1998 Fiscal Year Annual Research Report

EBウイルスとヒト発がん

Research Project

Project/Area Number	09253103
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Research Institution	Tottori University
Principal Investigator	西連寺剛鳥取大学, 医学部, 教授 (10117351)
Co-Investigator(Kenkyū-buntansha)	柳井秀雄山口大学, 医学部., 講師 (60220175) 深山正久自治医科大学, 医学部, 教授 (70281293) 青笹克之大阪大学, 医学部, 教授 (30115985) 榮鶴義人鹿児島大学, 医学部, 教授 (00041351) 平井莞二東京医科歯科大学, 難治研究所, 教授 (00100991)
Keywords	EBウイルス(EBV) / EBV関連胃癌 / EBV関連悪性りンパ腫 / SCIDマウス / LMPl / 腫瘍形成 / EBV感染細胞株 / EBV感染
Research Abstract	1. EBV関連胃癌(EBV胃癌と略)の国際調査:EBV胃癌は、胃癌全体の7〜17%で、ほとんど全ての国および地域で確認された.モスクワ、チリで14%、17%と高頻度で検出された. 2. EBV胃癌の診断及び発生過程: EBV胃癌の内視鏡的特徴、および、発癌過程における慢性萎縮性胃炎・腸上皮化生との関りを解析した。EBV胃癌の多くが胃粘膜萎縮境界近傍から発生し、その背景胃粘膜が萎縮性変化に富んでいた。腸上皮化生の上皮細胞にEBV DNAは検出されなかった。 3. EBV胃癌におけるEBV遺伝子の変異:EBV胃癌に見出されたlatent membrane protein(LMP)-1及びLMP2A遺伝子の欠損および変異は、健康人にも同様に検出された。 4. EBV胃癌由来細胞株:EBV感染上皮系細胞株(GT38,GT39)のEBV感染様式・軟寒天内コロニー形成能及びSCIDマウスへの移植性を検討した。細胞株を接種したSCIDマウスで未分化の腫瘍が形成された。EBV胃癌組織を直接SCIDマウスへ移植し、増殖したKT株はもとの胃癌の性状を維持していた。 5. EBV発癌の分子機構:EBVの腫瘍関連遺伝子蛋白EBNA-LPと相互作用する宿主蛋白hERR-1(human estrogen receptor related protein-1)HAX-1(HSl-associated proteinX-1)を同定した。LMPlによるアポトーシスの調節機構を解析した。 6. EBV関連リンパ腫:pyothorax-associated 1ymphoma(PAL)とnasal lymphoma(NL)の解析をした.2例のPALから性状の異なる2細胞株(OPL-1,OPL-2)を樹立した。EBV陽性NLからNLの性状を有したNK細胞株(SNKl:末梢血由来,SNK6:病変部由来)の樹立に成功した。

Research Products
(31 results)

All Other

All Publications (31 results)

