New strategy of treatment for ovarian cancer aiming intraperitoneal cell-cell communication induced by microenvironmental EMT
Project/Area Number |
25293341
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Nagoya University |
Principal Investigator |
Kikkawa Fumitaka 名古屋大学, 医学(系)研究科(研究院), 教授 (40224985)
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Co-Investigator(Kenkyū-buntansha) |
SHIBATA Kiyosumi 名古屋大学, 大学医学系研究科, 准教授 (90335026)
KAJIYAMA Hiroaki 名古屋大学, 大学医学系研究科, 准教授 (00345886)
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Co-Investigator(Renkei-kenkyūsha) |
SENGA Takeshi 名古屋大学, 大学医学系研究科, 准教授 (80419431)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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Keywords | 卵巣癌 / 腹膜播種 / 腹膜中皮細胞 / 細胞コミュニケーション / 上皮間葉転換 / 癌関連中皮細胞 / 中皮細胞 / TGF-ベータ / 転移・浸潤 |
Outline of Final Research Achievements |
The TGF-beta;-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells (OC). We show that TGF-beta;-stimulated human primary mesothelial cells (HPMCs) are able to promote cancer cell attachment and proliferation and the activation of the promoter activities of MMP-2 and MMP-9, which are metalloproteinases necessary for tumor invasion. Expression of the miR-200 family was down-regulated in HPMCs by TGF-beta; stimulation, and restoration of the expression of miR-200 family members in HPMCs suppressed cancer cell attachment and proliferation. Down-regulation of the miR-200 family by TGF-beta; induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs. Finally, we demonstrated that the delivery of the miR-200s to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells.2016
Author(s)
Yoshikawa N, Kajiyama H, Nakamura K, Utsumi F, Niimi K, Mitsui H, Sekiya R, Suzuki S, Shibata K, Callen D, Kikkawa F.
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Journal Title
Oncol Rep
Volume: 35(5)
Issue: 5
Pages: 2543-52
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The prognostic impact of pulmonary metastasectomy in recurrent gynecologic cancers: a retrospective single-institution study.2015
Author(s)
Adachi M, Mizuno M, Mitsui H, Kajiyama H, Suzuki S, Sekiya R, Utsumi F, Shibata K, Taniguchi T, Kawaguchi K, Yokoi K, Kikkawa F.
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Journal Title
Nagoya J Med Sci
Volume: 77
Pages: 363-72
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oncologic Outcome after Recurrence in Patients with Stage I Epithelial Ovarian Cancer: ~Are Clear-cell and Mucinous Histological Types a Different Entities?2014
Author(s)
Kajiyama H, Mizuno M, Shibata K, Umezu T, Suzuki S, Yamamoto E, Mitsui H, Sekiya, R, Niimi K, Kawai M, Nagasaka T, Kikkawa F.
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Journal Title
Eur J Obstet Gynecol Reprod Biol.
Volume: 181
Pages: 305-10
DOI
Related Report
Peer Reviewed
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[Journal Article] PLAGL2 regulates actin cytoskeletal architecture and cell migration.2014
Author(s)
Sekiya R, Maeda M, Yuan H, Asano E, Hyodo T, Hasegawa H, Ito S, Shibata K, Hamaguchi M, Kikkawa F, Kajiyama H, Senga T.
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Journal Title
Carcinogenesis
Volume: 35
Issue: 9
Pages: 1993-2001
DOI
Related Report
Peer Reviewed
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[Journal Article] PLAGL2 regulates actin cytoskeletalarchitecture and cell migration.2014
Author(s)
Sekiya R, Maeda M, Yuan H, Asano E, Hyodo T, Hasegawa H, Ito S, Shibata K,Hamaguchi M, Kikkawa F, Kajiyama H, Senga T
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Journal Title
Carcinogenesis
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells.2014
Author(s)
Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.
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Journal Title
Cancer Sci.
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology.2014
Author(s)
Kajiyama H, Shibata K, Mizuno M, Umezu T, Suzuki S, Sekiya R, Niimi K, Mitsui H, Yamamoto E, Kawai M, Nagasaka T, Kikkawa F.
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Journal Title
J Gynecol Oncol.
Volume: 25
Issue: 1
Pages: 43-50
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation2014
Author(s)
Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S
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Journal Title
Int J Cancer
Volume: 135
Issue: 2
Pages: 308-318
DOI
Related Report
Peer Reviewed
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