1998 年度実績報告書

EBウイルスとヒト発がん

研究課題

研究課題/領域番号	09253103
研究種目	特定領域研究(A)
研究機関	鳥取大学
研究代表者	西連寺剛鳥取大学, 医学部, 教授 (10117351)
研究分担者	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)
キーワード	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
研究概要	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。

研究成果

(31件)

すべてその他

すべて文献書誌 (31件)

[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Hirai,K.,et al.: "Epstein-Barr virus genome in infected cel1s and cancer." Gann Monograph on Cancer Res.45. 29-39 (1998)
[文献書誌] Shirakata,M.,et al.: "Identification of minimal oriP of Epstein-Barr virus required for DNA replication." J.Biochem.123. 175-181 (1998)
[文献書誌] 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)
[文献書誌] 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).
[文献書誌] 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)
[文献書誌] 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).
[文献書誌] Murakami,K.,et al.: "A case of large vessel arteritis associated with chronic active Esptein-Barr virus infection." Arth.Rheum.41. 369-373 (1998)
[文献書誌] 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)
[文献書誌] Hogyo,T.,et al.: "Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.(in press).
[文献書誌] Ohsawa,M.,et al.: "Rick of non-Hodgkin′s lymphoma in patients with hepatitis C virus infection." Int.J.Cancer.(in press).
[文献書誌] 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)
[文献書誌] Fukayama,M.,et al.: "Epstein-Barr virus and gastric carcinoma." Gastic Cancer (in press).
[文献書誌] Nishiwaki,J.,et al.: "Hypoechoic submucosal nodules ; A sign of Epstein-Barr virus-associated early gastric cancer." J.Gastroenterol Hepatol.13. 585-590 (1998)
[文献書誌] Ohsawa,M.,et al.: "Characteristics of non-Hodgkin's lymphoma complicnted with renal cell malignancies." Oncogene. 55. 482-486 (1998)
[文献書誌] Kanno,H.,et al.: "Mechanisms for the development of pyothorax-associated lymphoma." Pathol.Int.48. 653-664 (1998)
[文献書誌] Hongyo,T.,et al.: "Frequent p53 mutation at dipyrimidine sites in patients with pyothorax-associated lymphoma (PAL)." Cancer Res.58. 1105-1107 (1998)
[文献書誌] 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)
[文献書誌] Kojya,S.,et al.: "Site spectic localization of Epstein-Barr virus in the pharyngeal carcinomas." Jpn.J.Cancer Res.89. 510-515 (1998)
[文献書誌] 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)
[文献書誌] Yanai,H.,et al.: "Epstein-Barr virus infection of the colon with inflammatory bowel disease." Am.J.Gastroenterol.(in press).
[文献書誌] Yanai,H.,et al.: "The backgraound atrophic gastristis for Epstein-Barr virus-associated gastrc carcinoma." J.Clin.Gastroenterol. (in press).
[文献書誌] 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)
[文献書誌] Yang,W-I.,et al.: "Epstein-Barr virus and gastrointestinal lymphomas in Korea." Yonsei.Med.J.39. 268-276 (1998)
[文献書誌] 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)
[文献書誌] Tokunaga,M.,et al.: "Epstein-Barr virus involvement in gaatric cancer : Biomarker for lymphnode metastnasis" Cancer Epidemiology,Biomarker & Prevention. (in press),
[文献書誌] 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 年度 実績報告書

EBウイルスとヒト発がん

研究代表者

西連寺 剛 鳥取大学, 医学部, 教授 (10117351)

研究成果

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

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

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

[文献書誌] 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)

[文献書誌] 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).

[文献書誌] 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)

[文献書誌] 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).

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

[文献書誌] 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)

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

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

[文献書誌] 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)

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

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

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

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

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

[文献書誌] 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)

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

[文献書誌] 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)

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

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

[文献書誌] 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)

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

[文献書誌] 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)

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

[文献書誌] 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 年度実績報告書

西連寺剛鳥取大学, 医学部, 教授 (10117351)