patients with HLH, suggesting the potential of myoglobin to be used as a reference indicator for monitoring and managing of HLH. [ABSTRACT FROM AUTHOR]

Background: Mutations in LPS-responsive and beige-like anchor (LRBA) gene in patients were firstly described to associate with a syndrome of immune deficiency and autoimmunity in 2012. However, there was still no LRBA deficient patient reported in China. Objectives: We present a Chinese patient with heterozygous LRBA gene mutations with his clinical, immunological and genetic features. Methods: Patient's clinical data was collected and analyzed. Laboratory results included lymphocyte subsets analysis and immunoglobulin quantification. Targeted gene capture followed by next-generation sequencing was used to identify the gene mutations, and flow cytometry assay was used to analyze B cell immunophenotyping of this patient. Results: The patient mainly suffered from recurrent respiratory tract infections, EBV-associated lymphoproliferative disease and systemic vasculitis. Heterozygous LRBA gene mutations were identified in the patient, which were inherited from his parents, respectively. B cell immunophenotyping revealed that he had decreased total B cells, bone marrow progenitor B cell subsets (HSC, CLP, Pro-B and Pre-B cells), immature B cells, non-switched memory B cells, switched memory B cells and B1 cell subsets. Besides, he had extremely high level of IgE. Conclusions: Herein, we firstly report a patient with heterozygous LRBA gene mutations in China. LRBA might play an important role in B cell development. [ABSTRACT FROM AUTHOR]

Background: Oral Epstein-Barr virus (EBV) status reflects host EBV activity and potentially links to EBV-associated diseases, however, factors influencing oral EBV loads or reactivation, such as environmental exposures or host factors, are not fully understood.Methods: A 2-stage, multicenter, cross-sectional study of 6558 subjects from 21 administrative cities of southern China and 3 populations from representative geographical areas in China (referred to as the south, north, and northeastern populations) was performed. The relationships between demographical factors and environmental exposures to EBV loads were analyzed by logistic regression models.Results: Current smoking, with a dose-response effect, was found to be strongly associated with higher oral EBV loads in the pooled data, with an odds ratio of 1.58 (95% confidence interval, 1.39-1.79), as well as in each of the separate populations. The odds ratio increased to 3.06 when current smokers in southern China were compared to never smokers in northern China. Additionally, higher oral EBV loads tended to be detected in older participants, male participants, and participants in southern China.Conclusions: This study provided evidence linking the effect of host-environmental factors, particularly smoking, to oral EBV activity. It could strengthen our understanding of the possible causal roles of EBV-related diseases, which may help to prevent or mitigate EBV-associated diseases. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to investigate the histogenesis of lymphoepithelial carcinoma (LEC) and its relationship with Epstein-Barr virus (EBV).Materials and Methods: The expression of EBV was detected using in situ hybridization, and the CK5/6, p63, and p40 expression levels were detected using immunohistochemistry in 45 paraffin-embedded tissues from LEC.Results: In 45 paraffin-embedded LEC tissues from 10 different samples, the positive CK5/6 signals were located in the cell membrane. The positive signals for p63 and p40 were located in the cell nucleus. In all LEC cases, the positive rates of CK5/6, p63, and p40 were 93.3% (42/45), 95.6% (43/45), and 93.3% (42/45), respectively. The positive EBV-encoded RNA (EBER) signals were located in the cell nucleus. In the 45 LEC cases, the expression of EBER was strongly positive with a positive rate of 100% (45/45).Conclusions: LEC is closely related to EBV, and EBV plays an important role in the development of LEC. LEC showed positive squamous cell markers, indicating that the samples contain squamous cell carcinoma (SQCC). LEC is EBV (+) with nonkeratinizing SQCC, and this name better reflects the nature of this disease. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL.Methods: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.Findings: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.Interpretation: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.Funding: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1). [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4 x10-29; PHLA-B-aa-site-116 = 6.56x10 ;PHLA-C-aa-site-156 = 6.8x10-8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. [ABSTRACT FROM AUTHOR]

