Identification of risk factors of hepatocarcinogenesis in fatty liver disease through the comprehensive analysis of epigenetic alterations
Project/Area Number |
24590997
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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 |
Gastroenterology
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Research Institution | Kinki University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
HATANO Etsurou 京都大学, 大学院医学研究科, 准教授 (80359801)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 脂肪性肝疾患 / 肝細胞癌 / エピジェネティクス / がん抑制遺伝子 / 非アルコール性脂肪性肝疾患 / エピゲノム / DNAメチル化 / 脂肪肝 / 糖尿病 / 非アルコール性脂肪性肝炎 |
Outline of Final Research Achievements |
We found that oxidative DAN damage (8-OHdG) induced epigenetic alteration in HCC cell lines. In human chronic hepatitis C, number of methylated tumor suppressor genes (TSGs) was associated with time-to hepatocellular carcinoma (HCC) emergence. Through the comprehensive analysis of DNA methylation in virus-negative HCCs, methylation was affected by aging and presence of diabetes mellitus (DM), suggesting that age and DM might contribute to hepatocarcinogenesis through epigenetic mechanism. We analyzed risk factors of fatty liver-related HCC mergence using 8-OHdG level of hepatocyte as a surrogate marker, and found that serum AFP and hepatocyte ballooning were independently associated with 8-OHdG; number of methylated TSGs was significantly higher in livers with high degree of 8-OHdG levels in hepatocyte. These evidences support the idea that serum AFP level and hepatocyte ballooning could be a marker of high-risk group of HCC in patients with fatty liver.
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Heat shock protein A4/Apg-2 is required for stem/progenitor cell maintenance in intestinal inflammation.2015
Author(s)
Adachi T, Sakurai T, Kashida H, Mine H, Hagiwara S, Matsui S, Yoshida K, Nishida N, Watanabe T, Itoh K, Fujita J, Kudo M.
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Journal Title
Inflammatory Bowel Disease
Volume: 21
Issue: 1
Pages: 31-39
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison of systems for assessment of post-therapeutic response to sorafenib for hepatocellular carcinoma.2014
Author(s)
Arizumi T, Ueshima K, Takeda H, Osaki Y, Hayaishi S, Takita M, Inoue T, Kitai S, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M.
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Journal Title
J Gastroenterol.
Volume: 49
Issue: 12
Pages: 1578-1587
DOI
Related Report
Peer Reviewed
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[Journal Article] Genome-wide profiling of DNA methylation and tumor progression in human hepatocellular carcinoma.2014
Author(s)
Nishida N*, Nishimura T, Nakai T, Chishina H, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M.
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Journal Title
Dig Dis.
Volume: 32
Issue: 6
Pages: 658-663
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of the epigenetically inactivated genes in human hepatocellular carcinoma by integrative analyses of methylation profiling and pharmacological unmasking.2014
Author(s)
Nishida N, Chishina H, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M.
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Journal Title
Dig Dis.
Volume: 32
Issue: 6
Pages: 740-746
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Treatment response and tolerability in eldery patients with chronic hepatitis C: Subgroup analysis in ReGIT-J study.2014
Author(s)
Nishikawa H, Enomoto H, Saito M, Aizawa N, Tsuda Y, Higuchi K, Okazaki K, Seki T, Kim S-R, Hongo Y, Jyomura H, Nishida N, Kudo M, Osaki Y and Nishiguchi S.
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Journal Title
J Virol Antivir Res
Volume: 3
Issue: 02
Pages: 2-2
DOI
Related Report
Peer Reviewed
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[Journal Article] Radiofrequency Ablation for Hepatocellular Carcinoma Measuring 2 cm or Smaller: Results and Risk Factors for Local Recurrence.2014
Author(s)
Kono M, Inoue T, Kudo M, Chishina H, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Minami Y, Ueshima K, Nishida N, Murakami T.
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Journal Title
Dig Dis.
Volume: 32
Issue: 6
Pages: 670-677
DOI
Related Report
Peer Reviewed
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[Journal Article] Duration of stable disease is associated with overall survival in patients with advanced hepatocellular carcinoma treated with sorafenib.2014
Author(s)
Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M.
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Journal Title
Dig Dis.
Volume: 32
Issue: 6
Pages: 705-710
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Decreased blood flow after sorafenib administration is an imaging biomarker to predict overall survival in patients with advanced hepatocellular carcinoma.2014
Author(s)
Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M.
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Journal Title
Dig Dis.
Volume: 32
Issue: 6
Pages: 733-739
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Validation of the Criteria of Transcatheter Arterial Chemoembolization Failure or Refractoriness in Patients with Advanced Hepatocellular Carcinoma Proposed by the LCSGJ.2014
Author(s)
Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M.
