2011 Fiscal Year Final Research Report
For development of a new therapeutic approach : Examination of biological response of uterine leiomyosarcoma in microenvironments
| Project/Area Number |
21592126
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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 |
Obstetrics and gynecology
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| Research Institution | Shinshu University |
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Principal Investigator |
HAYASHI Takuma 信州大学, 医学系研究科, 准教授 (60359726)
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| Co-Investigator(Renkei-kenkyūsha) |
KONISHI Ikuo 京都大学, 大学院・医学系研究科, 教授 (90192062)
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| Project Period (FY) |
2009 – 2011
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| Keywords | LMP2 / 子宮平滑筋肉腫 / 血行性転移 / 老化 |
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| Research Abstract |
Hayashi et al. reported that defective LMP2 expression is likely to be one of the risk factors in the development of human uterine LMS as it is in LMP2-deficient mice. The importance of the IFN-γpathway in the transcriptional regulation of the LMP2 promoter has been established in another study, where defective LMP2 expression was attributable to mutations in the catalytic region of JAK1 in a human uterine LMS SKN cell line.
In the present study, we investigated whether LMP2 expression was markedly down-regulated in human uterine LMS tissues in comparison with both LMA and normal myometrium. Biological and histological findings showed that defective LMP2 expression contributed to abnormal cell proliferation, which directly correlated to tumor progression. Disruption of LMP2 expression stemmed from defects in the IFN-γsignaling pathway, specifically from somatic mutations in JAK1. Furthermore, LMP2 expression appeared to be responsible for the suppression of specific transformed phenotypes of human uterine LMS cells in an anti-oncogenic manner. Continued improvement of our knowledge of the molecular biology of uterine LMS may ultimately lead to novel diagnoses and therapies and improved outcome.
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[Journal Article] Tumor Immunoediting from T cell-Mediated Immune Surveillance to Tumor-Escape of Uterine Laiomyosarcoma2012
Author(s)
Hayashi T, Horiuchi A, Sano K, HiraokaN, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
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Journal Title
J Vaccines Vacci
Volume: S1
Pages: 1-6
Peer Reviewed
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[Journal Article] Tumor immunoediting ; from immunosurveillance to tumor-escape on uterine leiomyosarcma2011
Author(s)
Hayashi T, Horiuchi A, Sano K, HiraokaN, Kasai M, Ichimura T, Nagase S, IshikoO, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
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Journal Title
Current Res. Cancer
Volume: 4
Pages: 36-45
Peer Reviewed
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[Journal Article] Involvement of proteasomeβ1i subunit, LMP2, on development of uterine leiomyosarcma2011
Author(s)
Hayashi T, Horiuchi A, Sano K, HiraokaN, Kasai M, Ichimura T, Nagase S, IshikoO, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
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Journal Title
North Ame J Med Sci
Volume: 3
Pages: 394-399
Peer Reviewed
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[Journal Article] Involvement of LMP2, IFN-γ-inducible factor, on development of uterine leiomyosarcma2011
Author(s)
Hayashi T, Horiuchi A, Sano K, HiraokaN, Kasai M, Ichimura T, Nagase S, IshikoO, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
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Journal Title
Current Res. Immunol
Volume: 5
Pages: 51-63
Peer Reviewed
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