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1. Li N, Thompson S, Jiang H, Lieberman PM, Luo C: Development of drugs for Epstein-Barr virus using high-throughput in silico virtual screening. Expert Opin Drug Discov; 2010 Dec;5(12):1189-203
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  • [Title] Development of drugs for Epstein-Barr virus using high-throughput in silico virtual screening.
  • IMPORTANCE OF THE FIELD: Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is causally associated with endemic forms of Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease in immunosuppressed individuals.
  • On a global scale, EBV infects > 90% of the adult population and is responsible for ∼ 1% of all human cancers.
  • To date, there is no efficacious drug or therapy for the treatment of EBV infection and EBV-related diseases.
  • AREAS COVERED IN THIS REVIEW: In this review, we discuss the existing anti-EBV inhibitors and those under development.
  • We discuss the value of different molecular targets, including EBV lytic DNA replication enzymes as well as proteins that are expressed exclusively during latent infection, such as EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1.
  • As the atomic structure of the EBNA-1 DNA binding domain has been described, it is an attractive target for in silico methods of drug design and small molecule screening.
  • We discuss the use of computational methods that can greatly facilitate the development of novel inhibitors and how in silico screening methods can be applied to target proteins with known structures, such as EBNA-1, to treat EBV infection and disease.
  • WHAT THE READER WILL GAIN: The reader is familiarized with the problems in targeting of EBV for inhibition by small molecules and how computational methods can greatly facilitate this process.
  • TAKE HOME MESSAGE: Despite the impressive efficacy of nucleoside analogs for the treatment of herpesvirus lytic infection, there remain few effective treatments for latent infections.
  • As EBV latent infection persists within and contributes to the formation of EBV-associated cancers, targeting EBV latent proteins is an unmet medical need.
  • High-throughput in silico screening can accelerate the process of drug discovery for novel and selective agents that inhibit EBV latent infection and associated disease.

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  • (PMID = 22822721.001).
  • [ISSN] 1746-045X
  • [Journal-full-title] Expert opinion on drug discovery
  • [ISO-abbreviation] Expert Opin Drug Discov
  • [Language] eng
  • [Grant] United Kingdom / Wellcome Trust / / 096496; United States / NINDS NIH HHS / NS / R21 NS063905; United States / NINDS NIH HHS / NS / R21 NS063906
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ NIHMS254184; NLM/ PMC3816986
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2. Kast RE: Evidence that amphotericin B mediates reactivation of latent Epstein-Barr virus in Hodgkin's lymphoma allowing cytotoxicity by acyclovir. Yonsei Med J; 2006 Apr 30;47(2):287-90
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  • [Title] Evidence that amphotericin B mediates reactivation of latent Epstein-Barr virus in Hodgkin's lymphoma allowing cytotoxicity by acyclovir.
  • This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy.
  • A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir.
  • A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given.
  • If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others.
  • [MeSH-major] Acyclovir / therapeutic use. Amphotericin B / pharmacology. Drug Synergism. Herpesvirus 4, Human / metabolism. Hodgkin Disease / drug therapy. Hodgkin Disease / virology
  • [MeSH-minor] Anti-Bacterial Agents / pharmacology. Burkitt Lymphoma / virology. Ganciclovir / therapeutic use. Humans. Remission Induction. Tumor Necrosis Factor-alpha / metabolism. Virus Activation

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  • (PMID = 16642564.001).
  • [ISSN] 0513-5796
  • [Journal-full-title] Yonsei medical journal
  • [ISO-abbreviation] Yonsei Med. J.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Anti-Bacterial Agents; 0 / Tumor Necrosis Factor-alpha; 7XU7A7DROE / Amphotericin B; P9G3CKZ4P5 / Ganciclovir; X4HES1O11F / Acyclovir
  • [Other-IDs] NLM/ PMC2687644
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3. Hui KF, Chiang AK: Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death. Int J Cancer; 2010 May 15;126(10):2479-89
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death.
  • In Epstein-Barr virus (EBV)-associated malignancies, the virus is harbored in every tumor cell and persists in tightly latent forms expressing a very limited number of viral latent proteins.
  • Induction of EBV lytic cycle leads to expression of a much larger number of viral proteins, which may serve as potential therapeutic targets.
  • We found that 4 histone deacetylase inhibitors, trichostatin A (TSA), sodium butyrate (SB), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), all significantly induced EBV lytic cycle in EBV-positive gastric carcinoma cells (AGS/BX1, latency II) but only weakly induced in Burkitt lymphoma cells (AK2003, latency I) and did not induce in lymphoblastoid cells (LCLs, latency III).
  • Interestingly, SAHA potently induced viral lytic cycle in AGS/BX1 cells at micromolar concentrations (evidenced by 8-fold increase in viral DNA replication, strong expression of viral lytic proteins and production of infectious virus particles) and mediated enhanced cell death of EBV-positive AGS/BX1 cells when compared with that of EBV-negative AGS cells, possibly related to cell cycle arrest at G2/M phase.
  • Furthermore, SAHA effected strong induction of EBV lytic cycle in nasopharyngeal carcinoma but not in NK lymphoma cells (both expressing EBV latency II pattern), indicating preferential viral lytic induction in epithelial rather than lymphoid malignancies.
  • In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent, which warrants further investigation into its potential application as a novel virus-targeted drug for treatment of EBV-associated epithelial malignancies.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Apoptosis / drug effects. Carcinoma / drug therapy. Carcinoma / virology. Herpesvirus 4, Human / drug effects. Histone Deacetylase Inhibitors / pharmacology. Hydroxamic Acids / pharmacology
  • [MeSH-minor] Blotting, Western. Burkitt Lymphoma / drug therapy. Burkitt Lymphoma / virology. Butyrates / pharmacology. Cell Cycle / drug effects. Cell Line, Tumor. Cell Survival / drug effects. Fluorescent Antibody Technique. Humans. Leukemia / drug therapy. Leukemia / virology. Polymerase Chain Reaction. Stomach Neoplasms / drug therapy. Stomach Neoplasms / virology. Valproic Acid / pharmacology

