Novel epigenetic change by histone lysine carboxymethylation

• Project/Area Number: 24590450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: Fujii Kiyomu 奈良県立医科大学, 医学部, 研究員 (60284189)
• Co-Investigator(Kenkyū-buntansha): KUNIYASU Hiroki 奈良県立医科大学, 医学部, 教授 (00253055) ; CHIHARA Yoshitomo 奈良県立医科大学, 医学部, 講師 (40405395)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖尿病 / リジン・カルボキシメチル化 / ヒストン・アセチル化 / DNAメチル化 / 糖化 / 糖化最終産物 / ヒストン / 遺伝子発現 / リジンカルボキシメチル化 / H3ヒストンK27 / トリメチル化 / ヒストン・リジン修飾 / カルボキシメチル化 / エピジェネティクス / p16 / H4ヒストン / リジン残基 / アセチル化ヒストン

Outline of Final Research Achievements

The influence of histone lysine carboxymethylation (HL-CM), which is occurred in diabetic condition, was examined by detection of HL-CM to be compared with histone acetylation, the promoter DNA methylation and p16 gene expression. The hyperglycemic-oxidative conditions associated with diabetes mellitus induced HL-CM, which was considered to affect histone acetylation. Metformin showed the possibility of preventing gene silencing by HL-the CM.