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Journal Title
Oncology
Volume: 87
Issue: Suppl. 1
Pages: 32-36
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Combination Guidance of Contrast-Enhanced US and Fusion Imaging in Radiofrequency Ablation for Hepatocellular Carcinoma with Poor Conspicuity on Contrast-Enhanced US/Fusion Imaging.2014
Author(s)
Minami T, Minami Y, Chishina H, Arizumi T, Takita M, Kitai S, Yada N, Inoue T, Hagiwara S, Ueshima K, Nishida N, Kudo M.
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Journal Title
Oncology
Volume: 87
Issue: Suppl. 1
Pages: 55-62
DOI
Related Report
Peer Reviewed
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[Journal Article] Heat shock protein 27 expression is inversely correlated with atrophic gastritis and intraepithelial neoplasia.2013
Author(s)
Nagata Y, Kudo M, Nagai T, Watanabe T, Kawasaki M, Asakuma Y, Hagiwara S, Nishida N, Matsui S, Kashida H, Sakurai T
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Journal Title
Dig Dis Sci.
Volume: 58
Issue: 2
Pages: 381-388
DOI
Related Report
Peer Reviewed
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[Journal Article] Quantification of tumor DNA in serum and vascular invasion of human hepatocellular carcinoma.2013
Author(s)
Nishida N, Arizumi T, Takita M, Nagai T, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T et al
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Journal Title
Oncology
Volume: 84
Issue: Suppl. 1
Pages: 82-87
DOI
Related Report
Peer Reviewed
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[Journal Article] Impact of Combination Therapy with Peginterferon alpha-2b and Entecavir on Persistent Viral Suppression in Patients with Chronic Hepatitis B.2013
Author(s)
Hagiwara S, Kudo M, Osaki Y, Matsuo H, Inuzuka T, Matsumoto A, Tanaka E, Sakurai, Ueshima K, Inoue T, Yada N, Nishida N
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Journal Title
J Med Virol.
Volume: 85
Issue: 6
Pages: 987-995
DOI
Related Report
Peer Reviewed
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[Journal Article] Unique association between global DNA hypomethylation and chromosomal alterations in human hepatocellular carcinoma.2013
Author(s)
Nishida N, Kudo M, Nishimura T, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Yokomichi N, Nagasaka T, Goel A.
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Journal Title
PLoS One
Volume: 8
Issue: 9
Pages: e72312-e72312
DOI
Related Report
Peer Reviewed
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[Journal Article] Reactive Oxygen Species Induce Epigenetic Instability through the Formation of 8-Hydroxydeoxyguanosine in Human Hepatocarcinogenesis.2013
Author(s)
Nishida N, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M.
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Journal Title
Dig Dis.
Volume: 31
Issue: 5-6
Pages: 459-466
DOI
Related Report
Peer Reviewed
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[Journal Article] Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production.2013
Author(s)
Sakurai T, Kudo M, Watanabe T, Itoh K, Higashitsuji H, Arizumi T, Inoue T, Hagiwara S, Ueshima K, Nishida N, Fukumoto M, Fujita J.
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Journal Title
Dig Dis
Volume: 31
Issue: 5-6
Pages: 440-6
DOI
Related Report
Peer Reviewed
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[Journal Article] Risk of hepatocellular carcinoma development in cases of hepatitis C treated by long-term, low-dose PEG-IFNα-2a.2012
Author(s)
Nishida N, Arizumi T, Hayaishi S, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T,
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Journal Title
Dig Dis
Volume: 30
Issue: 6
Pages: 547-553
DOI
Related Report
Peer Reviewed
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[Presentation] Pathological feature, oxidative DNA damage and epigenetic alteration of tumor suppressor genes in non-alcoholic fatty liver disease.2014
Author(s)
Nishida N, Yada N, Arizumi T,Takita M, Kitai S, Inoue T, Hagiwara S,Minami Y, Sakurai T, Ueshima K, Kudo M
Organizer
65th Annual meeting of the American Association for the Study of Liver Diseases (AASLD).
Place of Presentation
Boston, MA, USA
Year and Date
2014-11-08 – 2014-11-11
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[Presentation] Serum microRNAs as diagnostic biomarkers for early colorectal neoplasms.2014
Author(s)
Yamada A, Horimatsu T, Okugawa Y, Nishida N, Kou T, Kusaka T, Honjo H, Amanuma Y, Kikuchi O, Muto M, Goel A, Boland CR.
Organizer
Annual meeting of the American Association for cancer research (AACR) 2014
Place of Presentation
San Diego, CA, USA
Year and Date
2014-04-05 – 2014-04-09
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