2007 Fiscal Year Final Research Report Summary
Identification and characterization of the genes responsible for the development of uterine cervical carcinoma : towards the molecular targetting.
| Project/Area Number |
18591832
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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 | Osaka University |
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Principal Investigator |
ENOMOTO Takayuki Osaka University, Graduate school of medinne, Associate Professor (90283754)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Masami Osaka University, Graduate school of medicine, Associate Professor (60303963)
MIYATAKE Takashi Osaka University, Graduate school of medicine, Assistant Professor (70448067)
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| Project Period (FY) |
2006 – 2007
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| Keywords | uterine cervical cancer / TSC403 / HB-EGF |
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| Research Abstract |
(1) Identification of pathways of cervical carcinogenesis
Cervical squamous cell carcinoma has been supposed to derive from reserve cells in squamo-columnar junction and develop stepwise through mild, moderate and severe dysplasia. Recent studies showed that type of HPV in severe dysplasia was different from that of mild dysplasia, implying that severe dysplasia does not necessarily develop through mild dysplasia. In our current study, we clarified that atypical immature metaplasia is formed by infection of malignant types of HPV, and that a new pathway from atypical immature metaplasia to severe dysplasia does exist.
Adenosquamous carcinoma occupies about 1% of the uterine cervical carcinomas. Adenocarcinoma- and squamous cell carcinoma-parts are concurrently detected in adenosquamous carcinoma, however, it has been still unclear whether those two parts are formed separately form different original cells or develop from a single origin differentiating two cell types. We demonstrated ade
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nosquamous carcinoma of the uterine cervix was demonstrated to be a combination tumor originating from a single Stem cell by clonality analysis.
(2) Identification of the genes regulating progression of cervical carcinoma
Thirty-two genes were identified as the genes responsible for development and progression of cervical carcinoma by DNA microarray analysis. Among them, Igfbp5 was shown to be significantly down-regulated from an early step of cervical carcinogenesis. Moreover, point mutation or amplification of PIK3CA gene was identified in 25% of cervical carcinoma cases. Inactivation of RUNX3 genes occurred in about 50% of uterine carcinoma. We also showed that B4-H7, a novel gene responsible for the development of ovarian cancer, plays a role in uterine carcinoma.
(3) Analysis of epithelial-stromal interaction of cervical carcinoma
We demonstrated, in vitro and in vivo, that HB-EGF secreted by the stroma of cervical carcinoma promotes proliferation of carcinoma cells by paracrine mechanism. Less
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[Journal Article] PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences2008
Author(s)
Miyake T, Yoshino K, Enomoto T, Takata T, Ugaki H, Kim A, Fujiwara K, Miyatake T, Fujita M, Kimura T
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Journal Title
Cancer Letters 8;261(1)
Pages: 120-126
Description
「研究成果報告書概要(和文)」より
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[Journal Article] PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences2008
Author(s)
Miyake, T, Yoshino, K, Enomoto, T, Takata, T, Ugaki, H, Kim, A, Fujiwara, K, Miyatake, T, Fujita, M, Kimura, T
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Journal Title
Cancer Letters 8, 261(1)
Pages: 120-126
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clonality Analysis and HPV Infection in Squamous Metaplasia and Atypical Immature Metaplasia of Uterine Cervix : Is Atypical Immature Metaplasia a Precursor to C1N 32007
Author(s)
Miyatake, T, Ueda, Y, Yoshini, K, Shroyer, K R, Kanao, H, Sun, H, Nakashima, R, Kimura, T, Wakasa, T, Enomoto, T
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Journal Title
International Jornal of Gynecological Pathology(IJGP) 26(2)
Pages: 180-187
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Down-regulation of insuline-like growth factor binding protein-5 (IGEBP-5) : novel maker for cervical carcinogenesis2007
Author(s)
Miyatake, T, Ueda, Y, Nakashima, R, Yoshino, K, Kimura, T, Murata, T, Nomura, T, Fujita, M, Buzard, G S, Enomoto, T
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Journal Title
International Journal of Cancer 120
Pages: 2068-2077
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] B7-H4(DD-0110) is overexpressed in high risk uterine Endometrioid adenocarcinoma and inversely correlated with tumor T-cell infiltration.2007
Author(s)
Miyatake, T, Tringler, B, Liu, W, LiuSH, Papkoff, J, Enomoto, T, Torkko, KC, Dehn, DL, Swisher, A, Shroyer, KR
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Journal Title
Gynecol Oncol 106(1)
Pages: 119-27
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinicopathological analysis of cervical cancer in young adults2007
Author(s)
Kirn, A, Takata, T, Ugaki, H, Fujiwara, K, Miyake, T, Miyatake, T, Yoshino, K, Fujita, M, Enomoto, T, Kimura, T
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Journal Title
Advances in Obstetrics and Gynecology Vol.59, No.2
Pages: 102-104
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] B7-H4 overexpression in ovarian tumors2006
Author(s)
Tringler, B, Liu, W, Corral, L, Torkko, K, C, Enomoto, T, Davidson, S, Lucia, M, S, Heinz, D, E, Papkoff, J, Shroyer, K, R
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Journal Title
Gynecologic Oncology 100
Pages: 44-52
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Frequent Inctivation of RUNX3 in Endometrial Carcinoma
Author(s)
Yoshizaki, T, Enomoto, T, Fujita, M, Ueda, Y, Miyatake, T, Fujiwara, Miyake, T, Kimura, T, Yoshino, K, Kimura, T
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Journal Title
Gynecologic Oncology (In press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clonality and HPV Infection Analysis of Concurrent Glandular-and Squamous Leions and Adenosquamous Carcinomas of the Uterine Cervix
Author(s)
Ueda, Y, Miyatake, T, Okazawa, M, Kimura, T, Miyake, T, Fujiwara, K, Yoshino, K, Nakashima, R, Fujita, hl, Enomoto, T
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Journal Title
American Jornal of Clinical Pathology (In press)
Description
「研究成果報告書概要(欧文)」より
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