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2000 Fiscal Year Final Research Report Summary

Epstein-Barr Virus and Human Cancer

Research Project

Project/Area Number 09253103
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTottori University Faculty of Medicine

Principal Investigator

SAIRENJI Takeshi  Tottori University Faculty of Medicine, Department of Biosignaling, Professor, 医学部, 教授 (10117351)

Co-Investigator(Kenkyū-buntansha) AOZASA Katsuyuki  Osaka University Medical School, Department of Pathology, Professor, 医学部, 教授 (30115985)
EIZURU Yoshito  Kagoshima University School of Medicine, Division of Persisten and Oncogenic Viruses, Professor, 医学部, 教授 (00041351)
HIRAI Kanji  Medical Research Institute, Tokyo Medical and Dental University, Department of Tumor Virology, Professor, 難治疾患研究所, 教授 (00100991)
YANAI Hideo  Yamaguchi University School of Medicine, Department of Internal Medicine, Instructor, 医学部, 講師 (60220175)
FUKAYAMA Masashi  Graduate School of Medicine, Tokyo University, Department of Pathology, Professor, 医学部, 教授 (70281293)
Project Period (FY) 1999 – 2000
KeywordsEpstein-Barr virus (EBV) / EBV associated gastric cancer / EBV associated malignant lymphoma / NK lymphoma / LMP1 / tumorigenesis / EBV positive cell lines / apoptosis
Research Abstract

(l) We demonstrated that EBV associated gastric carcinomas (EBV aGC) represent a clonal proliferation even in gastric mucosa at very early stages of the development. The carcinomas accompany with multiple carcinomas infected with EBV.
(2) We defined that EBV aGC develops in front of chronic atrophic gastritis and associates closely with the gastric mucosa border which is the place for remodel of tubular structures.
(3) We found a new type of EBV aGC which EBV infection is restricted in a small portion of the carcinoma. Two EBV infected cell lines were established from the cancerous and non-cancerous portions, respectively.
(4) We re-evaluated that nasal T/NK cell lymphomas were originated from NK cells and defined the EBV latency type 2 infection in the cells.
(5) We demonstrated that lethal midline granuloma (rhintis gangrenosa progressiva) is originated from NK or T cells and established the cell lines which have the characters of the lymphoma. The all cell lines were EBV positive NK cells and had the abnormality of chromosom 6 accompanied with a deletion of the long arm.
(6) We defined the difference of escaping to cytotoxic T-cell mediated immune surveillance mechanisms between pyothorax-associated lymphoma and nasal natural killer-cell lymphoma.
(7) We characterized EBNA-LP and defined the expression in cytoplasm and the co-localization with a cellular regulating factor HAX-1 and homo-dimelization of EBNA-LP.
(8) We analyzed that the C-terminal regions of LMP-l is critical for the regulation of apoptosis and BHRFinhibits the apoptosis with TRAIL by suppression of caspase 8 activity.