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  • (PMID = 19816947.001).
  • [ISSN] 1097-0215
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Butyrates; 0 / Histone Deacetylase Inhibitors; 0 / Hydroxamic Acids; 3X2S926L3Z / trichostatin A; 58IFB293JI / vorinostat; 614OI1Z5WI / Valproic Acid
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4. Brennan B: Nasopharyngeal carcinoma. Orphanet J Rare Dis; 2006;1:23
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  • [Title] Nasopharyngeal carcinoma.
  • Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx.
  • 1) squamous cell carcinoma, typically found in the older adult population;.
  • 2) non-keratinizing carcinoma;.
  • 3) undifferentiated carcinoma.
  • Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies.
  • Etiological factors include Epstein-Barr virus (EBV), genetic susceptibility and consumption of food with possible carcinogens--volatile nitrosamines.
  • The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN)-beta therapy.
  • [MeSH-major] Carcinoma / diagnosis. Carcinoma / therapy. Nasopharyngeal Neoplasms / diagnosis. Nasopharyngeal Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Age Distribution. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / diagnosis. Child. Child, Preschool. Global Health. Humans. Incidence. Infant. Infant, Newborn. Neoplasm Staging / methods. Prognosis. Radiotherapy / methods. Young Adult

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  • (PMID = 16800883.001).
  • [ISSN] 1750-1172
  • [Journal-full-title] Orphanet journal of rare diseases
  • [ISO-abbreviation] Orphanet J Rare Dis
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 36
  • [Other-IDs] NLM/ PMC1559589
  • [General-notes] NLM/ Original DateCompleted: 20070719
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5. Bibas M, Antinori A: EBV and HIV-Related Lymphoma. Mediterr J Hematol Infect Dis; 2009;1(2):e2009032

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] EBV and HIV-Related Lymphoma.
  • The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART) (1).
  • Epstein-Barr virus (EBV), a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients.
  • It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL), Hodgkin disease (HD), systemic non Hodgkin lymphoma (NHL), primary central nervous system lymphoma (PCNSL), nasopharyngeal carcinoma (NC).
  • Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy.
  • Detailed understanding of the EBV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein.

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  • (PMID = 21416008.001).
  • [ISSN] 2035-3006
  • [Journal-full-title] Mediterranean journal of hematology and infectious diseases
  • [ISO-abbreviation] Mediterr J Hematol Infect Dis
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC3033170
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6. Plaza G, Fogué L, Martínez San Millán J, Martínez Vidal A, Bellas C: [Diagnostic evaluation of nasopharyngeal carcinoma: role of Epstein-Barr virus]. An Otorrinolaringol Ibero Am; 2002;29(1):71-91
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  • [Title] [Diagnostic evaluation of nasopharyngeal carcinoma: role of Epstein-Barr virus].
  • [Transliterated title] Evaluación diagnóstica del carcinoma nasofaríngeo: papel del virus de Epstein-Barr.
  • We present a retrospective series of 27 nasopharyngeal carcinomas, selected from those attended at Ramón y Cajal Hospital between 1977 and 1996, with the aim of review the role of the study of Epstein-Barr virus in the diagnostic process of nasopharyngeal carcinoma.
  • Radiotherapy was employed in all cases, helped by chemotherapy in 20% of them.
  • Of 27 cases of nasopharyngeal carcinoma 4 were differentiated (type I), 2 moderately differentiated (type II) and 22 undifferentiated (type III).
  • While LMP-1 was only expressed by 41% of cases, PCR detected Epstein-Barr virus genome in 26 cases (96%) and in situ hybridization for EBERs was positive in all cases.
  • Thus, all nasopharyngeal carcinomas were related to Epstein-Barr virus.
  • Expression of LMP-1 seemed to worse the prognosis of nasopharyngeal carcinoma.
  • [MeSH-major] Carcinoma. Nasopharyngeal Neoplasms

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  • (PMID = 11962004.001).
  • [ISSN] 0303-8874
  • [Journal-full-title] Anales otorrinolaringológicos ibero-americanos
  • [ISO-abbreviation] An Otorrinolaringol Ibero Am
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Spain
  • [Number-of-references] 60
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7. Comito MA, Sun Q, Lucas KG: Immunotherapy for Epstein-Barr virus-associated tumors. Leuk Lymphoma; 2004 Oct;45(10):1981-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Immunotherapy for Epstein-Barr virus-associated tumors.
  • Epstein-Barr Virus (EBV) is associated with a number of tumors, including lymphomas in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, patients with the acquired immunodeficiency syndrome (AIDS), Burkitt's lymphoma, as well as a subset of patients with nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD).
  • The types of latent EBV infections vary in these tumors, which influences the EBV antigens expressed and ultimately the immunogenicity of tumor cells.
  • Not all EBV associated malignancies are directly related to altered cellular immunity, as is the case with EBV induced lymphoproliferations in immunocompromised patients.
  • Treatment strategies have ranged from restoration of normal cellular immunity, which is generally successful in SOT and HSCT patients, anti-B cell monoclonal antibodies, and conventional chemotherapy and radiation.
  • The fact that these tumors express EBV antigens for which many individuals have high circulating levels of protective cytotoxic T lymphocytes (CTL) has lead to investigation into the applicability of adoptive transfer of EBV specific T cells.
  • Initial success with adoptive immunotherapy for HSCT and SOT patients has lead to current studies examining the feasibility and efficacy of this strategy for other EBV associated tumors, such as NPC and HD.
  • We will review the pathogenesis of these disorders, current therapies, and future investigations aimed at targeting EBV antigen expression on these tumors.
  • [MeSH-major] Herpesvirus 4, Human / immunology. Immunotherapy, Adoptive / methods. Lymphoma / therapy
  • [MeSH-minor] Antigens, Viral / immunology. Antigens, Viral / therapeutic use. Humans. Neoplasms / therapy. Neoplasms / virology. T-Lymphocytes, Cytotoxic / immunology. T-Lymphocytes, Cytotoxic / transplantation. Transplantation

