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  1. Article: Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas.

    Ramayanti, Octavia / Brinkkemper, Mitch / Verkuijlen, Sandra A W M / Ritmaleni, Leni / Go, Mei Lin / Middeldorp, Jaap M

    Cancers

    2018  Volume 10, Issue 4

    Abstract: Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase ... ...

    Abstract Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA. Curcumin, a dietary spice used in Asian countries, is known for its antitumor property and therapeutic potential. Novel curcuminoids that were developed to increase efficacy and bioavailability may serve as oral CLVA adjuvants. We investigated the potential of curcumin and its analogs (curcuminoids) to trigger the EBV lytic cycle in EBVaGC and NPC cells. EBV-reactivating effects were measured by immunoblot and immunofluorescence using monoclonal antibodies specific for EBV lytic proteins. Two of the hit compounds (
    Language English
    Publishing date 2018-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers10040089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Epstein-Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin.

    Ramayanti, Octavia / Juwana, Hedy / Verkuijlen, Sandra A M W / Adham, Marlinda / Pegtel, Michiel D / Greijer, Astrid E / Middeldorp, Jaap M

    International journal of cancer

    2016  Volume 140, Issue 1, Page(s) 149–162

    Abstract: Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA ... ...

    Abstract Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV-DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP-biopsy specimens from patients suspected of having NPC. We observed non-fragmented and Cp-promotor methylated EBV-DNA in both NP brushings and biopsies suggestive of tumor origin. Using quantitative RT-PCR we determined expression levels of 7 critical latent (EBER1, Qp-EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) and 5 lytic (Zta, Rta, TK, PK and VCA-p18) RNA transcripts. Although latent and early lytic RNA transcripts were frequently detected in conjunction with high EBV viral load, in both brushings and biopsies the latent transcripts prevailed and reflected a typical NPC-associated latency-II transcription profile without EBNA2. Late lytic RNA transcripts were rare and detected at low levels mainly in NP brushings, suggestive of abortive viral reactivation rather than complete virus replication. EBV-IgA serology (EBNA1, VCA, Zta) did not correlate to the level of viral reactivation in situ. Overall, viral RNA profiling, DNA fragmentation and methylation analysis in NP brushings and parallel biopsies indicate that NP brush sampling provides a true and robust indicator of NPC tumor presence.
    MeSH term(s) Adult ; Biopsy ; Carcinoma ; DNA Methylation ; DNA, Viral/genetics ; Early Detection of Cancer ; Epstein-Barr Virus Infections/genetics ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Viral ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/physiology ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/diagnosis ; Nasopharyngeal Neoplasms/pathology ; Nasopharyngeal Neoplasms/virology ; Nasopharynx/virology ; Promoter Regions, Genetic ; Prospective Studies ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Viral Load
    Chemical Substances DNA, Viral ; RNA, Messenger ; RNA, Viral
    Language English
    Publishing date 2016-09-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.30418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Vesicle-bound EBV-BART13-3p miRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV-infections.

    Ramayanti, Octavia / Verkuijlen, Sandra A W M / Novianti, Putri / Scheepbouwer, Chantal / Misovic, Branislav / Koppers-Lalic, Danijela / van Weering, Jan / Beckers, Lisa / Adham, Marlinda / Martorelli, Debora / Middeldorp, Jaap M / Pegtel, Dirk Michiel

    International journal of cancer

    2018  Volume 144, Issue 10, Page(s) 2555–2566

    Abstract: Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the ... ...

    Abstract Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus-encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq-based EBV miRNA profiles differ between NPC patients, suggesting inter-tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT-PCR assays that EBV miRNAs BART7-3p, BART9-3p and BART13-3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late-stage NPC patients. Increased levels of BART7-3p, BART9-3p and particularly BART13-3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV-infections reveals a superior diagnostic performance of EBV miRNAs over anti-EBNA1 IgA serology and EBV-DNA load (AUC 0.87-0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV-BART13-3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV-bound BART13-3p in circulation is a promising, NPC-selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Epstein-Barr Virus Infections/genetics ; Epstein-Barr Virus Infections/pathology ; Epstein-Barr Virus Nuclear Antigens/genetics ; Extracellular Vesicles/pathology ; Female ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/virology ; Herpesvirus 4, Human/genetics ; Humans ; Male ; MicroRNAs/genetics ; Middle Aged ; Nasopharyngeal Neoplasms/genetics ; Nasopharyngeal Neoplasms/pathology ; Nasopharyngeal Neoplasms/virology ; Nasopharynx/pathology ; Nasopharynx/virology ; RNA, Viral/genetics ; Young Adult
    Chemical Substances Biomarkers, Tumor ; Epstein-Barr Virus Nuclear Antigens ; MicroRNAs ; RNA, Viral ; EBV-encoded nuclear antigen 1 (O5GA75RST7)
    Language English
    Publishing date 2018-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.31967
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.

    Correia, Samantha / Palser, Anne / Elgueta Karstegl, Claudio / Middeldorp, Jaap M / Ramayanti, Octavia / Cohen, Jeffrey I / Hildesheim, Allan / Fellner, Maria Dolores / Wiels, Joelle / White, Robert E / Kellam, Paul / Farrell, Paul J

    Journal of virology

    2017  Volume 91, Issue 15

    Abstract: Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA ( ... ...