  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Gao,X. et al.: "Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines"Virology. 258. 375-381 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sairenji,T.: "Epstein-Barr virus (EBV) infection and gastric carcinoma : The approach through EBV infected epithelial cell lines"Jpn.J.Infect.Dis.. 52. 110-112 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izawa,M. et al.: "Identification of an alternative form of caspasa-9 in human gastric cancer cell lines : a role of a caspase-9 variant in apoptosis resistance"Apoptosis. 4. 321-325 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanamori et al.: "Differential effects of TPA on cell growth and Epstein-Barr virus reactivation in epithelial cell lines depived from gastric tissues and B cell line Raji"Virus Genes. 20. 113-121 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikuta et al.: "Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children"Microbes and Infection. 2. 1-6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda et al.: "Inhibition of cell growth and Epstein-Barr virus (EBV) reactivation by CD 40 stimutation in EBV-transformed B cells"Viral Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takanashi,M., et al.: "Tumorigenicity of mouse BALB/c 3T3 fibroblast cells which express Epstein-Barr virus-encoded LMP1 and show normal growth phenotypes in vitro is correlated with loss of transforming growth factor-1-mediated growth Innibition"Arch.Virol.. 144. 241-257 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawaguchi K., et al.: "The cellular elongation factor 1 is modified in cells infected with representative alpha-, beta-, or gamma-herpesviruses"J.Virol.. 73. 4456-4460 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka,M., et al.: "Sequence variations of Epstein-Barr virus LMP2A gene in gastric carcinoma in Japan"Virus Genes. 19. 103-111 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shirakata,M. et al.: "Requirement of cellular l : censing process for the dyad symmotry region-dependent replication of the EBV oriP minichromosome"Virology. 263. 42-54 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto,T., et al.: "Epstein-Barr virus (EBV)-infected cells were frequently but dispersely detected in T-cell lymphomas of various types by in situ hybridization with a RNA probe specific to EBV-spesific nuclear antgen 1"Virus Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda,T., et al.: "Detection of lymphocytes productively infected with Epstein-Barr virus in non-neoplastic tonsils"J.gon.Virol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori,S., et al.: "Deletions and Single-basemutations with in the carboxy-termial region of the Datent membrane protein 1 oncogene in Epstein-Barr virus-related gastric cancers of southern Japan"J.Med.Virol.. 57. 152-158 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Herrera・Goepfert,R. et al.: "Epstein-Barr virus-associated gastric carcinoma in Mexico. Analysis of 135 consecutive gastrectomies in two hospitals"Modern Pathol.. 12. 873-878 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinkura,R. et al.: "Epstein-Barr virus specific antibodies in EBV-positive and -negative gastric carcinoma cases in Japan"J.Med.Virol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohsawa,M. et al.: "Immunophenotypic and genotypic characterization of nasal lymphome with polymorphic reticulosismorphology"Int.J.Cancer. 81. 865-870 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno,H. et al.: "HLA-A alleles of patients with pyothorax-associated lymphoma : Delinoation of anti-Spstein-Barr virus (EBV) host immune response during the development of EBV latent antigen-pegitive lympromss"Int.J.Cancer. 82. 630-634 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takakuwa,T. et al.: "No evidence of replication error phenotype in nasal NK/T cell lymphoma"Int.J.Cancer. 84. 623 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miwa,H., et al.: "Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated apoptosis"Free Rad.Res. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno,H. et al.: "Low frequency of HLA-Ao201 allele in patients with Epstein-Barr virus positive nasal lymphomas with polymorphic reticulosis morphology"Int.J.Cancer. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Li,T., et al.: "Mutations of p53 gene in nasal NK/T cell lymphoma"Lab Invest. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaizaki,Y., et al.: "Atrophic gastritis, Spstein-Barr virus infection, and Epstein-Barr virus-associated gastric carcinoms"Gastric Cancer. 2. 101-108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanai,H., et al.: "Epstein-Barr virus infection of the colon with inflammatory bowel desease"Am.J.Gastrienterol.. 94. 1582-1586 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanai,H. et al.: "Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis"J.Clinic.Gastroenterol.. 29. 39-43 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanishi,M.: "The Epstein-Barr virus latent membrane protein 1 (LMP1) enhances TNF alpha-induced apoptosis of intestine 407 epithelial cells : the role of LMP1 C terminal activation regions land2"Virology. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gao, X., Tajima, M.and Sairenji, T.: "Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines."Virology. 258. 375-381 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sairenji, T.: "Epstein-Barr virus (EBV) infection and gastric carcinoma. : The approach through EBV infected epithelial cell lines."Jpn.J.Infect.Dis. 52. 110-112 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izawa, M., Mori, T., Satoh, T., Teramachi, A.and Sairenji, T.: "Identification of an alternative form of caspase-9 in human gastric cancer cell lines : a role of a caspase-9 variant in apoptosis resistance."Apoptosis. 