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  • (PMID = 15370241.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Viral
  • [Number-of-references] 77
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8. Paulino AF, Singh B, Carew J, Shah JP, Huvos AG: Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity. Ann Diagn Pathol; 2000 Feb;4(1):7-10
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity.
  • Squamous carcinoma is the most common malignancy of the head and neck, but it rarely occurs in the nasal vestibule.
  • Epstein-Barr virus (EBV) has been detected in and is causally linked to various head and neck tumors, particularly nasopharyngeal carcinoma.
  • The possible role of EBV in squamous carcinoma of the anterior nasal cavity, particularly of the nasal vestibule, has not been previously investigated.
  • Histologic sections from 17 patients with nasal vestibular squamous carcinoma were examined.
  • Material for EBV detection by immunohistochemistry and by in situ hybridization was available in 15 of the 17 cases.
  • Treatment modalities included surgical resection, radiation, chemotherapy, or a combined approach.
  • Three patients developed metastases, one of whom died of disease after 1 year.
  • Epstein-Barr virus was not detected in any of the 15 of 17 cases tested by either immunohistochemistry or by in situ hybridization.
  • Squamous carcinoma of the nasal vestibule is an uncommon cancer that is not causally related to EBV.
  • [MeSH-major] Carcinoma, Squamous Cell / virology. Herpesvirus 4, Human / isolation & purification. Nasal Cavity / virology. Nose Neoplasms / virology

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  • (PMID = 10684374.001).
  • [ISSN] 1092-9134
  • [Journal-full-title] Annals of diagnostic pathology
  • [ISO-abbreviation] Ann Diagn Pathol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antigens, Viral; 0 / EBV-associated membrane antigen, Epstein-Barr virus; 0 / RNA, Viral; 0 / Viral Matrix Proteins
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9. Ueo T, Kashima K, Daa T, Kondo Y, Yokoyama S: Coexistence of Epstein-Barr virus-associated gastric carcinoma with malignant lymphoma: report of two cases. Virchows Arch; 2006 Aug;449(2):215-9
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  • [Title] Coexistence of Epstein-Barr virus-associated gastric carcinoma with malignant lymphoma: report of two cases.
  • Epstein-Barr virus (EBV)-associated gastric carcinoma (EBV-GC) is not rare, accounting for 5 to 18% of all gastric carcinomas.
  • Recently, we encountered two cases of EBV-GC of ordinary histopathological type coexistent with malignant lymphoma.
  • The former was EBV-GC without lymphoma, and antral one was EBV-GC with diffuse large B-cell lymphoma (DLBCL).
  • The other patient was a 49-year-old Japanese man who had received chemotherapy for pelvic DLBCL 3 years earlier.
  • He had EBV-GC with follicular lymphoma in the fundus of the stomach.
  • In both cases, gastric carcinomas were positive for EBV-encoded small RNA by in situ hybridization, whereas the lymphoma cells, infiltrating nonneoplastic lymphocytes, and nonneoplastic epithelial cells were negative.
  • The present cases suggest that focal immunosuppression by adjacent gastric lymphomas might be related to the alteration of the microenvironment and development of EBV-GC.
  • [MeSH-major] Epstein-Barr Virus Infections / complications. Lymphoma / pathology. Neoplasms, Multiple Primary / pathology. Stomach Neoplasms / pathology

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  • (PMID = 16609909.001).
  • [ISSN] 0945-6317
  • [Journal-full-title] Virchows Archiv : an international journal of pathology
  • [ISO-abbreviation] Virchows Arch.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Epstein-Barr virus encoded RNA 1; 0 / RNA, Viral
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10. Abdulkarim B, Sabri S, Zelenika D, Deutsch E, Frascogna V, Klijanienko J, Vainchenker W, Joab I, Bourhis J: Antiviral agent cidofovir decreases Epstein-Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies. Oncogene; 2003 Apr 17;22(15):2260-71
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Antiviral agent cidofovir decreases Epstein-Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies.
  • The Epstein-Barr virus (EBV) is involved in the carcinogenesis of several human cancers such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL).
  • Given the consistent role of EBV in transformation and maintenance of malignant phenotype, antiviral strategies provide an attractive approach to target EBV-expressing cells.
  • In that aim, we have tested the Cidofovir, which is an acyclic nucleoside phosphonate analog known to exert an antiproliferative activity in some human virus-related tumors.
  • Here, we show that Cidofovir induces a downregulation of the EBV oncoprotein LMP1 associated with a decrease of the antiapoptotic Bcl-2 and an increase of the proapoptotic Bax protein in Raji (BL) and C15 (NPC) cells.
  • Using BL cell line BL2 B95-8 (BL2 infected with the B95.8 strain of EBV), we addressed the relation between EBV genome expression and modulation of viral oncoproteins by Cidofovir and/or ionizing radiation (IR).
  • In addition, Cidofovir enhanced the radiation-induced apoptosis and the radiosensitivity through the proteolytic cleavage of death effectors caspase-9 and -3, which was specifically induced by combined treatment in EBV-positive cells compared to their negative counterparts.
  • Furthermore, the combined treatment in nude mice led to a complete tumor remission without increasing toxicity in two human EBV-related cancer xenografts (Raji and C15).
  • These results provide the basis for a novel anticancer strategy to enhance the therapeutic ratio of IR in EBV-related cancers.
  • [MeSH-major] Antiviral Agents / pharmacology. Burkitt Lymphoma / radiotherapy. Carcinoma / radiotherapy. Cytosine / analogs & derivatives. Cytosine / pharmacology. Epstein-Barr Virus Infections / radiotherapy. Gene Expression Regulation, Viral / drug effects. Herpesvirus 4, Human / drug effects. Nasopharyngeal Neoplasms / radiotherapy. Oncogene Proteins, Viral / biosynthesis. Organophosphonates. Organophosphorus Compounds / pharmacology. Proto-Oncogene Proteins / biosynthesis. Proto-Oncogene Proteins c-bcl-2 / biosynthesis. Radiation Tolerance / drug effects. Tumor Virus Infections / radiotherapy
  • [MeSH-minor] Animals. Apoptosis / drug effects. Apoptosis / radiation effects. Caspase 3. Caspase 9. Caspases / metabolism. Cell Division / drug effects. Combined Modality Therapy. Enzyme Activation / drug effects. Enzyme Activation / radiation effects. Female. Genes, bcl-2. Humans. Mice. Mice, Nude. Remission Induction. Tumor Cells, Cultured / drug effects. Tumor Cells, Cultured / metabolism. Tumor Cells, Cultured / radiation effects. Tumor Cells, Cultured / transplantation. Tumor Cells, Cultured / virology. Tumor Stem Cell Assay. Viral Matrix Proteins / biosynthesis. Viral Matrix Proteins / genetics. Xenograft Model Antitumor Assays. bcl-2-Associated X Protein