Background: In China, primary EBV infection occurs during childhood with seroprevalence reaching about 100% by 10 years of age. There are few studies on EBV variants in diseases associated with EBV infection in Chinese children. In this study, we investigated the diversity of the EBV genes (EBNA-1 and LMP-1) and the relationship between EBV variants and the clinical phenotypes in diseases associated with EBV infections in Chinese pediatric cases. Results: The frequencies of EBV type I in the IM, HLH and HL samples were 98.4%, 100% and 95.8%, respectively. Three known EBNA-1 variants were identified, including V-val (all were V-val-v1 sub-variant), P-thr' and V-Leu (MT). The frequency of V-val-v1 was 98.6% in the IM samples, 100% in the HLH samples and 97.1% in the HL samples. There were no significant differences of the distribution of EBNA-1 variants between IM, HLH and HL samples (P > 0.05). Three known LMP-1 variants, including China 1, China 2 and Med, were identified and China 1 was predominant in all groups (IM 88.6%, HLH 100% and HL 100%). The frequency of del-LMP-1 was 88.6% in the IM samples, 100% in the HLH samples and 96.0% in the HL samples. There were no significant differences in the frequency of del-LMP-1 between the IM, HLH and HL samples (P > 0.05). The frequency of XhoI loss was 90.6% in the IM samples, 100% in the HLH samples and 100% in the HL samples, with no significant difference in frequency (P > 0.05). In the EBV type I strain, V-val-v1 variant (EBNA-1) was linked with China1 variant (LMP-1) in 88.9% of the IM samples, 100% of the HLH samples and 80.0% of the HL samples in this study. Conclusions: Type I EBV was the most prevalent subtype EBV in Chinese pediatric cases and V-val-v1 (EBNA-1) and China1 (LMP-1) variants were the most dominant variants. There was a strong linkage between V-val-v1 (EBNA-1) variant and China1 (LMP-1) variant in type I EBV. The sequence variation in EBV genes may represent a geographic polymorphism since no preferential associations were found between specific EBV variants and specific diseases in this study. [ABSTRACT FROM AUTHOR]

Background: In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has not been previously investigated. Methodology/Principal Findings: We randomly selected 145 cHL patients with formalin-fixed, paraffin embedded tissue blocks available from 5 hospitals from the Northern part of China. Hematoxylin & Eosin-stained slides were used to reclassify the histological subtypes according to the WHO classification. EBV status was determined by visualization of EBERs in tumor cells using in situ hybridization. Membranous expression of HLA molecules was detected by immunohistochemistry using antibodies HC-10 (class I heavy chain) and anti-β2-microglobulin for HLA class I, and CR3/43 for HLA class II. EBV+ tumor cells were observed in 40% (58/145) of the cHL patients. As expected, the percentage of EBV+ cases was much higher in the mixed cellularity subtype (71%) than in the nodular sclerosis subtype (16%) (p,0.001). Expression of HLA class I was observed in 79% of the EBV+ cHL cases and in 30% of the EBV- cases (p<0.001). For HLA class II, 52% of EBV+ cHL cases were positive, compared to 43% in EBV- cases (p = 0.28). Conclusions: The results in the Northern China population were similar to those in the Caucasian population for HLA class I, but not for HLA class II. [ABSTRACT FROM AUTHOR]

Abstract: Nasopharyngeal carcinoma (NPC) is a unique type of head and neck cancer that is most prevalent in southern China. Previous studies have suggested that genetic susceptibility, environmental carcinogens, and Epstein–Barr virus (EBV) infection contribute to the etiology of NPC. Our group has identified the retinoic acid receptor responder (tazarotene induced) 1 gene (RARRES1; alias TIG1) to be transcriptionally silenced by promoter hypermethylation in ∼90% of NPC cases, suggesting that its inactivation may be important in NPC formation. The aim of this study was to explore the functional role of the RARRES1 protein (alias TIG1) in NPC cells with EBV infection (HK1-EBV) and without (HK1). Cellular proliferation analysis, as measured by 5-bromo-2′-deoxyuridine (BrdU) incorporation, showed that knockdown and overexpression of TIG1 in HK1 led, respectively, to significantly increased (P = 0.005) and reduced (P = 0.027) proportions of BrdU-labeled cells, compared with control cells. In contrast, knockdown or overexpression of TIG1 had no significant effect on cellular proliferation in HK1-EBV cells. Invasion chamber assay showed that TIG1 knockdown in HK1-EBV cells resulted in significant enhancement of invasive capacity of HK1-EBV cells (P = 0.006). HK1 cells were not invasive, regardless of TIG1 status. These findings suggest that TIG1 may play a role in cellular proliferation and invasion in NPC cells and that its function may be dependent on the EBV status. [Copyright &y& Elsevier]

