2013 Fiscal Year Final Research Report
Development of a new therapeutic tool against malignant mesothelioma
| Project/Area Number |
24650650
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Clinical oncology
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| Research Institution | 愛知県がんセンター(研究所) |
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Principal Investigator |
SEKIDO Yoshitaka 愛知県がんセンター(研究所), 分子腫瘍学部, 副所長 兼 部長 (00311712)
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| Co-Investigator(Kenkyū-buntansha) |
近藤 英作 愛知県がんセンター(研究所), 腫瘍病理学部, 部長 (30252951)
藤井 万紀子 愛知県がんセンター(研究所), 分子腫瘍学部, 主任研究員 (70406031)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 分子標的治療 / 悪性中皮腫 / ペプチド創薬 |
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| Research Abstract |
Malignant mesothelioma (MM) is a very aggressive tumor and, currently, there are no effective chemotherapeutic drugs or molecular-target reagents against this fatal disease. In this project, we performed experiments to develop a new therapeutic modality against MM. Since MM shows frequent inactivation of p16INK4a tumor suppressor gene, we employed a functional peptide which is permeable through the cell membrane and restores p16 function. We found that this peptide induced apoptosis of MM cells very effectively and specifically, which seemed promising to be a new therapeutic tool. Furthermore, we also analyzed YAP oncogene product, which is constitutively activated and leads to more malignant phenotypes of MM cells. We clarified which members of TEAD family transcription factors, YAP binding partners, were important in deregulated MM cell proliferation. These findings were very indicative to develop a new strategy to regulate YAP protein as a therapeutic modality of MM.
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Research Products
(33 results)
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[Journal Article] Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production2014
Author(s)
Chew S-H, Okazaki Y, Nagai H, Misawa N, Akatsuka S, Yamashita K, Jiang L, Yamashita Y, Noguchi M, Hosoda K, Sekido Y, Takahashi T, Toyokuni S
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Journal Title
Carcinogenesis
Volume: 35
Pages: 164-72
Peer Reviewed
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[Journal Article] A novel targeting therapy of malignant mesothelioma using anti-podoplanin antibody2013
Author(s)
Abe S, Morita Y, Kato-Kaneko M, Hanibuchi M, Tsujimoto Y, Goto H, Kakiuchi S, Aono Y, Huang J, Sato S, Kishuku M, Taniguchi Y, Azuma M, Kawazoe K, Sekido Y, Yano S, Akiyama S, Sone S, Minakuchi K, Kato Y, Nishioka Y
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Journal Title
J Immunol
Volume: 190
Pages: 6239-40
Peer Reviewed
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[Journal Article] YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle promoting genes2012
Author(s)
Mizuno T, Murakami H, Fujii M, Ishiguro F, Tanaka I, Kondo Y, Akatsuka S, Toyokuni S, Yokoi K, Osada H, Sekido Y
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Journal Title
Oncogene
Volume: 31
Pages: 5117-22
Peer Reviewed
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[Journal Article] TGF-beta synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth2012
Author(s)
Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H, Sekido Y
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Journal Title
J Exp Med
Volume: 209
Pages: 479-94
Peer Reviewed
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[Journal Article] Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells2012
Author(s)
Horio M, Sato M, Takeyama Y, Elshazley M, Yamashita R, Hase T, Yoshida K, Usami N, Yokoi K, Sekido Y, Kondo M, Toyokuni S, Gazdar AF, Minna JD, Hasegawa Y
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Journal Title
Ann Surg Oncol
Volume: 19 Suppl 3
Pages: S634-45
Peer Reviewed
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[Journal Article] The circadian clock gene BMAL1 is a novel therapeutic target for malignant mesothelioma2012
Author(s)
Elshazley M, Sato M, Hase T, Yamashita R, Yoshida K, Toyokuni S, Ishiguro F, Osada H, Sekido Y, Yokoi K, Usami N, Shames DS, Kondo M, Gazdar AF, Minna JD, Hasegawa Y
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Journal Title
Int J Cancer
Volume: 13
Pages: 2820-31
Peer Reviewed
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[Journal Article] Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems2012
Author(s)
Kondo E, Saito K, Tashiro Y, Kamide K, Uno S, Furuya T, Mashita M, Nakajima K, Tsumuraya T, Kobayashi N, Nishibori M, Tanimoto M, Matsushita M
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Journal Title
Nature Commun
Volume: 3
Pages: 951-963
Peer Reviewed
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[Journal Article] LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade
Author(s)
Tanaka I, Osada H, Fujii M, Fukatsu A, Hida T, Horio Y, Kondo Y, Sato A, Hasegawa Y, Tsujimura T, Sekido Y
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Journal Title
Oncogene
Volume: (in press)
Peer Reviewed
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