    Abstract Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva samples from people from a wide range of geographic and ethnic backgrounds demonstrates a small percentage of healthy white Caucasian British people carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV is likely to be due to their genes being adjacent to the EBNA3 locus, which is one of the major determinants of the type 1/type 2 distinction. A novel classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny analysis of their protein sequences but is not linked to the type 1/type 2 classification. The BART cluster 2 miRNA region is classified into three major variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA outside the mature miRNA sequences. These SNPs can result in altered levels of expression of some miRNAs from the BART variant frequently present in Chinese and Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants identified here provide a basis for future, more directed analysis of association of specific EBV variations with EBV biology and EBV-associated diseases.
    MeSH term(s) Epstein-Barr Virus Infections/epidemiology ; Epstein-Barr Virus Infections/virology ; Ethnicity ; Genetic Variation ; Genotype ; Geography ; Herpesvirus 4, Human/classification ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Humans ; London ; MicroRNAs/genetics ; Molecular Epidemiology ; Saliva/virology ; Students ; United States ; Viral Proteins/genetics ; Volunteers
    Chemical Substances MicroRNAs ; Viral Proteins
    Language English
    Publishing date 2017-07-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00375-17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7.

    Aromseree, Sirinart / Middeldorp, Jaap M / Pientong, Chamsai / van Eijndhoven, Monique / Ramayanti, Octavia / Lougheed, Sinéad M / Pegtel, D Michiel / Steenbergen, Renske D M / Ekalaksananan, Tipaya

    PloS one

    2017  Volume 12, Issue 1, Page(s) e0169290

    Abstract: Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal ...

    Abstract Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal layer of cervical lesions. In this study, we aimed to determine effects of exosome-transferred EBV-encoded RNAs (EBERs) on keratinocytes expressing human papillomavirus (HPV) 16 E6/E7 (DonorI-HPV16 HFKs). Lipid transfection of in vitro-transcribed EBER1 molecules (ivt EBER1) into DonorI-HPV16 HFKs caused strong induction of interferon (IFN)-related genes and interleukin 6 (IL-6). To gain insights into the physiological situation, monocyte-derived dendritic cells (moDCs), low passage DonorI-HPV16 HFKs and primary keratinocytes were used as recipient cells for internalization of exosomes from wild-type EBV (wt EBV) or B95-8 EBV-infected lymphoblastoid cell lines (LCLs). qRT-PCR was used to determine the expression of EBER1, HPV16 E6/E7, IFN-related genes and IL-6 in recipient cells. The secretion of inflammatory cytokines was investigated using cytometric bead array. Wt EBV-modified exosomes induced both IFN-related genes and IL-6 upon uptake into moDCs, while exosomes from B95-8 EBV LCLs induced only IL-6 in moDCs. Internalization of EBV-modified exosomes was demonstrated in DonorI-HPV16 HFKs, yielding only EBER1 but not EBER2. However, EBER1 transferred by exosomes did not induce IFN-related genes or IL-6 expression and inflammatory cytokine secretion in DonorI-HPV16 HFKs and primary keratinocytes. EBER1 copy numbers in exosomes from wt EBV-infected LCLs were 10-fold higher than in exosomes from B95-8 LCLs (equal cell equivalent), whereas ivt EBER1 was used at approximately 100-fold higher concentration than in exosomes. These results demonstrated that the induction of IFN-related genes and IL-6 by EBER1 depends on quantity of EBER1 and type of recipient cells. High levels of EBER1 in cervical cells or infiltrating dendritic cells may play a role in the inflammation-to-oncogenesis transition of HPV-associated cervical cancer through modulation of innate immune signals.
    MeSH term(s) Blotting, Western ; Cell Line ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Exosomes/genetics ; Exosomes/metabolism ; Human papillomavirus 16/genetics ; Human papillomavirus 16/metabolism ; Humans ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/metabolism ; Interferons/genetics ; Interferons/metabolism ; Keratinocytes/metabolism ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/metabolism ; Papillomavirus E7 Proteins/genetics ; Papillomavirus E7 Proteins/metabolism ; RNA, Viral/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
    Chemical Substances E6 protein, Human papillomavirus type 16 ; Epstein-Barr virus encoded RNA 1 ; Oncogene Proteins, Viral ; Papillomavirus E7 Proteins ; RNA, Viral ; Repressor Proteins ; oncogene protein E7, Human papillomavirus type 16 ; Interferons (9008-11-1)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0169290
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7.

    Sirinart Aromseree / Jaap M Middeldorp / Chamsai Pientong / Monique van Eijndhoven / Octavia Ramayanti / Sinéad M Lougheed / D Michiel Pegtel / Renske D M Steenbergen / Tipaya Ekalaksananan

    PLoS ONE, Vol 12, Iss 1, p e

    2017  Volume 0169290

    Abstract: Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal ...