Background: Nasopharyngeal carcinoma is endemic in Southern China, displays a strong relationship with genetic susceptibility and associates with Epstein-Barr virus infection. Toll-like receptor 3 (TLR3) plays an important role in the antivirus response. Therefore, we examined the association between TLR3 gene polymorphisms and NPC susceptibility. Methods: We performed a case-control study of 434 NPC cases and 512 healthy controls matched on age, sex and residence. Both cases and controls are of Cantonese origin from Southern China. Genetic variants in TLR3 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing and four SNPs were genotyped in all samples. Results: Our results showed that allele C for SNP 829A/C increased NPC risk significantly ((p = 0.0068, OR = 1.49, 95%CI:1.10-2.00). When adjusted for age, gender and VCA-IgA antibody titers, the NPC risk was reduced significantly among individuals who carried the haplotype "ATCT" compared to those who carried the most common haplotype "ACCT" (p = 0.0054, OR = 0.028; 95% CI (0.002-0.341). Conclusion: The TLR3 polymorphisms may be relevant to NPC susceptibility in the Cantonese population, although the reduction in NPC risk is modest and the biological mechanism of the observed association merits further investigation. [ABSTRACT FROM AUTHOR]

Background: B7-H4 is among the B7 family members which may serve as a new targetable immune checkpoint molecule. It was reported that high level of serum B7-H4 level may be correlated with lymphoma. Nevertheless, the role of B7-H4 in Epstein-Barr Virus-Positive diffuse large B cell lymphoma (EBV+DLBCL) has not been addressed although it has been suggested that B7-H4 could promote tumor growth and metastatic progression in certain cancers. Methods: Between January 2005 and November 2017 at the department of Hematology, Shanghai Jiao Tong University School of Medicine affiliated Shanghai General Hospital 260 DLBCL samples were analyzed for EBV-encoded small RNA (EBV-EBER) by in situ hybridization. The expression level of B7-H4 in DLBCL tumor tissue was evaluated by immunohistochemistry. Furthermore, the role of B7-H4 in DLBCL was further investigated in DLBCL cell line. Results: EBV+DLBCL patients suffered from markedly lower overall survival (OS) and progression-free survival (PFS) rates in our study. We showed that B7-H4 was significantly overexpressed in 16 EBV+-subgroup cases out of 260 DLBCL patients. We further found that EBV infection in lymphoblast cells led to enhanced expression of B7-H4 followed by increased cell viability and reduced apoptosis. In contrast, inhibition of B7-H4 simultaneously impaired cell viability and induced apoptosis. Mechanistically, inhibiting B7-H4 resulted in decreased phosphorylation Erk 1/2 and Akt. Conclusion: Our study reveals a critical role of B7-H4 in EBV+DLBCL development by regulating cell survival and apoptosis through the Erk and Akt signalling pathways. Targetting B7-H4 may be promising in the therapy of EBV+DLBCL. [ABSTRACT FROM AUTHOR]

Background: The clinicopathological features and Epstein-Barr virus (EBV) infection status of lymphoma in children and adolescents in South China is under-researched. South China is a well-known high-incidence area of EBV-associated nasopharyngeal carcinoma. Methods: A cohort of 662 consecutive children and adolescents’ lymphomas was retrospectively analyzed and Epstein-Barr virus encoded RNAs (EBERs) in situ hybridization was performed to detect the EBV infection. Results: The majority (501/662, 75.7%) of lymphomas in children and adolescents was Non-Hodgkin lymphoma (NHL). One hundred sixty one cases (24.3%) were Hodgkin lymphoma (HL). Of the NHL, precursor cell lymphoma, mature B-cell lymphoma and peripheral T/NK-cell lymphoma accounted for 32.0%, 41.1% and 26.9% respectively. The five common subtypes were lymphoblastic lymphoma (32.0%), Burkitt lymphoma (BL) (21.0%), anaplastic large-cell lymphoma (ALCL) (14.2%), diffuse large B-cell lymphoma (DLBCL) (13.8%) and extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (6.2%). EBV infection was detected in 58.9% classical Hodgkin lymphomas (CHLs), 21.4% mature B-cell lymphomas and 52.4% peripheral T/NK-cell lymphomas. Moreover, EBV was associated with high grade NHL including ENKTCL (100.0%), BL (30.5%) and DLBCL (17.6%). Conclusion: The high proportion of peripheral T/NK-cell lymphomas in children and adolescents in South China are presented in this study and compared to western countries due to the high percentage of ENKTCL. ENKTCL is firmly associated with EBV infection, while more than half of HL, a portion of BL and DLBCL are related to EBV infection. This study conclusively demonstrates that EBV infection is more prevalent in children and adolescents with lymphomas in South China compared to western countries. [ABSTRACT FROM AUTHOR]

The article discusses research on the link of tobacco smoke exposure to an elevated risk of nasopharyngeal carcinoma (NPC) as well as Epstein-Barr Virus (EBV) seropositivity in males. Researchers Wei-Hua Jia and colleagues of the Sun Yat-sen University Cancer Center in China used data from male patients living in the Guandong Province to determine potential NPC risk factors and EBV inducers. They found that smoking increases the risk of NPC and is also linked to EBV activation in males.