Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Prevalence of Epstein-Barr virus infection in individuals with nasopharyngeal carcinoma in Malaysia: The first systematic review and meta-analysis

@#Epstein-Barr virus (EBV) was the first herpesvirus associated to human malignancies. Despite the well-known association between EBV and malignancies, the prevalence of EBV infection in Malaysians with malignancies is unknown. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to conduct a systematic review and metaanalysis of published data in this study. Studies reporting the occurrence of EBV infection in Malaysian malignancy patients were searched in electronic databases like PubMed, Scopus, ScienceDirect, and Google Scholar without year or language constraints. The study protocol was filed in PROSPERO (CRD42021273769). A total of 21 studies were included, with 1,036 EBV infection cases among 2,078 malignancy patients. The random-effects model was used to produce summary estimates. The pooled prevalence of EBV infection in Malaysians with malignancy was 36.3% (95% CI, 20.3 – 56.2). When the prevalence estimates were stratified by malignancy type, nasopharyngeal carcinoma has the highest prevalence (90.5%), followed by lymphoma (23.4%), and gastric carcinoma (10.0%). Male patients had a higher cases prevalence and most patients were above the age of 40. In Malaysia, many malignancies are increasingly linked to EBV infection. Screening for EBV infection in malignancy patients is therefore important to determine disease recurrence and metastases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Application of Flow Cytometry Combined Fluorescence in Situ Hybridization to Indentify the Lymphocyte Subtypies with Epstein-Barr Virus Infection / 中国实验血液学杂志

OBJECTIVE@#To establish the technique that take the advantages of flow cytometry combined fluorescence in situ hybridization (Flow-FISH) to identify the Epstein-Barr virus(EBV) infected lymphocyte subtypies in patients' peripheral blood sample.@*METHODS@#Peripheral Blood monocyte from 9 patients with EBV infection enrolled at Children's Hospital in Chongqing Medical University were isolated by Ficoll-paque centrifugal separation. The expressions of EBER1, EBER2 in cell were detected by qRT-PCR. The surface markers of cell were detected by Flow cytometry after staining with their antibodies. The cell was treated Fix-Permeabilization Buffer before hybridization with fluorescent labeled probe at 37 ℃ overnight. The cell status, surface markers and targeted mRNA are detected by flow cytometry and fluorescence microscope.@*RESULTS@#It was optimized that the Fix-Permeabilization Buffer and recipe with 0.2% Tween-20 were picked out as providing a good cell integrity and high resolution of surface markers. Hybridization with 20% formamide and 7% dextran sulfate at 37 ℃ overnight is the optimal hybridization condition as a good hybridization effect, a detectable cell integrity and a high resolution of cell markers under flow cytometry detection. Finally, upon the established Flow-FISH method, lymphocyte subpopulations of the EBV+ cells from cell lines and blood samples of patients were identified successfully.@*CONCLUSION@#A Flow-FISH technology is established, which can be applied in the identification of EBV infected cell subtypes. This research provides a foundmental for its application in clinical test in EBV+ related proliferative diseases.

Association of plasma EBV-DNA copy number and cytokines with B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type / 中华放射肿瘤学杂志

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Progress on biomarkers of EB virus-related posttransplant lymphoproliferative disease / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.

Comparison of EB virus infection between short term and long term use of mycophenolate mofetil for prophylaxis of graft versus host disease after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective:To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Method:Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF ( n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF ( n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result:Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P＞0.05). According to once, the incidence of EBV viremia, defined as EBV＞10 3 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively ( P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [ HR=1.022(95% CI 1.006-1.038),1.600(95% CI 1.059-2.418); P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)( P=0.005) and 10.1% (20/199) versus 8.0% (24/299) ( P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [ HR=1.908(95% CI 1.079-3.373),1.752(95% CI 1.161-2.643); P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P＞0.05) between the two groups. Conclusion:Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.

Research progress on posttransplant lymphoproliferative disease after lung transplantation / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.

Role of EphA2 in pathogenesis of nasopharyngeal carcinoma and its potential as a therapeutic target / 中国肿瘤临床

The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.

Mediastinitis as a complication of Epstein-Barr virus infection: a rare entity

Epstein-Barr virus (EBV) is a member of the herpes virus family that can infect humans. Common manifestations of Epstein-Barr virus infection include fever, lymphadenopathy and pharyngitis with some rare complications including mediastinitis, myocarditis, pancreatitis, acute kidney failure and neurological disorders. Clinical findings along with serological evidences are needed to diagnose the infection. Early investigation for EBV in febrile patients can expedite both diagnosis and treatment.

Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016

Abstract Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1+EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1+EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1+EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p<0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1+EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

Primary subcutaneous lymphomatous granuloma: a case report and review of literature / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features of primary subcutaneous lymphomatoid granulomatosis (LYG). Methods A case of primary subcutaneous LYG was observed by analysis of the clinical, histological features, immunophenotype and molecular pathology with review of the related literature. Results The male patient, 78-year-old, inadvertently found a mass of right axillary for more than 10 days. The boundary of the mass was clear, it seemed to have a capsule, the cut surface was grayish yellow and grayish red, the texture was medium. A large amount of coagulative necrosis was observed in the center of the mass under microscope. The peripheral area showed a morphological change of panniculitis, accompanied by pleomorphic lymphoid infiltration, showed central and vascular destructive infiltration, pathological mitosis was occasionally observed. Immunophenotyping showed that atypical large lymphoid cells expressed CD45 RB, CD20, CD30, while CD3, CD15, CD56, TIA-1, Granzyme B, ALK, CD21, Langerin and CD1 a, S-100 and CK (AE1/AE3) were negative. The proliferation index of Ki-67 ranged from 50％ to 60％. EBER in situ hybridization showed that positive cells were> 20/HPF.Neither acid fast staining nor TB-DNA testing supported tuberculosis. Molecular pathology found clonal Ig K gene rearrangement, TCRB + TCRG gene rearrangement showed the absence of monoclonal proliferating T cell population. Conclusion The primary subcutaneous LYG is a rare tumor. which can be diagnosed by combination of morphology, immunophenotype and molecular pathology.

Effects of Epstein-Barr Virus on Proliferation，Apoptosis and Lipid Metabolism of Gastric Cancer Cells / 中山大学学报(医学科学版)

@# 【Objective】To investigate the effects of Epstein-Barr virus（EBV）on proliferation，apoptosis and lipid metabolism of gastric cancer cells，revealing the pathogenesis and development of EBV-associated gastric carcinoma （EBVaGC）.【Methods】EBV-positive cell line AGS-EBV was established by co-culturing AGS and Akata. Then we compared proliferation，apoptosis and lipid metabolism level between AGS and AGS-EBV cells. CCK-8 assays and Annexin V PE/7-AAD assays were performed to determine the proliferation and apoptosis of gastric cancer cells. Oil-Red O staining and three kinds of kits were used to detect lipid contents including lipid droplets，free fatty acid，triacylglycerol and total cholesterol. Key enzymes of lipogenesis were measured by qRT-PCR.【Results】EBV promoted the proliferation of gastric cancer cell line AGS（F = 23.214，P = 0.001；P values of 24 h，48 h，72 h，96 h and 120 h were 0.007， 0.004，＜0.001，＜0.001 and ＜0.001，respectively），inhibited apoptosis（P values of late and total apoptotic rates were 0.032，< 0.001），and increased intracellular lipid droplets，free fatty acids（P < 0.001），triacylglycerol（P = 0.004） and total cholesterol（P < 0.001）probably via lipogenesis. 【Conclusions】EBV promotes proliferation，inhibits apoptosis， and enhances lipid metabolism of gastric cancer cells.

Early diagnosis and treatment of chronic active Epstein-Barr virus hepatitis / 中国实用内科杂志

Non-hepatotropic viruses such as Epstein-Barr virus(EBV) has high infection rate in the population with biological characteristics of infective-latent-activation. EBV-related diseases including infectious mononucleosis(IM), chronic active EBV infection(CAEBV), EBV-related tumors and other diseases are complex and diverse, and all these can lead to varying degrees of liver damage.CAEBV can induce hepatitis(chronic active Epstein-Barr virus hepatitis, CAEBVH) or even liver failure. The prognosis of the disease is poor and the mortality rate is high. Early identification, diagnosis, and multidisciplinary collaborative treatment of CAEBVH are key to improving the prognosis of patients. This article will review the diagnosis and treatment progress of CAEBVH, and provide references for clinicians to diagnose and treat CAEBVH.

pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma

@#Introduction: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin’s lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway. Materials and Methods:51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement. Results: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression. Conclusion: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.

Advances in immunotherapy of extranodal NK/T cell lymphoma / 中华耳鼻咽喉头颈外科杂志

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin′s lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.

The value of plasma EBV DNA in monitoring the therapeutic effect of nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective@#To investigate the clinical value of plasma EBV DNA in monitoring clinical efficacy in the treatment of nasopharyngeal carcinoma (NPC).@*Methods@#Clinical data of 799 patients initially diagnosed with NPC treated with radical intensity-modulated radiotherapy (IMRT) in our hospital from 2016 to 2017 were analyzed retrospectively. Prior to treatment, the correlation between plasma EBV DNA, clinical stage and tumor progression was analyzed. The relationship between EBV DNA and tumor progression was analyzed after radiotherapy and during follow-up.@*Results@#Before IMRT, the level of EBV DNA was positively correlated with both clinical stage and tumor progression (both P<0.001). At 6 to 8 weeks after IMRT, 19(2.3%) patients positive for plasma EBV DNA obtained the worst prognosis and 14 cases had tumor progression. At 6-8 weeks after IMRT, 9 patients were negative for EBV DNA and 3 cases had tumor progression. The tumor progression rate of patients with undetectable plasma EBV DNA at the end of IMRT was only 8.3%(64/772), and the progression-free survival rate significantly differed among three groups (all P<0.05). The sensitivity, specificity and accuracy rates of persistent positive plasma EBV DNA during follow-up were calculated as 77.6%, 100% and 98.1%, respectively.@*Conclusions@#The level of plasma EBV DNA in patients with NPC is correlated with tumor bearing and tumor progression prior to IMRT. At 6-8 weeks after IMRT, patients who are persistently positive for EBV DNA obtain the worst prognosis and should be given with appropriate adjuvant therapy. The correlation between persistent positive plasma EBV DNA during follow up and tumor progression yields a high accuracy rate, indicating that plasma EBV DNA is a reliable biomarker for monitoring the clinical efficacy after radical treatment for NPC patients.