[Publications] Yamauchi,Y.,et al.: "Evaluation of antibodies to the Epstein-Barr virus immediate early gene product,ZBBRA by a new enzyme-linked immunosorbent assay." Intervirology. 41. 000-000 (1998)
[Publications] Sairenji,T.,et al.: "Induction of interleukin-10 on activation of Epstein-Barr virus(EBV)in EBV infected B cell lines." Viral Immunol.11. 221-231 (1998)
[Publications] Satoh,T.,et al.: "The interaction of mitogen-activated protein kinases to Epstein-Barr virus activation in Akata B cells." Virus Genes. 18. 57-64 (1998)
[Publications] Satoh,Y.,et al.: "Effective PCA amplification of Epstein-Barr virus DNA to extracted DNA from paraffin-embedded gastric carcinoma tissues by pretreatment with restriction enzyme or bovine serum albumin." J.Clin.Microbiol.36. 3423-3425 (1998)
[Publications] Takasaka,N.,et al.: "Productive infection of Epstein-Barr virus(EBV)in EBV-genoma-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues." Virology. 247. 152-159 (1998)
[Publications] Hirai,K.,et al.: "Epstein-Barr virus genome in infected cel1s and cancer." Gann Monograph on Cancer Res.45. 29-39 (1998)
[Publications] Shirakata,M.,et al.: "Identification of minimal oriP of Epstein-Barr virus required for DNA replication." J.Biochem.123. 175-181 (1998)
[Publications] Kobayashi,R.,et al.: "Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR." Arch.Virol.143. 803-813 (1998)
[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-β 1-mediated growth inhibition." Arch.Virol.(in press).
[Publications] Mori,S.,et al.: "Delations and single-base mutation within the carboxy-terminal region of the LMP-1 oncogene in EBV-related gastric cancers of southern Japan." J.Med.Virol.57. 152-158 (1999)
[Publications] Machida,H.,et al.: "Anti-herpesvirus activity profile of 4′-rthioarabinofuranosyl purine and uracil nucleosdes and activity of 1-β-D-2′-fluoro-4′-thioarabinofuranosyl guanine and 2,6-diamonopurine against clinical isoiates of human cytomegalovirus." Antiviral.Res.(in press).
[Publications] Murakami,K.,et al.: "A case of large vessel arteritis associated with chronic active Esptein-Barr virus infection." Arth.Rheum.41. 369-373 (1998)
[Publications] Mizuki,M.,et al.: "Natura killer cell-derived large granular lymphocyte of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Esptein Barr virus infection." Am.J.Hematol.59. 309-315 (1998)
[Publications] Hogyo,T.,et al.: "Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.(in press).
[Publications] Ohsawa,M.,et al.: "Rick of non-Hodgkin′s lymphoma in patients with hepatitis C virus infection." Int.J.Cancer.(in press).
[Publications] Iwasaki,Y.,et al.: "Establishment and characterization of a human Esptein-Barr virus-associated gastric carcinoma in SCID mice." J.Virol.72. 8321-8326 (1998)
[Publications] Fukayama,M.,et al.: "Epstein-Barr virus and gastric carcinoma." Gastic Cancer (in press).
[Publications] Nishiwaki,J.,et al.: "Hypoechoic submucosal nodules ; A sign of Epstein-Barr virus-associated early gastric cancer." J.Gastroenterol Hepatol.13. 585-590 (1998)
[Publications] Ohsawa,M.,et al.: "Characteristics of non-Hodgkin's lymphoma complicnted with renal cell malignancies." Oncogene. 55. 482-486 (1998)
[Publications] Kanno,H.,et al.: "Mechanisms for the development of pyothorax-associated lymphoma." Pathol.Int.48. 653-664 (1998)
[Publications] Hongyo,T.,et al.: "Frequent p53 mutation at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.58. 1105-1107 (1998)
[Publications] Kanno,H.,et al.: "Appearance of different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL." Leukemia. 12. 1288-1294 (1998)
[Publications] Kojya,S.,et al.: "Site spectic localization of Epstein-Barr virus in the pharyngeal carcinomas." Jpn.J.Cancer Res.89. 510-515 (1998)
[Publications] Tomita,Y.,et al.: "Plasmacytoma of the gastrointestinal tract in Korea : higher incidence rate than in Japan and EBV-association." Oncology. 55. 27-32 (1998)
[Publications] Yanai,H.,et al.: "Epstein-Barr virus infection of the colon with inflammatory bowel disease." Am.J.Gastroenterol.(in press).
[Publications] Yanai,H.,et al.: "The backgraound atrophic gastristis for Epstein-Barr virus-associated gastrc carcinoma." J.Clin.Gastroenterol. (in press).
[Publications] Tada-Oikawa,S.,et al.: "Generation of hydrogen peroxide precedes loss of mitochondrial membrane potential DNA alkylation-induced apoptosis." FEBS Letters. 442. 65-69 (1999)
[Publications] Yang,W-I.,et al.: "Epstein-Barr virus and gastrointestinal lymphomas in Korea." Yonsei.Med.J.39. 268-276 (1998)
[Publications] Sairenji,T.,et al.: "Immune responses to Epstin-Barr virus infection." In Herpes-Virus and Immunity (Medveczky et a1.,eds) Plenum Press.,NY,USA., (1998)
[Publications] Tokunaga,M.,et al.: "Epstein-Barr virus involvement in gaatric cancer : Biomarker for lymphnode metastnasis" Cancer Epidemiology,Biomarker & Prevention. (in press),
[Publications] Yanai,H.,et al.: "The gastric mucosa surrounding Epstein-Barr virus-associated gastric cancers." In″Gann Monograph on Cancer Research NO.45″ed.Osato T.Japan Scientific Societies Press,Tokyo pp., (1998)

1998 Fiscal Year Annual Research Report

EBウイルスとヒト発がん

Principal Investigator

西連寺 剛 鳥取大学, 医学部, 教授 (10117351)

Research Products

[Publications] Yamauchi,Y.,et al.: "Evaluation of antibodies to the Epstein-Barr virus immediate early gene product,ZBBRA by a new enzyme-linked immunosorbent assay." Intervirology. 41. 000-000 (1998)

[Publications] Sairenji,T.,et al.: "Induction of interleukin-10 on activation of Epstein-Barr virus(EBV)in EBV infected B cell lines." Viral Immunol.11. 221-231 (1998)

[Publications] Satoh,T.,et al.: "The interaction of mitogen-activated protein kinases to Epstein-Barr virus activation in Akata B cells." Virus Genes. 18. 57-64 (1998)

[Publications] Satoh,Y.,et al.: "Effective PCA amplification of Epstein-Barr virus DNA to extracted DNA from paraffin-embedded gastric carcinoma tissues by pretreatment with restriction enzyme or bovine serum albumin." J.Clin.Microbiol.36. 3423-3425 (1998)

[Publications] Takasaka,N.,et al.: "Productive infection of Epstein-Barr virus(EBV)in EBV-genoma-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues." Virology. 247. 152-159 (1998)

[Publications] Hirai,K.,et al.: "Epstein-Barr virus genome in infected cel1s and cancer." Gann Monograph on Cancer Res.45. 29-39 (1998)

[Publications] Shirakata,M.,et al.: "Identification of minimal oriP of Epstein-Barr virus required for DNA replication." J.Biochem.123. 175-181 (1998)

[Publications] Kobayashi,R.,et al.: "Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR." Arch.Virol.143. 803-813 (1998)

[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-β 1-mediated growth inhibition." Arch.Virol.(in press).

