Explore new therapies targeting endoplasmic reticulumn stress response for Hepatocellular Carcinoma
| Project/Area Number |
16K19346
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Zhang Yizhou 広島大学, 医歯薬保健学研究科(医), 研究員 (70711117)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝細胞癌 / 小胞体ストレス / BBF2H7 / 分子標的治療 / ER stress response / CRISPR-CAS9 / cancer targeted therapy / ゲノム編集 |
|---|
| Outline of Final Research Achievements |
Using genome-wide transcriptome profiles and in vitro validation, we elucidated the mechanism of how ER stress transducer CREB3L2/BBF2H7 promotes hepatocarcinogenesis. BBF2H7 is over-activated in hepatocellular carcinoma (HCC), and is associated with an aggressive HCC subtype correlating with poor clinical outcome. At the molecular level, we found a partial fragment of BBF2H7 to be competitively bound to a subunit of AP-1, thus blocking AP-1 transcriptional activity and indirectly suppressing the stability of p53. In rescue experiments, we demonstrated that this fragment is indispensable to the proliferation of HCC, suggesting a potential target for the treatment of this common cancer.
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Report
(3 results)
Research Products
(6 results)
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[Journal Article] Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy.2018
Author(s)
Masuda K, Ono A, Aikata H, Kawaoka T, Nelson Hayes C, Teraoka Y, Daijo K, Nakamura-Inagaki Y, Morio K, Fujino H, Kan H, Uchida T, Masaki K, Kobayashi T, Nakahara T, Makokha GN, Zhang Y, Nagaoki Y, Miki D, Tsuge M, Hiramatsu A, Imamura M, Abe-Chayama H, Kawakami Y, Ochi H, Chayama K.
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Journal Title
J Gastroenterol.
Volume: 53
Issue: 1
Pages: 107-118
DOI
Related Report
Peer Reviewed
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[Journal Article] The association between serum cytokine and chemokine levels and antiviral response by entecavir treatment in chronic hepatitis B patients2017
Author(s)
Kurihara M, Tsuge M, Murakami E, Mori N, Ohishi W, Uchida T, Fujino H, Nakahara T, Abe-Chayama H, Kawaoka T, Miki D, Hiramatsu A, Imamura M, Kawakami Y, Aikata H, Ochi H, Zhang Y, Makokha GN, Hayes CN, Chayama K.
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Journal Title
Antivir Ther
Volume: Epub ahead of print
Issue: 3
Pages: 239-248
DOI
Related Report
Peer Reviewed
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[Journal Article] Persistent loss of HBV markers in serum without cellular immunity by combination of PEG-IFN plus ETV therapy in humanized mice2017
Author(s)
Uchida T, Imamura M, Hayes CN, Hiraga N, Kan H, Tsuge M, Abe-Chayama H, Zhang Y, Makokha GN, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K
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Journal Title
Antimicrob Agents Chemother
Volume: 61
Issue: 9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.2016
Author(s)
Tsuge M, Hiraga N, Uchida T, Kan H, Miyaki E, Masaki K, Ono A, Nakahara T, Abe-Chayama H, Zhang Y, Naswa MG, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K.
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Journal Title
Journal of Gastroenterology
Volume: In press
Issue: 11
Pages: 1073-1080
DOI
Related Report
Peer Reviewed / Open Access
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