Evolution of ovarian carcinoma cells through peritoneal dissemination ; genome-wide analysis and clinical application.
Project/Area Number |
21390452
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Kyoto University |
Principal Investigator |
KONISHI Ikuo 京都大学, 医学研究科, 教授 (90192062)
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Co-Investigator(Kenkyū-buntansha) |
MANDAI Masaki 京都大学, 医学研究科, 講師 (80283597)
MATSUMURA Noriomi 京都大学, 医学研究科, 助教 (20452336)
SUZUKI Ayako 京都大学, 医学研究科, 助教 (90378696)
BABA Tsukasa 京都大学, 医学研究科, 助教 (60508240)
八木 治彦 京都大学, 医学研究科, 助教 (70402857)
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Project Period (FY) |
2009 – 2011
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Project Status |
Completed (Fiscal Year 2011)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | 婦人科腫瘍学 / 卵巣癌 / 播種性転移 / 腫瘍免疫 / TGF-beta経路 / エピジェネティクス / TGFβ / マイクロアレイ / メチル化 / 低分子化合物 |
Research Abstract |
1) Treatment of 39 ovarian cancer cell lines and 17 primary culture samples with the inhibitor of DNA methylation, followed by expression microarray, identified genes targeted by DNA methylation in ovarian cancer. This analysis revealed TGF-beta signaling pathway is regulated by genome-wide DNA methylation. 2) We found TGF-beta pathway activity is upregulated in the omental metastases of ovarian cancer. Then we demonstrated the inhibitor of TGF-beta signaling pathway is effective against disseminated metastasis of ovarian cancer using a mouse model. 3) We found expression of PDL-1 in ovarian cancer cells suppresses activity of CD8 positive T lymphocytes, causes immune escape, and facilitates peritoneal dissemination of ovarian cancer.
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer2012
Author(s)
Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I.
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Journal Title
Int J Cancer
Volume: 130(1)
Issue: 1
Pages: 20-8
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Peer Reviewed
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[Journal Article] Preoperative differential diagnosis of minimal deviation adenocarcinoma and lobular end cervical glandular hyperplasia of the uterine cervix : a multicenter study of clinico pathology and magnetic resonance imaging findings2011
Author(s)
Takatsu A, Shiozawa T, Miyamoto T, Kurosawa K, Kashima H, Yamada T, Kaku T, Mikami Y, Kiyokawa T, Tsuda H, Ishii K, Togashi K, Koyama T, Fujinaga Y, Kadoya M, Hashi A, Susumu N, Konishi I.
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Journal Title
Int J Gynecol Cancer
Volume: 21(7)
Pages: 1287-96
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[Journal Article] Japan Society of Obstetrics and Gynecology ; Japan Association of Obstetricians and Gynecologists. Guidelines for obstetrical practice in Japan : Japan Society of Obstetrics and Gynecology(JSOG) and Japan Association of Obstetricians and Gynecologists(JAO2011
Author(s)
Minakami H, Hiramatsu Y, Koresawa M, Fujii T, Hamada H, Iitsuka Y, Ikeda T, Ishikawa H, Ishimoto H, Itoh H, Kanayama N, Kasuga Y, Kawabata M, Konishi I, Matsubara S, Matsuda H, Murakoshi T, Ohkuchi A, Okai T, Saito S, Sakai M, Satoh S, Sekizawa A, Suzuki
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Journal Title
J Obstet Gynaecol Res
Volume: 37(9)
Issue: 9
Pages: 1174-97
DOI
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Peer Reviewed
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[Journal Article] Involvement of proteasomeβ1i subunit, LMP2, on development of uterin leiomyosarcma2011
Author(s)
Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Shiozawa T, Kanai Y, Yaegashi N, Aburatani H, Tonegawa S, Konishi I.
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Journal Title
N Am J Med Sci
Volume: 3(9)
Pages: 394-9
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[Journal Article] Clinical value of FDG-PET for preoperative evaluation of endometrial cancer2011
Author(s)
Suga T, Nakamoto Y, Saga T, Higashi T, Hamanaka Y, Tatsumi M, Hayashida K, Hara T, Konishi I, Fujii S, Togashi K.