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  • (PMID = 12700662.001).
  • [ISSN] 0950-9232
  • [Journal-full-title] Oncogene
  • [ISO-abbreviation] Oncogene
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / BAX protein, human; 0 / Bax protein, mouse; 0 / EBV-associated membrane antigen, Epstein-Barr virus; 0 / Oncogene Proteins, Viral; 0 / Organophosphonates; 0 / Organophosphorus Compounds; 0 / Proto-Oncogene Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Viral Matrix Proteins; 0 / bcl-2-Associated X Protein; 8J337D1HZY / Cytosine; EC 3.4.22.- / CASP3 protein, human; EC 3.4.22.- / CASP9 protein, human; EC 3.4.22.- / Casp3 protein, mouse; EC 3.4.22.- / Casp9 protein, mouse; EC 3.4.22.- / Caspase 3; EC 3.4.22.- / Caspase 9; EC 3.4.22.- / Caspases; JIL713Q00N / cidofovir
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11. Comoli P, Pedrazzoli P, Maccario R, Basso S, Carminati O, Labirio M, Schiavo R, Secondino S, Frasson C, Perotti C, Moroni M, Locatelli F, Siena S: Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. J Clin Oncol; 2005 Dec 10;23(35):8942-9
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  • [Title] Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes.
  • PURPOSE: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related malignancy expressing EBV antigens that are possible targets of cell therapy, including latent membrane protein 2 (LMP2).
  • We conducted a clinical trial of EBV-targeted cell therapy with autologous virus-specific cytotoxic T lymphocytes (CTLs) for NPC refractory to conventional treatments.
  • PATIENTS AND METHODS: Ten patients with EBV-related stage IV NPC in progression after conventional radiotherapy and chemotherapy received intravenously autologous EBV-specific CTLs reactivated and expanded ex vivo from peripheral blood lymphocytes through stimulation with EBV-transformed autologous B-lymphoblastoid cell lines (LCL).
  • RESULTS: EBV-specific CTLs could be generated in all patients and were predominantly CD3+/CD8+ T lymphocytes displaying specific killing of autologous EBV-LCL, autologous NPC cells as well as autologous targets bearing the EBV antigen LMP2.
  • Patients received two to 23 infusions of EBV-specific CTLs that were well tolerated with the exception of grade 1 to 2 inflammatory reactions at the tumor site in two cases.
  • Analysis of interferon-gamma-producing cells demonstrated an increased frequency of EBV-specific immunity, with appearance of LMP2-specific responses in four patients, of whom three had clinical benefit.
  • CONCLUSION: Cell therapy with EBV-targeted autologous CTLs is safe, induces LMP-2-specific immunologic responses, and is associated with objective responses and control of disease progression in patients with stage IV NPC resistant to conventional treatments.
  • [MeSH-major] Antigens, Viral / immunology. Herpesvirus 4, Human / immunology. Nasopharyngeal Neoplasms / therapy. T-Lymphocytes, Cytotoxic / immunology
  • [MeSH-minor] Adolescent. Adult. Aged. Cytotoxicity, Immunologic. Disease Progression. Enzyme-Linked Immunosorbent Assay. Humans. Immunotherapy, Adoptive. Male. Middle Aged. Neoplasm Staging. Transplantation, Autologous. Treatment Outcome. Viral Matrix Proteins / immunology

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  • (PMID = 16204009.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Viral; 0 / EBV-associated membrane antigen, Epstein-Barr virus; 0 / Viral Matrix Proteins
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12. Ma B, Hui EP, King A, To KF, Mo F, Leung SF, Kam M, Lo YM, Zee B, Mok T, Ahuja A, Chan AT: A phase II study of patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma and evaluation of plasma Epstein-Barr virus DNA as a biomarker of efficacy. Cancer Chemother Pharmacol; 2008 Jun;62(1):59-64
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  • [Title] A phase II study of patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma and evaluation of plasma Epstein-Barr virus DNA as a biomarker of efficacy.
  • BACKGROUND: The epidermal growth factor receptor (EGFR) is commonly overexpressed in nasopharyngeal carcinoma (NPC) and gefitinib inhibits NPC growth in vitro.
  • METHOD: Patients who progressed after prior platinum-based chemotherapy for recurrent NPC were given gefitinib orally at 500 mg/day at a 28-day cycle.
  • Plasma Epstein-Barr virus (pEBV) DNA levels were obtained at specific intervals.
  • The mean time to progression and overall survival was 2.7 (standard error, SE +/- 0.5 months) and 12 months (SE +/- 1.7 months), respectively.
  • No unexpected drug-related toxicities were seen.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Biomarkers, Tumor / blood. DNA, Viral / blood. Herpesvirus 4, Human / chemistry. Nasopharyngeal Neoplasms / diagnosis. Nasopharyngeal Neoplasms / drug therapy. Quinazolines / therapeutic use

