The functional analyses and the therapeutic applications of a novel tumor suppressor gene ZNF395 involved in the progression of pancreatic cancers.
Project/Area Number |
17K08695
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Human pathology
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Research Institution | Oita University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
兒玉 雅明 大分大学, 福祉健康科学部, 教授 (20332893)
泥谷 直樹 大分大学, 医学部, 准教授 (80305036)
守山 正胤 大分大学, 医学部, 教授 (90239707)
沖本 忠義 大分大学, 医学部, 講師 (90381037)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 膵癌 / ZNF395 / がん抑制遺伝子 / 細胞周期 / 免疫組織化学 / 発現誘導 / 増殖能 / シグナルパスウェイ |
Outline of Final Research Achievements |
To elucidate the functional significance of downregulation of ZNF395 due to 8p loss in pancreatic carcinogenesis, pancreatic cancer cell lines for doxycycline-inducible expression of ZNF395 were established. The proliferation potentials were markedly suppressed through a cell cycle arrest by induction of ZNF395. Immunohistochemical analyses of resected pancreatic cancer tissues revealed that the expression of ZNF395 was observed in cytoplasm of non-tumorous pancreatic ducts and acinar glands. In addition, it was detectable in intraepithelial lesions. On the other hand, ZNF395 expression was significantly reduced in the cancer cells in invasive lesions, especially in these with poor differentiation. Downregulation of ZNF395 showed a tendency to be worse prognosis in the patients with pancreatic cancers.
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Academic Significance and Societal Importance of the Research Achievements |
膵前癌病変が浸潤癌へ進展する分子メカニズムの一部を明らかにした。8p欠失に伴うZNF395の発現低下は膵癌前駆細胞に細胞周期の脱制御と増殖能亢進をもたらした。今後、ZNF395の下流で活性化されるシグナルパスウェイの同定を目指す。本研究で得られる知見は、新規の膵癌早期診断法および分子標的治療法の開発に応用可能である。予後不良な難治癌である膵癌の治療成績の向上に寄与することを期待する
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] A transgenic mouse expressing miR-210 in proximal tubule cells shows mitochondrial alteration: possible association of miR-210 with a shift in energy metabolism.2020
Author(s)
Nakada C, Hijiya N, Tsukamoto Y, Yano S, Kai T, Uchida T, Kimoto M, Takahashi M, Daa T, Matsuura K, Shin T, Mimata H, Moriyama M.
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Journal Title
J Pathol.
Volume: in press
Issue: 1
Pages: 12-25
DOI
Related Report
Peer Reviewed
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[Journal Article] Differences in <i>Helicobacter pylori</i> and CagA antibody changes after eradication between subjects developing and not developing gastric cancer2019
Author(s)
Kodama M, Okimoto T, Mizukami K, Fukuda K, Ogawa R, Okamoto K, Matsunari O, Kawahara Y, Hirashita Y, Murakami K.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 65
Issue: 1
Pages: 71-75
DOI
NAID
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed / Open Access
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[Journal Article] Complete Sequences of the Human T-Cell Leukemia Virus Type 1 Proviral Genomes from Newly Established Adult T-Cell Leukemia Cell Lines in Oita Prefecture, Japan2018
Author(s)
Fukumoto T, Ikebe E, Ogata M, Kohno K, Kuramitsu M, Sato Y, Fife N, Matsumoto T, Yahiro T, Ikeda M, Kusano S, Okayama A, Hori M, Hijiya N, Tsukamoto Y, Hirashita Y, Moriyama M, Ahmed K, Hasegawa H, Nishizono A, Saito M, Iha H
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Journal Title
Genome Announcements
Volume: 6
Issue: 25
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of fibrotic remodeling and cytokines/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation2018
Author(s)
Abe I, Teshima Y, Kondo H, Kaku H, Kira S, Ikebe Y, Saito S, Fukui A, Shinohara T, Yufu K, Nakagawa M, Hijiya N, Moriyama M, Shimada T, Miyamoto S, Takahashi N
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Journal Title
Heart Rhythm
Volume: 15
Issue: 11
Pages: 1717-1727
DOI
Related Report
Peer Reviewed
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[Journal Article] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer2018
Author(s)
Saito T, Niida A, Uchi R, Hirata H, Kodama M, Okimoto T, Murakami K, Suzuki Y, Ogawa S, Miyano S, Mimori K, et al.
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 2884-2884
DOI
NAID
Related Report
Peer Reviewed / Open Access
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