| Project/Area Number |
14207009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUKAYAMA Masashi The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70281293)
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| Co-Investigator(Kenkyū-buntansha) |
UOZAKI Hiroshi The University of Tokyo Hospital, Research Associate, 医学部附属病院, 助手 (10296246)
KASHIMA Takeshi The University of Tokyo, Graduate School of Medicine, Research Associate, 医学部附属病院, 助手 (70292729)
SHIBAHARA Junji The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60334380)
USHIKU Tetsuo The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60376415)
OHTA Yasunori The University of Tokyo Hospital, Research Associate, 医学部附属病院, 助手
鄭 子文 東京大学, 大学院・医学系研究科, 講師 (90285768)
山内 直子 東京大学, 医学部附属病院, 助手 (90311638)
竹内 賢吾 東京大学, 医学研附属病院, 助手 (40323612)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000)
Fiscal Year 2004: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2003: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2002: ¥31,200,000 (Direct Cost: ¥24,000,000、Indirect Cost: ¥7,200,000)
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| Keywords | EB virus / gastric carcinoma / pyothorax-associated lymphoma / interleukin 1-b / genetic polymorphism / methylation / promoter / AIDS lymphoma / EBウイルス関連腫瘍 / EBウイルス関連胃癌 / IL1-β / 胃癌細胞株 / アポトーシス / DNAチップ / 遺伝子発現プロファイル / SCIDマウス移植株 / プロモーター領域 |
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| Research Abstract |
EB virus-associated gastric carcinoma : Global m-RNA expression analysis of a strain of EB-virus associated gastric carcinoma, which is transplantable in SCID mice, has demonstrated that interleukin 1-β(IL1-β) was highly expressed among the cytokine-related genes, when compared to EB virus-negative strains. IL1-β mRNA signals were specifically observed by in situ hyridization in surgically resected cancer tissues of EB virus-associated gastric carcinoma. Next, IL1-β polymorphisms were evaluated in Japanese patients with gastric cancer. Certain polymorphism was at high risk for EB virus-negative gastric carcinoma, but not for EB virus-positive one. Thus, IL1-β may be directly associated with the maintenance of EB virus-associated gastric carcinoma, and it may be also related with the development of EB virus-negative gastric carcinoma through its polymorphism.
Promoter methylation of various cancer-related genes was evaluated by methylation specific PCR. As a result, EB virus-associated gastric carcinoma showed global and non-random, and immunohistochemical expression of p16 and E-cadherin in cancer tissues was decreased or abnormal along with methylation of each corresponding promoter. When the methylation profile of p14 promoter was evaluated by the Bisulfite sequencing, high density methylation was observed in all of 29 CpG sites in contrast to low density and infrequent methylation in EB virus-negative gastric carcinoma. Since expression of DNMT1, 3a and 3b was not different between gastric carcinomas with or without infection of EB virus, there might be a mechanism specific to EB virus infection of stomach epithelial cells.
Pyotherax associated lymphoma : Pyothorax-associated lymphoma shows Latency III of EB virus infection similar to AIDS lymphomas. The DNA chip analysis of both Latency III type lymphomas demonstrated that five genes were characteristic to pyothorax-associated lymphoma, that is, PRAD,CEB1,GFOD,INSR (insulin receptor, X02160), MGC23980 (C9orf72).
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