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  • (PMID = 17762933.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Biomarkers, Tumor; 0 / DNA, Viral; 0 / Quinazolines; EC 2.7.10.1 / Receptor, Epidermal Growth Factor; S65743JHBS / gefitinib
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13. Wirth LJ, Fogg M, Wang F, Lorch J, Haddad RI, Posner MR: Epstein-Barr virus (EBV)-specific immunotherapy in nasopharygneal carcinoma (NPC). J Clin Oncol; 2009 May 20;27(15_suppl):6025

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  • [Title] Epstein-Barr virus (EBV)-specific immunotherapy in nasopharygneal carcinoma (NPC).
  • : 6025 Background: Immunotherapy for EBV-associated NPC is intriguing, as viral proteins serve as foreign tumor antigens for cytotoxic T cells (CTLs).
  • EBV-specific CTLs are effective in PTLD, but translating this success to NPC is challenging.
  • We conducted a feasibility study to establish the manufacture and administration of autologous EBV-specific CTLs and explore correlates of response.
  • METHODS: Eligibility criteria include incurable EBV+ NPC, ECOG PS ≤ 1, adequate end-organ function, and no chemotherapy within 2 weeks (wks).
  • CTLs were generated using autologous EBV-transformed B cells to generate autologous EBV-specific CTLs.
  • There were no infusion-related events.
  • Five patients had EBV viral loads (VL) pre- and post-CTLs.
  • CONCLUSIONS: EBV-specific CTLs can be generated from patients with NPC.
  • Factors critical to EBV-specific immunotherapy in NPC remain unclear.

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  • (PMID = 27962433.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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14. Jeyakumar A, Brickman TM, Jeyakumar A, Doerr T: Review of nasopharyngeal carcinoma. Ear Nose Throat J; 2006 Mar;85(3):168-70, 172-3, 184
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  • [Title] Review of nasopharyngeal carcinoma.
  • We review the literature on nasopharyngeal carcinoma that has been published within the past 5 years.
  • Nasopharyngeal carcinoma is a highly morbid disease, and survival is poor.
  • A clear understanding of its etiology is still lacking, but nasopharyngeal carcinoma is widely suspected to be the result of both a genetic susceptibility and exposure to environmental factors or Epstein-Barr virus infection.
  • With no clear cause, treatment is controversial.
  • For example, an optimal radiation regimen has not been determined, reports in the literature regarding the role of chemotherapy for advanced disease are conflicting, and treatment of local recurrences is unsettled.
  • Still, advances in immunologic research and chemotherapy offer hope for better control of the disease.
  • We hope that our assessment of the recent literature will provide otolaryngologists with a more clear understanding of the etiology and management of nasopharyngeal carcinoma.
  • [MeSH-major] Carcinoma. Nasopharyngeal Neoplasms
  • [MeSH-minor] Biomarkers, Tumor / blood. Drug Therapy / methods. Drug-Related Side Effects and Adverse Reactions. Epstein-Barr Virus Infections / complications. Humans. Incidence. Magnetic Resonance Imaging. Nasopharynx / anatomy & histology. Neoplasm Staging. Radiotherapy / adverse effects. Radiotherapy / methods. Tomography, X-Ray Computed

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  • (PMID = 16615599.001).
  • [ISSN] 0145-5613
  • [Journal-full-title] Ear, nose, & throat journal
  • [ISO-abbreviation] Ear Nose Throat J
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
  • [Number-of-references] 23
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15. Guigay J: Advances in nasopharyngeal carcinoma. Curr Opin Oncol; 2008 May;20(3):264-9
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  • [Title] Advances in nasopharyngeal carcinoma.
  • PURPOSE OF REVIEW: Nasopharyngeal carcinoma prognosis is related to its potential locoregional invasion and metastatic spread.
  • Worldwide development of positron emission tomography imaging is changing modalities of staging.
  • Concomitant chemoradiotherapy represents one of the most recent advances in the treatment of nasopharyngeal carcinoma patients, besides intensity-modulated radiation therapy.
  • This review updates these recent advances in diagnosis and treatment of nasopharyngeal carcinoma.
  • RECENT FINDINGS: Recent publications have shown the superiority of fused positron emission tomography/computed tomography over positron emission tomography alone and conventional imaging to do an accurate staging and to impact on patient management.
  • Circulating Epstein-Barr virus DNA load may be a useful prognostic marker in endemic regions.
  • Previous publications have shown that induction chemotherapy with new agents might be promising.
  • Data demonstrating targeted therapies efficacy in metastatic nasopharyngeal carcinoma are limited to date.
  • SUMMARY: Positron emission tomography-computed tomography is replacing conventional imaging in the initial M staging of nasopharyngeal carcinoma.
  • Its usefulness in response evaluation after therapy and its place in the follow-up need to be prospectively evaluated.
  • Cisplatin-based concomitant chemoradiotherapy is now the standard treatment for locally advanced patients.
  • However, incidence of relapses remains high, and new multimodal therapy is needed.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Nasopharyngeal Neoplasms / diagnosis. Nasopharyngeal Neoplasms / therapy. Positron-Emission Tomography. Tomography, X-Ray Computed
  • [MeSH-minor] Biomarkers, Tumor / analysis. Chemotherapy, Adjuvant. Cisplatin / administration & dosage. DNA, Viral / blood. Herpesvirus 4, Human / genetics. Herpesvirus 4, Human / isolation & purification. Humans. Neoadjuvant Therapy. Neoplasm Staging. Prognosis. Radiotherapy, Adjuvant. Radiotherapy, Intensity-Modulated

