Study on a novel mechanism of gemcitabine resistance
Project/Area Number |
17K15648
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Human pathology
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Research Institution | Nara Medical University |
Principal Investigator |
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Research Collaborator |
KUNIYASU Hiroki
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 膵管癌 / ゲムシタビン / 薬剤耐性 / MAST4 / AKT / 酸化ストレス / AKT3 / 膵癌 / 抗癌剤耐性 / 薬剤耐性機構 / 抗癌剤増感 |
Outline of Final Research Achievements |
In the gemcitabine resistant strain MIA-PaCa2-GEM, MAST4 expression was enhanced compared to the parent strain MIA-PaCa2. MAST4 expression has been correlated with cancer progression, poor prognosis, and gemcitabine resistance in human pancreatic ductal carcinoma. When MAST4 was knocked down in MIA-PaCa2-GEM, gemcitabine resistance disappeared. MAST4 interacts with AKT3 in the nucleus, and it is thought that AKT3 activation induces gemcitabine resistance via the AKT3-target genes, such as FoxO3. Moreover, it was thought that MAST4 upregulation was induced by miR 582-5p downregulation. MAST4 is a novel gemcitabine resistance gene in pancreatic ductal cancer and a prognostic factor, and is expected as a novel molecular target in pancreatic ductal cancer.
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Academic Significance and Societal Importance of the Research Achievements |
膵管癌は、早期診断・早期治療が困難で生物学的悪性度も高く、最も悪性度の高い難治癌である。治療困難の要因の一つが有効な抗がん剤の少なさと耐性獲得による抗がん剤の無力化である。ゲムシタビンは膵管癌に有効性な数少ない抗がん剤の一つであるが、多くの症例では投与中に耐性を生じ効果が失われる。本研究ではゲムシタビン耐性を解除する新たな分子標的を見出すことに成功しており膵管癌の治療の改善につながると期待される。
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Targeting claudin-4 enhances CDDP-chemosensitivity of gastric cancer2019
Author(s)
Nishiguchi Y, Fujiwara-Tani R, Sasaki T, Luo Y, Ohmori H, Kishi S, Mori S, Goto K, Yasui W, Sho M*, Kuniyasu H
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Journal Title
Oncotarget
Volume: 10
Issue: 22
Pages: 2189-2202
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy2019
Author(s)
Fujiwara-Tani R, Sasaki T, Ohmori H, Luo Y, Goto K, Nishiguchi Y, Mori S, Nakashima C, Mori T, Miyagawa Y, Kawahara I, Fujii K, Kishi S, Tatsumoto N, Kuniyasu H
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Journal Title
Pathobiology
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Magnetic hyperthermia using self-controlled heating elements consisting of Fe-Al milling alloy induces cancer cell apoptosis while preserving skeletal muscle.2019
Author(s)
Kawahara I, Goto K, Kodama K, Luo Y, Fujiwara-Tani R, Mori T, Miyagawa Y, Tanaka H, Kodama H, Hirayama A, Hosoito N, Taniguchi Y, Miki Y, Kuniyasu H
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Journal Title
Pathobiology
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Intermittent calorie restriction enhances epithelial- mesenchymal transition through alteration of energy metabolism in a mouse tumor model.2018
Author(s)
Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H
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Journal Title
Int J Oncol
Volume: 52
Pages: 413-423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma2018
Author(s)
Nakashima C, Yamamoto K, Fujiwara-Tani R, Luo Y, Matsushima S, Fujii K, Ohmori H, Sasahira T, Sasaki T, Kitadai Y, Kirita T, Kuniyasu H
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Journal Title
Cancer Sci
Volume: in press
Issue: 6
Pages: 2036-2045
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pro-metastatic signaling of elaidic acid, a trans fatty acid, is associated with lipid rafts.2018
Author(s)
Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Nakashima C, Sasaki T, Kuniyasu H
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Journal Title
Oncol Lett
Volume: 15
Pages: 4423-4426
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pro-metastatic intracellular signaling of elaidic acid, a trans fatty acid.2017
Author(s)
Fujii K, Luo Y, Nishiguchi Y, Fujiwara R, Kishi S, He S, Yang S, Sasaki T, Ohmori H, Kuniyasu H
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Journal Title
Int J Oncol
Volume: 50
Issue: 1
Pages: 85-92
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Elaidic acid, a trans fatty acid, enhances the metastasis of colorectal cancer cells2017
Author(s)
Ohmori H, Fujii K, Kadochi Y, Mori S, Nishiguchi Y, Fujiwara R, Kishi S, Sasaki T, Kuniyasu H
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Journal Title
Pathobiol
Volume: in press
Issue: 3
Pages: 144-151
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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