    Abstract Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal layer of cervical lesions. In this study, we aimed to determine effects of exosome-transferred EBV-encoded RNAs (EBERs) on keratinocytes expressing human papillomavirus (HPV) 16 E6/E7 (DonorI-HPV16 HFKs). Lipid transfection of in vitro-transcribed EBER1 molecules (ivt EBER1) into DonorI-HPV16 HFKs caused strong induction of interferon (IFN)-related genes and interleukin 6 (IL-6). To gain insights into the physiological situation, monocyte-derived dendritic cells (moDCs), low passage DonorI-HPV16 HFKs and primary keratinocytes were used as recipient cells for internalization of exosomes from wild-type EBV (wt EBV) or B95-8 EBV-infected lymphoblastoid cell lines (LCLs). qRT-PCR was used to determine the expression of EBER1, HPV16 E6/E7, IFN-related genes and IL-6 in recipient cells. The secretion of inflammatory cytokines was investigated using cytometric bead array. Wt EBV-modified exosomes induced both IFN-related genes and IL-6 upon uptake into moDCs, while exosomes from B95-8 EBV LCLs induced only IL-6 in moDCs. Internalization of EBV-modified exosomes was demonstrated in DonorI-HPV16 HFKs, yielding only EBER1 but not EBER2. However, EBER1 transferred by exosomes did not induce IFN-related genes or IL-6 expression and inflammatory cytokine secretion in DonorI-HPV16 HFKs and primary keratinocytes. EBER1 copy numbers in exosomes from wt EBV-infected LCLs were 10-fold higher than in exosomes from B95-8 LCLs (equal cell equivalent), whereas ivt EBER1 was used at approximately 100-fold higher concentration than in exosomes. These results demonstrated that the induction of IFN-related genes and IL-6 by EBER1 depends on quantity of EBER1 and type of recipient cells. High levels of EBER1 in cervical cells or infiltrating dendritic cells may play a role in the ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma.

    Feng, Fu-Tuo / Cui, Qian / Liu, Wen-Sheng / Guo, Yun-Miao / Feng, Qi-Sheng / Chen, Li-Zhen / Xu, Miao / Luo, Bing / Li, Da-Jiang / Hu, Li-Fu / Middeldorp, Jaap M / Ramayanti, Octavia / Tao, Qian / Cao, Su-Mei / Jia, Wei-Hua / Bei, Jin-Xin / Zeng, Yi-Xin

    Chinese journal of cancer

    2015  Volume 34, Issue 12, Page(s) 563–572

    Abstract: Background: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the ... ...

    Abstract Background: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.
    Methods: Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations.
    Results: Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.
    Conclusions: Our study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.
    MeSH term(s) Adult ; Aged ; Carcinoma ; Case-Control Studies ; China/epidemiology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/epidemiology ; Epstein-Barr Virus Infections/virology ; Female ; Genetic Association Studies ; Genome, Viral ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Humans ; Incidence ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/epidemiology ; Nasopharyngeal Neoplasms/virology ; Neoplasm Proteins/genetics ; Pilot Projects ; Polymorphism, Single Nucleotide ; Risk Assessment/methods ; Tumor Cells, Cultured ; Viral Proteins/genetics
    Chemical Substances Neoplasm Proteins ; RPMS protein, Human herpesvirus 4 ; Viral Proteins
    Language English
    Publishing date 2015-12-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1045160-2
    ISSN 1944-446X ; 1000-467X
    ISSN (online) 1944-446X
    ISSN 1000-467X
    DOI 10.1186/s40880-015-0073-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group.

    Stoker, Sharon D / Wildeman, Maarten A / Novalic, Zlata / Fles, Renske / van der Noort, Vincent / de Bree, Remco / Braunius, Weibel W / van den Broek, Guido B / Kreike, Bas / Kross, Kenneth W / Juwana, Hedy / Ramayanti, Octavia / Verkuijlen, Sandra A W M / de Boer, Jan Paul / Greijer, Astrid E / Middeldorp, Jaap M / Tan, I Bing

    European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

    2015  Volume 273, Issue 6, Page(s) 1557–1567

    Abstract: This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA ... ...

    Abstract This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51-3.5) and 2.3 (95 % CI 1.72-5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment.
    MeSH term(s) Adult ; Aged ; DNA, Viral/blood ; DNA, Viral/isolation & purification ; Disease-Free Survival ; Early Diagnosis ; Epstein-Barr Virus Infections/diagnosis ; Epstein-Barr Virus Nuclear Antigens/blood ; Female ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms/diagnosis ; Nasopharyngeal Neoplasms/mortality ; Nasopharyngeal Neoplasms/virology ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/virology ; Neoplasm, Residual ; Netherlands ; Prognosis ; Prospective Studies ; Viral Load
    Chemical Substances DNA, Viral ; Epstein-Barr Virus Nuclear Antigens ; EBV-encoded nuclear antigen 1 (O5GA75RST7)
    Language English
    Publishing date 2015-05-01
    Publishing country Germany
    Document type Journal Article ; Multicenter Study
    ZDB-ID 1017359-6
    ISSN 1434-4726 ; 0937-4477
    ISSN (online) 1434-4726
    ISSN 0937-4477
    DOI 10.1007/s00405-015-3620-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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