[Publications] Mori,S.,et al.: "Delations and single-base mutation within the carboxy-terminal region of the LMP-1 oncogene in EBV-related gastric cancers of southern Japan." J.Med.Virol.57. 152-158 (1999)

[Publications] Machida,H.,et al.: "Anti-herpesvirus activity profile of 4′-rthioarabinofuranosyl purine and uracil nucleosdes and activity of 1-β-D-2′-fluoro-4′-thioarabinofuranosyl guanine and 2,6-diamonopurine against clinical isoiates of human cytomegalovirus." Antiviral.Res.(in press).

[Publications] Murakami,K.,et al.: "A case of large vessel arteritis associated with chronic active Esptein-Barr virus infection." Arth.Rheum.41. 369-373 (1998)

[Publications] Mizuki,M.,et al.: "Natura killer cell-derived large granular lymphocyte of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Esptein Barr virus infection." Am.J.Hematol.59. 309-315 (1998)

[Publications] Hogyo,T.,et al.: "Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.(in press).

[Publications] Ohsawa,M.,et al.: "Rick of non-Hodgkin′s lymphoma in patients with hepatitis C virus infection." Int.J.Cancer.(in press).

[Publications] Iwasaki,Y.,et al.: "Establishment and characterization of a human Esptein-Barr virus-associated gastric carcinoma in SCID mice." J.Virol.72. 8321-8326 (1998)

[Publications] Fukayama,M.,et al.: "Epstein-Barr virus and gastric carcinoma." Gastic Cancer (in press).

[Publications] Nishiwaki,J.,et al.: "Hypoechoic submucosal nodules ; A sign of Epstein-Barr virus-associated early gastric cancer." J.Gastroenterol Hepatol.13. 585-590 (1998)

[Publications] Ohsawa,M.,et al.: "Characteristics of non-Hodgkin's lymphoma complicnted with renal cell malignancies." Oncogene. 55. 482-486 (1998)

[Publications] Kanno,H.,et al.: "Mechanisms for the development of pyothorax-associated lymphoma." Pathol.Int.48. 653-664 (1998)

[Publications] Hongyo,T.,et al.: "Frequent p53 mutation at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.58. 1105-1107 (1998)

[Publications] Kanno,H.,et al.: "Appearance of different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL." Leukemia. 12. 1288-1294 (1998)

[Publications] Kojya,S.,et al.: "Site spectic localization of Epstein-Barr virus in the pharyngeal carcinomas." Jpn.J.Cancer Res.89. 510-515 (1998)

[Publications] Tomita,Y.,et al.: "Plasmacytoma of the gastrointestinal tract in Korea : higher incidence rate than in Japan and EBV-association." Oncology. 55. 27-32 (1998)

[Publications] Yanai,H.,et al.: "Epstein-Barr virus infection of the colon with inflammatory bowel disease." Am.J.Gastroenterol.(in press).

[Publications] Yanai,H.,et al.: "The backgraound atrophic gastristis for Epstein-Barr virus-associated gastrc carcinoma." J.Clin.Gastroenterol. (in press).

[Publications] Tada-Oikawa,S.,et al.: "Generation of hydrogen peroxide precedes loss of mitochondrial membrane potential DNA alkylation-induced apoptosis." FEBS Letters. 442. 65-69 (1999)

[Publications] Yang,W-I.,et al.: "Epstein-Barr virus and gastrointestinal lymphomas in Korea." Yonsei.Med.J.39. 268-276 (1998)

[Publications] Sairenji,T.,et al.: "Immune responses to Epstin-Barr virus infection." In Herpes-Virus and Immunity (Medveczky et a1.,eds) Plenum Press.,NY,USA., (1998)

[Publications] Tokunaga,M.,et al.: "Epstein-Barr virus involvement in gaatric cancer : Biomarker for lymphnode metastnasis" Cancer Epidemiology,Biomarker & Prevention. (in press),

[Publications] Yanai,H.,et al.: "The gastric mucosa surrounding Epstein-Barr virus-associated gastric cancers." In″Gann Monograph on Cancer Research NO.45″ed.Osato T.Japan Scientific Societies Press,Tokyo pp., (1998)

西連寺剛鳥取大学, 医学部, 教授 (10117351)