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  • (PMID = 18391624.001).
  • [ISSN] 1531-703X
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Viral; Q20Q21Q62J / Cisplatin
  • [Number-of-references] 55
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16. Park ES, Do IG, Park CK, Kang WK, Noh JH, Sohn TS, Kim S, Kim MJ, Kim KM: Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection. Clin Cancer Res; 2009 Jan 1;15(1):291-8
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  • [Title] Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection.
  • EBV is detected in approximately 10% of gastric carcinomas and H. pylori induces EBV reactivation in the gastric epithelium.
  • We aimed to evaluate significance of COX-2 in gastric carcinoma occurred in EBV and H. pylori prevalent area.
  • EXPERIMENTAL DESIGN: Tissue microarray samples from 457 gastric carcinoma patients who underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ hybridization for EBV and immunohistochemistry for COX-2 and other gastric carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1).
  • RESULTS: EBV infection was observed in 10.9% of gastric carcinomas and was associated with proximal tumor location, increased numbers of lymph node, and E-cadherin expression (P < 0.01).
  • COX-2 overexpression was closely associated with intestinal histologic type and lower tumor stage (P = 0.01).
  • CONCLUSIONS: EBV infection is not associated with COX-2 expression or survival in gastric carcinoma.
  • Lack of COX-2 expression is an independent prognostic factor in both overall and disease-free survival in gastric carcinoma.
  • Our results indicate that COX-2 may play a role in the progression of gastric carcinoma regardless of EBV infection and is closely associated with histologic differentiation and prognosis.
  • [MeSH-major] Cyclooxygenase 2 / metabolism. Epstein-Barr Virus Infections / complications. Stomach Neoplasms / enzymology. Stomach Neoplasms / virology
  • [MeSH-minor] Chemotherapy, Adjuvant. Female. Humans. Male. Middle Aged. Neoplasm Invasiveness. Prognosis. Tissue Array Analysis


17. Laytragoon-Lewin N, Porwit-MacDonald A, Mellstedt H, Lewin F: Alteration of cellular mediated cytotoxicity, T cell receptor zeta (TcR zeta) and apoptosis related gene expression in nasopharyngeal carcinoma (NPC) patients: possible clinical relevance. Anticancer Res; 2000 Mar-Apr;20(2B):1093-100
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  • [Title] Alteration of cellular mediated cytotoxicity, T cell receptor zeta (TcR zeta) and apoptosis related gene expression in nasopharyngeal carcinoma (NPC) patients: possible clinical relevance.
  • We have investigated apoptosis related gene expression in tumour cells, phenotype and function of blood mononuclear cells at diagnosis in relation to clinical response in three patients with nasopharyngeal carcinoma (NPC).
  • We have focused our study on the Epstein Barr virus latent membrane protein-1 (LMP-1) and Bcl-2 expression in the tumour cells, the essential signal-transducing zeta molecule of T cell receptor (TcR zeta) and cellular mediated cytolysis of the blood mononuclear cells.
  • The carcinoma cells of the patients were Bcl-2 negative.
  • The patient with LMP-1 negative carcinoma cells, down-regulated TcR zeta expression and impaired IL-2 mediated cytolysis, had the worst clinical outcome.
  • Another patient with low apoptotic, highly proliferating and LMP-1 positive carcinoma cells had recurrent disease only in the irradiated area.
  • Interestingly, NPC with high apoptotic and few LMP-1 expressing cells was detected in the patient with a normal level of TcR zeta expression and cytolytic functions in blood mononuclear cells at the time of diagnosis.
  • After combination treatment with chemotherapy followed by radiotherapy, this patient is still alive with complete remission and disease-free at 36 months.
  • Our study suggests that the immunological functions and apoptosis related gene expression in the carcinoma cells may be used as prognostic factors and help in the decision of therapy of patients with nasopharyngeal cancer.
  • [MeSH-minor] Adaptor Proteins, Signal Transducing. Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carrier Proteins / analysis. Cells, Cultured. Cisplatin / administration & dosage. Cytoskeletal Proteins. Cytotoxicity, Immunologic. Fluorouracil / administration & dosage. Humans. Immunity, Cellular. Interferons / therapeutic use. Interleukin-2 / biosynthesis. Intracellular Signaling Peptides and Proteins. Keratins / analysis. LIM Domain Proteins. Male. Middle Aged