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Journal Title
Ann Nucl Med
Volume: 25(4)
Issue: 4
Pages: 269-75
DOI
NAID
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Peer Reviewed
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[Journal Article] GPR54 is a target for suppression of metastasis in endometrial cancer2011
Author(s)
Kang HS, Baba T, Mandai M, Matsumura N, Hamanishi J, Kharma B, Kondoh E, Yoshioka Y, Oishi S, Fujii N, Murphy SK, Konishi I.
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Journal Title
Mol Cancer Ther
Volume: 10(4)
Issue: 4
Pages: 580-90
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Peer Reviewed
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[Journal Article] Distinguishing primary from secondary mucinous ovarian tumors : an algorithm using the novel marker DPEP12011
Author(s)
Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I.
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Journal Title
Mod Pathol
Volume: 24(2)
Issue: 2
Pages: 267-76
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[Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy2011
Author(s)
Hayashi, T, A.Horiuchi, K.Sano, N.Hiraoka, M.Kasai, T.Ichimura, T.Sudo, Y.Tagawa, R.Nishimura, Ol Ishiko, Y.Kanai, N.Yaegashi, H.Aburatani, T.Shiozawa, I.Konishi
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Journal Title
Sci Rep
Volume: 1
Issue: 1
Pages: 180-180
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[Journal Article] Distinguishing primary from secondary mucinous ovariantumors : an algorithm using the novel marker DPEP1.2011
Author(s)
Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I.
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Journal Title
Modern Pathology
Volume: 24
Pages: 267-276
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[Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation.2011
Author(s)
Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I.
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Journal Title
American Journal of Surgical Pathology
Volume: 34
Pages: 1842-1848
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Peer Reviewed
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[Journal Article] GPR54 Is a Target for Suppression of Metastasis in Endometrial Cancer.2011
Author(s)
Kang HS, Baba T, Mandai M, Matsumura N, Hamanishi J, Kharma B, Kondoh E, Yoshioka Y, Oishi S, Fujii N, Murphy SK, Konishi I.
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Journal Title
Molecular Cancer Therapeutics
Volume: 10
Pages: 580-590
Related Report
Peer Reviewed
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[Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.2011
Author(s)
Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I.
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Journal Title
International Journal of Cancer
Related Report
Peer Reviewed
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[Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation2010
Author(s)
Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I.
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Journal Title
Am J Surg Pathol
Volume: 34(12)
Issue: 12
Pages: 1842-8
DOI
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Peer Reviewed
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[Journal Article] Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcripto me profiling2010
Author(s)
Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, Baba T, Hamanishi J, Kang HS, Matsui S, Mori S, Murphy SK, Konishi I.
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Journal Title
Cancer Sci
Volume: 101(12)
Issue: 12
Pages: 2658-63
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[Journal Article] Targeting slow-proliferating ovarian cancer cells2010
Author(s)
Kondoh E, Mori S, Yamaguchi K, Baba T, Matsumura N, Cory Barnett J, Whitaker RS, Konishi I, Fujii S, Berchuck A, Murphy SK.
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Journal Title
Int J Cancer
Volume: 126(10)
Issue: 10
Pages: 2448-56
DOI
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[Journal Article] Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer : a proposal for patient selection2010
Author(s)
Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko O, Kodama S, Yamaguchi S, Ochiai K, Takano M, Yokota H, Kawakami Y, Nishimura S, Ogishima D, Nakagawa S, Kobayashi H, Shiozawa T, Nakanishi T, Kamura T, Konishi I, Yoshikawa H.
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Journal Title
J Clin Oncol
Volume: 28(10)
Issue: 10
Pages: 1727-32
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[Journal Article] Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling.2010
Author(s)
Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, Baba T, Hamanishi J, Kang HS, Matsui S, Mori S, Murphy SK, Konishi I.
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Journal Title
Cancer Science
Volume: 101
Pages: 2658-2663
NAID
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[Journal Article] Targeting slow-proliferating ovarian cancer cells2010
Author(s)
Kondoh E, Mori S, Yamaguchi K, Baba T, Matsumura N, Cory Barnett J, Whitaker RS, Konishi I, Fujii S, Berchuck A, Murphy SK.
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Journal Title
Int J Cancer. 126
Pages: 2448-2456
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[Journal Article] Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma : the important role of Snail in ovarian tumori genesis and progression2009
Author(s)
Yoshida J, Horiuchi A, Kikuchi N, Hayashi A, Osada R, Ohira S, Shiozawa T, Konishi I.
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Journal Title
Med Mol Morphol
Volume: 42(2)
Issue: 2
Pages: 82-91
DOI
NAID
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