4. 321-325 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanamori, M., Tajima, M., Satoh, Y., Hoshikawa, Y., Miyazawa, Y., Okinaga, K., Kurata, T.and Sairenji, T.: "Differential effects of TPA on cell growth and Epstein-Barr virus reactivation in epithelial cell lines derived from gastric tissues and B cell line Raji."Virus Genes. 20. 113-121 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikuta, K., Satoh, Y., Hoshikawa, Y.and Sairenji, T.: "Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children."Microbes and Infection. 2. 1-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, M., Satoh, T., Takanashi, M., Hirai, K., Ohnishi, E., and Sairenji, T.: "Inhibition of cell growth and Epstein-Barr virus(EBV) reactivation by CD 40 stimulation in EBV-transformed B cells."Viral Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takanashi.M, Jifen Li.J.-F., Shirakata.M, Mori.S.and Hirai.K.: "Tumorigenicity of mouse BALB/c 3T3 fibroblast cells which express Epstein-Barr virus-encoded LMP1 and show normal growth phenotypes in vitro is correlated with loss of transforming growth factor-1-mediated growth inhibition."Arch. Virol.. 144. 241-257 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawaguchi, Y., Matsumura, T., Roizman, B., and Hirai, K.: "The cellular elongation factor 1 is modified in cells infected with representative alpha-, beta-, or gamma- herpesviruses."J.Virol.. 73. 4456-4460 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, M., Kawaguchi, Y., Yokofujita, J., Takage, M., Eishi, Y., and Hirai, K.: "Sequence Variations of Epstein-Barr virus LMP2A gene in gastric carcinoma in Japan."Virus Genes. 19. 103-111 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shirakata, M., Imadome, K., and Hirai, K.: "Requirement of cellular licensing process for the dyad symmetry region-dependent replication of the EBV oriP minichromosome."Virology. 263. 42-54 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, T., Nakamura, Y., Kishimoto, K., Takeuchi, H., Shirakata, M., Mitsuya, T., and Hirai, K.: "Epstein-Barr virus(EBV)-infected cells were frequently but dispersely detected in T -cell lymphomas of various types by in situ hybridization with a RNA probe specific to EBV-specific nuclear antigen 1."Virus Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda, T., Kobayashi, R., Horiuchi, M., Nagata, Y., Hasegawa, M., Mizuno, F., and Hirai, K.: "Detection of lymphocytes productively infected with Epstein-Barr virus in non-neoplastic tonsils."J.Gen.Virol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori S, Itoh T, Tokunaga M, Eizuru Y.: "Deletions and single-basemutations within the carboxy-terminal region of the latent membrane protein 1 oncogene in Epstein-Barr virus-related gastric cancers of southern Japan."J.Med.Virol.. 57. 152-158 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Herrera-Goepfert, R., Reyes, E., Hermandez-Avila, M., Mohar, A., Shinkura, R., Fujiyama, C., Akiba, S., Eizuru, Y., Harada, Y., Tokunaga, M.: "Epstein-Barr virus-associated gastric carcinoma in Mexico. Analysis of 135 consecutive gastrectomies in two hospitals."Modern Pathol. 12. 873-878 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinkura, R., Yamamoto, N., Fujiyama, C., Shinmura, Y., Eizuru, Y., Tokunaga, M.: "Epstein-Barr virus specific antibodies in EBV-positive and -negative gastric carcinoma cases in Japan."J.Med.Virol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohsawa, M., Nakatsuka, S., Kanno, H., Miwa, H., Kojya, S., Harabuchi, Y., Yang, WI., Aozasa, K.: "Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosismorphology."Int.J.Cancer. 81. 865-870 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno, H., Ohsawa, M., Hashimoto, M., Iuchi, K., Nakajima, Y., Aozasa, K.: "HLA-A alleles of patients with pyothorax-associated lymphoma : Delineation of anti-Epstein-Barr virus (EBV) host immune response during the development of EBV latent antigen-positive lymphomas."Int.J.Cancer. 82. 630-634 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takakuwa, T., Aozasa, K.: "No evidence of replication error phenotype in nasal NK/T cell lymphoma."Int.J.Carcer. 84. 623 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miwa, H., Aozasa, K.: "Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated apoptosis."Free Rad. Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno, H., Aozasa K.: "Low frequency of HLA-A 0201 allele in patients with Epstein-Barr virus positive nasal lymphomas with polymorphic reticulosis morphology."Int.J.Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Li, T., Aozasa, K.: "Mutations of p53 gene in nasal NK/T cell lymphoma."Lab Invest. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaizaki, Y., Sakurai, S., Chong, JM., Fudayama, M.: "Atrophic gastritis, Epstein-Barr virus infection, and Epstein-Barr virus-associated gastric carcinoma."Gastric Cancer. 2. 101-108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanai, H., Shimizu, N., Nagasaki, S., Mitani, N.and Okita, K.: "Epstein-Barr virus infection of the colon with inflammatory bowel desease."Am. J.Gastrienterol. 94. 1582-1586 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanai, H., Muakimi, T., Yoshiyama, H., Takeuchi H., Nishikawa, J., Nakamura, H., Okita, K., Miura, O., Shimizu, N.and Takada, K.: "Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis."J.Clinic. Gastroenterol.. 29. 39-43 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawanisi, M.: "The Epstein-Barr virus latent membrance protein 1 (LMPl) enhances TNF alpha-induced apoptosis of intestine 407 epithelial cells : the role of LMPl C-terminal activation regions 1 and 2."Virology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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