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  • (PMID = 10810402.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] GREECE
  • [Chemical-registry-number] 0 / Adaptor Proteins, Signal Transducing; 0 / Carrier Proteins; 0 / Cytoskeletal Proteins; 0 / Interleukin-2; 0 / Intracellular Signaling Peptides and Proteins; 0 / LIM Domain Proteins; 0 / Membrane Proteins; 0 / PDLIM7 protein, human; 0 / Receptors, Antigen, T-Cell; 0 / antigen T cell receptor, zeta chain; 68238-35-7 / Keratins; 9008-11-1 / Interferons; Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
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18. Li G, Li XP, Peng Y, Liu X, Li XH: Effect of inhibition of EBV-encoded latent membrane protein-1 by small interfering RNA on EBV-positive nasopharyngeal carcinoma cell growth. Di Yi Jun Yi Da Xue Xue Bao; 2004 Mar;24(3):241-6
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  • [Title] Effect of inhibition of EBV-encoded latent membrane protein-1 by small interfering RNA on EBV-positive nasopharyngeal carcinoma cell growth.
  • OBJECTIVE: To evaluate the feasibility of using small interfering RNA (siRNA) for selective inhibiting latent membrane protein-1 (LMP1) expression in Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cell line C611, and observe the effects of LMP1 gene silencing on the NPC cell growth.
  • LMP1 siRNA treatment resulted in cell cycle arrest at G(0)-G(1) phase, accompanied by a reduction of cell proliferation by 33%, whereas EBV-negative NPC cells appeared unaffected.
  • CONCLUSIONS: EBV-encoded LMP-1 is vulnerable to RNA interference and selective inhibition of LMP1 suppresses the proliferation of EBV-positive NPC cells, a finding that sheds light on the possible use of RNA interference in further investigations of LMP1 and for therapeutic purposes of EBV-related NPC.
  • [MeSH-major] Nasopharyngeal Neoplasms / therapy. RNA, Small Interfering / pharmacology. Viral Matrix Proteins / antagonists & inhibitors
  • [MeSH-minor] Apoptosis / drug effects. Cell Cycle / drug effects. Cell Division / drug effects. Cell Line, Tumor. Humans. RNA, Messenger / analysis. Transfection

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  • (PMID = 15041532.001).
  • [ISSN] 1000-2588
  • [Journal-full-title] Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA
  • [ISO-abbreviation] Di Yi Jun Yi Da Xue Xue Bao
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / EBV-associated membrane antigen, Epstein-Barr virus; 0 / RNA, Messenger; 0 / RNA, Small Interfering; 0 / Viral Matrix Proteins
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19. Peng PJ, Zhao C, Liao H, Wang FQ, Zhang L: [Correlation between the kinetics of plasma EBV DNA levels and clinical response during treatment in patients with nasopharyngeal carcinoma]. Ai Zheng; 2002 Aug;21(8):817-22
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  • [Title] [Correlation between the kinetics of plasma EBV DNA levels and clinical response during treatment in patients with nasopharyngeal carcinoma].
  • BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma(NPC) is an EB virus (EBV) related cancer.
  • Recently, it was reported that EBV DNA can be detected in NPC patients' plasma or serum.
  • This study was designed to investigate the correlation between the kinetics of plasma EBV DNA levels and clinical response during concomitant chemo-radiotherapy in the locally advanced nasopharyngeal carcinoma patients.
  • METHODS: Blood samples from 20 patients were collected weekly during chemo-radiotherapy(7 times, in total).
  • The first blood sample was collected before treatment.
  • The content of EBV DNA in the samples were detected by using fluorescent quantitative PCR method in the PE Appliance Biosystems 7700 Sequence Detector.
  • RESULTS: Before treatment, plasma EBV DNA was detectable in the plasma of 90% (18/20) NPC patients.
  • Two patients' plasma EBV DNA could not be detected during the whole course of treatment.
  • Among 18 EBV DNA-positive patients, 3 patients had a continuously high EBV DNA and clinical examination after treatment indicated that they had residual tumors.
  • Seven patients'plasma EBV DNA levels had a rapid decline to be undetectable.
  • Eight patients' plasma EBV DNA levels got a slow decline, but the EBV DNA could not be detected at the end of therapy as well.
  • CONCLUSION: Kinetic analysis of plasma EBV DNA during treatment may be a useful tool to monitor the treatment response in NPC patients.
  • [MeSH-major] DNA, Viral / blood. Epstein-Barr Virus Infections / blood. Herpesvirus 4, Human / genetics. Nasopharyngeal Neoplasms / drug therapy
  • [MeSH-minor] Adult. Antineoplastic Agents / therapeutic use. Female. Humans. Kinetics. Male. Middle Aged. Polymerase Chain Reaction. Time Factors

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  • (PMID = 12478884.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / DNA, Viral
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20. Izquierdo-García FM, García-Díez F, Fernández I, Pérez-Rosado A, Sáez A, Suárez-Vilela D, Guerreiro-González R, Benéitez-Alvarez M: Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study. Virchows Arch; 2004 May;444(5):420-5
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  • [Title] Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study.
  • Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression.
  • Both lymphocytes and epithelium were negative for Epstein-Barr virus markers, such as the latent membrane protein and EBER (Epstein-Barr-encoded RNA).
  • The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration.
  • The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis.
  • Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.
  • [MeSH-major] Carcinoma, Squamous Cell / metabolism. Carcinoma, Squamous Cell / pathology. Tumor Suppressor Protein p53 / metabolism. Urinary Bladder Neoplasms / metabolism. Urinary Bladder Neoplasms / pathology
  • [MeSH-minor] Aged. Aged, 80 and over. DNA, Neoplasm / analysis. Disease-Free Survival. Epithelial Cells / metabolism. Epithelial Cells / pathology. Female. Genes, p53 / physiology. Humans. In Situ Hybridization. Male. Polymerase Chain Reaction. Radiotherapy, Adjuvant. T-Lymphocytes, Cytotoxic / metabolism. T-Lymphocytes, Cytotoxic / pathology. Treatment Outcome. Urinary Bladder / surgery

