| Project/Area Number |
11670183
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Ibaraki Prefectural University of Health Sciences |
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Principal Investigator |
OGATA Takesaburo Ibaraki Prefectural University of Health Sciences, Department of Pathology, Professor, 保健医療学部, 教授 (60009115)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Hitoshi Ditto, Professor, 医学部, 教授 (20094302)
YAZAWA Takuya Yokohama City University School of Medicine, Department of Pathology, Lecturer, 医学部, 講師 (50251054)
HORIGUCHI Hisashi Ditto, Assistant, 保健医療学部, 助手 (30238795)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Neuroendocrine cancer / Class II Major Histocompatibility Complex / Class II transactivator / Promoter / L-Myc / N-Myc / Human Achaete-Scute Complex Homologue-1 / Tumor Immunity / MHC class II |
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| Research Abstract |
Small cell lung cancer (SCLC) and neuroblastoma (NB) are representatives of neuroendocrine cancers and of the most aggressive adult and pediatric neoplasms. Severe reduction of major histocompatibility complex (MHC) in SCLC and NB is considered as one of causes of their poor prognoses. We show here that neuroendocrine cancers have ingenious molecular mechanisms escaping from antitumor immunity. The MHC reduction is caused by insufficient interferon-gamma (IFN-γ) induction of class II transactivator (CIITA), the most important transcription factor for MHC, through binding of human achaete-scute complex homologue-1 (HASH-1), L-Myc, and N-Myc, which are frequently overexpressed in neuroendocrine cancers, to the E-box in the CIITA promoter IV.The HASH-1 expression is involved in overexpressed L-myc and N-myc and is up-regulated by the IFN-γ treatment, both phenomena resulting in accelerating CIITA repression. Neveztheless, the MHC in SCLC and NB is easily improved through the CIITA gene transfection, and our preliminary animal experiments showed that certain murine NB cells can generate significant antitumor immunity in syngeneic hosts through the CIITA-mediated MHC induction. These results strongly suggest that the CIITA gene transfection may be an essential weapon to establish effective antitumor immunotherapy against neuroendocrine cancers.
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