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  • (PMID = 15067546.001).
  • [ISSN] 0945-6317
  • [Journal-full-title] Virchows Archiv : an international journal of pathology
  • [ISO-abbreviation] Virchows Arch.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / DNA, Neoplasm; 0 / Tumor Suppressor Protein p53
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21. Olajos J, Füle E, Erfán J, Krenács L, Stelkovics E, Francz M, Lengyel E, Al-Farhat Y, Esik O: Familial clustering of nasopharyngeal carcinoma in a non-endemic geographical region. Report of two Hungarian cases and a review of the literature. Acta Otolaryngol; 2005 Sep;125(9):1008-13
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Familial clustering of nasopharyngeal carcinoma in a non-endemic geographical region. Report of two Hungarian cases and a review of the literature.
  • The aim of this study was to investigate the familial clustering of nasopharyngeal carcinoma (NPC) in a non-endemic geographical region on the basis of two case reports and a review of the literature.
  • Following an upper respiratory infection, NPC (WHO type III) was detected in a 57-year-old female (Case 1) who presented with nasal symptoms and a year later in her 36-year-old son (Case 2) who presented with enlarged lymph nodes.
  • After initial complete remission, the son experienced regional (cervical) and base of the skull relapses within 2 years, which were treated unsuccessfully by means of radical neck dissection, a second course of radiotherapy and chemotherapy.
  • Epstein-Barr virus (EBV) was detected in pathology sections from both patients.
  • This clinical entity typically has WHO type III histology; it may occur following an upper respiratory tract infection, and EBV-related serological titers were elevated in all 20 investigated cases.
  • The present two cases and the review of the literature strongly suggest that familial clustering of NPC in non-endemic geographical areas may be related to EBV infections.

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  • (PMID = 16193593.001).
  • [ISSN] 0001-6489
  • [Journal-full-title] Acta oto-laryngologica
  • [ISO-abbreviation] Acta Otolaryngol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Norway
  • [Number-of-references] 25
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22. Chi KH, Myers JN, Chow KC, Chan WK, Tsang YW, Chao Y, Yen SH, Lotze MT: Phase II trial of systemic recombinant interleukin-2 in the treatment of refractory nasopharyngeal carcinoma. Oncology; 2001;60(2):110-5
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  • [Title] Phase II trial of systemic recombinant interleukin-2 in the treatment of refractory nasopharyngeal carcinoma.
  • Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated cancer with abundant lymphocyte infiltration histologically.
  • The activity of IL-2 in the treatment of NPC patients is currently unknown.
  • After 7 days, patients were retreated with a second identical cycle of therapy.
  • Those patients who were stable or responding to treatment 5-6 weeks later went on to receive another course (two cycles) of therapy.
  • RESULTS: Fourteen patients received a total of 34 cycles of therapy.
  • Fifty percent had stable disease, 50% had progressive disease after a median of two cycles of therapy.
  • There was one treatment-related death from acute myocardial infarction.
  • Potential mechanisms of the ineffectiveness of IL-2 therapy on NPC patients are discussed.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma / drug therapy. Interleukin-2 / therapeutic use. Nasopharyngeal Neoplasms / drug therapy. Recombinant Proteins / therapeutic use
  • [MeSH-minor] Adult. Aged. Female. Humans. Injections, Intravenous. Male. Middle Aged. Prospective Studies. Treatment Outcome

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  • (PMID = 11244324.001).
  • [ISSN] 0030-2414
  • [Journal-full-title] Oncology
  • [ISO-abbreviation] Oncology
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interleukin-2; 0 / Recombinant Proteins; M89N0Q7EQR / aldesleukin
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23. Angulo-Pernett F, Smythe WR: Primary lymphoepithelioma of the esophagus. Ann Thorac Surg; 2003 Aug;76(2):603-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • This very rare Epstein-Barr virus infection-related malignancy has previously been reported only in patients from Japan.
  • The tumor exhibited classic histologic and immunohistochemical features of lymphoepithelioma, and was successfully treated with neoadjuvant chemotherapy and irradiation followed by surgical resection.
  • [MeSH-major] Carcinoma, Squamous Cell / pathology. Carcinoma, Squamous Cell / therapy. Esophageal Neoplasms / pathology. Esophageal Neoplasms / therapy
  • [MeSH-minor] Biopsy, Needle. Chemotherapy, Adjuvant. Combined Modality Therapy. Esophagectomy / methods. Female. Humans. Immunohistochemistry. Middle Aged. Neoplasm Staging. Prognosis. Radiotherapy, Adjuvant. Treatment Outcome

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  • (PMID = 12902114.001).
  • [ISSN] 0003-4975
  • [Journal-full-title] The Annals of thoracic surgery
  • [ISO-abbreviation] Ann. Thorac. Surg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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24. Au WY, Kumana CR, Lam CW, Cheng VC, Shek TW, Chan EY, Liu R, Kwong YL: Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia. Leuk Res; 2007 Jan;31(1):105-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia.
  • Environmental arsenic exposure predisposes to malignancies, but the risk for therapeutic arsenic is undefined.
  • Three APL patients (de novo, 2; therapy-related, 1) in a cohort of 59 cases given oral-As(2)O(3) for induction and maintenance treatment developed secondary cancers (nasopharyngeal carcinoma, 2; colonic adenocarcinoma, 1) at 16, 36 and 55 months post-As(2)O(3) therapy.
  • Retrospective analysis of biomarkers (Epstein Barr virus serology and quantification, carcinoembryonic antigen) showed the potential presence of cancers before or shortly after As(2)O(3) therapy, suggesting that As(2)O(3) had not initiated these malignancies.
  • [MeSH-major] Adenocarcinoma / chemically induced. Arsenicals / adverse effects. Arsenicals / therapeutic use. Colonic Neoplasms / chemically induced. Leukemia, Promyelocytic, Acute / drug therapy. Nasopharyngeal Neoplasms / chemically induced. Neoplasms / chemically induced. Oxides / adverse effects. Oxides / therapeutic use
  • [MeSH-minor] Adult. Aged. Female. Growth Inhibitors / adverse effects. Growth Inhibitors / therapeutic use. Humans. Male

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  • (PMID = 16725199.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Arsenicals; 0 / Growth Inhibitors; 0 / Oxides; S7V92P67HO / arsenic trioxide
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