Research Products

• [Journal Article] High motility group box 1 induces cancer aggressiveness and drug resistance. (2015)
  • Author(s): Ohmori H, Luo Y, Fujii K, Sasaki T, Kuniyasu H
  • Journal Title: Ann Clin Pathol Volume: 3 Pages: 1042-1042
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of the plasma free amino acids profiles in cancer patients is associated with dysregulated metabolism in skeletal muscle (2015)
  • Author(s): Luo Y, Yoneda J, Sasaki T, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Arch Cancer Res Volume: 3 Pages: 5-5
  • Peer Reviewed / Open Access
• [Journal Article] Expression of MAS1 in breast cancer. (2015)
  • Author(s): Luo Y, Tanabe E, Kitayoshi M, Nishiguchi Y, Fujiwara R, Matsushima S, Sasaki T, Sasahira T, Chihara Y, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Cancer Sci Volume: 106 Issue: 9 Pages: 1240-1248
  • DOI: 10.1111/cas.12719
  • Peer Reviewed / Open Access
• [Journal Article] Cancer therapeutic effects of titanium dioxide nanoparticles are associated with oxidative stress and cytokine induction (2015)
  • Author(s): Fujiwara R, Luo Y, Sasaki T, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Pathobiol Volume: 82 Issue: 6 Pages: 243-251
  • DOI: 10.1159/000439404
  • Peer Reviewed
• [Journal Article] Pro-chemotherapeutic effects of antibody against extracellular domain of claudin-4 in bladder cancer (2015)
  • Author(s): Masaomi Kuwada, Yoshitomo Chihara, Yi Luo, Xiangru Li, Yukiko Nishiguchi, Rina Fujiwara, Takamistu Sasaki, Kiyomu Fujii, Hitoshi Ohmori, Kiyohide Fujimoto, Masuo Kondoh, Hiroki Kuniyasu
  • Journal Title: Cancer Letters Volume: 369 Issue: 1 Pages: 212-221
  • DOI: 10.1016/j.canlet.2015.08.019
  • Peer Reviewed / Open Access
• [Journal Article] High motility group box 1 induces cancer aggressiveness and drug resistance. (2015)
  • Author(s): Ohmori H, Luo Y, Fujii K, Sasaki T, Kuniyasu H
  • Journal Title: Annals of Clinical Pathology Volume: 3(1) Pages: 1042-1042
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of the plasma free amino acids profiles in cancer patients is associated with dysregulated metabolism in skeletal muscle (2015)
  • Author(s): Luo Y, Yoneda J, Sasaki T, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Archives of Cancer Research Volume: 3(1) Pages: 5-5
  • Peer Reviewed / Open Access
• [Journal Article] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer. (2014)
  • Author(s): Sasaki T, Ohmori H, et al
  • Journal Title: Pathobiology Volume: 81 Issue: 1 Pages: 36-41
  • DOI: 10.1159/000351721
  • Peer Reviewed / Open Access
• [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression. (2014)
  • Author(s): Zhou L, Luo Y, Sato S, Tanabe E, Kitayoshi M, Fujiwara R, Sasaki T, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Pathobiology Volume: 81(4) Issue: 4 Pages: 169-175
  • DOI: 10.1159/000362092
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum CD10 is associated with liver metastasis in colorectal cancer. (2014)
  • Author(s): Sasaki T, Kuniyasu H, Luo Y, Fujiwara R, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y
  • Journal Title: Journal of Surgical Research Volume: 192 Issue: 2 Pages: 390-394
  • DOI: 10.1016/j.jss.2014.05.071
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression. (2014)
  • Author(s): Zhou L, Fujii K, et al
  • Journal Title: Pathobiology Volume: in press
  • Peer Reviewed
• [Journal Article] High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Eur J Cancer Volume: 49 Issue: 3 Pages: 741-751
  • DOI: 10.1016/j.ejca.2012.09.016
  • Peer Reviewed
• [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma. (2013)
  • Author(s): Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
  • Journal Title: Hum Pathol Volume: in press Issue: 6 Pages: 1098-1106
  • DOI: 10.1016/j.humpath.2012.09.016
  • Peer Reviewed
• [Journal Article] Increased phosphorylation of AKT in high-risk gastric mucosa (2013)
  • Author(s): Sasaki T, Fujii K, et al
  • Journal Title: Anticancer Res Volume: 33 Pages: 3295-3300
  • Peer Reviewed
• [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma. (2013)
  • Author(s): Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
  • Journal Title: Hum Pathol Volume: in press
  • Peer Reviewed
• [Journal Article] Significance of epithelial growth factor in the epithelial-mesenchymal transition of human gallbladder cancer cells (2012)
  • Author(s): Sasaki T, Fujii K, et al
  • Journal Title: Cancer Science Volume: (in press) Issue: 6 Pages: 1165-71
  • DOI: 10.1111/j.1349-7006.2012.02264.x
  • Peer Reviewed
• [Journal Article] High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer (2012)
  • Author(s): Luo Y, Ohmori H, Fujii K, Chihara Y, Maruyama S, Kuniyasu H
  • Journal Title: Urol Oncol-Semin Ori Volume: 30 Issue: 3 Pages: 306-313
  • DOI: 10.1016/j.urolonc.2010.05.001
  • Peer Reviewed
• [Journal Article] Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet (2012)
  • Author(s): Shimomoto T, Luo Y, Ohmori H, Chihara Y, Sasahira T, Fujii K, Kuniyasu H
  • Journal Title: J Gastroenterol Volume: 47 Issue: 10 Pages: 1073-83
  • DOI: 10.1007/s00535-012-0572-5
  • NAID: 10031122095
  • Peer Reviewed
• [Journal Article] Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer. (2012)
  • Author(s): Shimomoto T, Ohmori H, Luo Y, Chihara Y, Denda A, Sasahira T, Tatsumoto N, Fujii K, Kuniyasu H
  • Journal Title: Clin Exp Metast Volume: 29 Issue: 8 Pages: 915-925
  • DOI: 10.1007/s10585-012-9480-6
  • Peer Reviewed
• [Presentation] High malignant potential in diabetes-complicated colorectal cancer (2015)
  • Author(s): Kuniyasu H, Fujiwara R, Kishi S, Mori S, Kadochi Y, Fujii K, Sasaki T, Ohmori H.
  • Organizer: 75th Annual Meeting of Japanese Association for Cancer
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Anti-tumor effect by a titanium dioxide nanoparticle (2015)
  • Author(s): Fujiwara R, Luo Y, Kishi S, Fujii K, Sasaki T, Ohmori H, Kuniyasu H
  • Organizer: 75th Annual Meeting of Japanese Association for Cancer
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Triple negative乳癌におけるMAS1の発現 (2015)
  • Author(s): 羅 奕、門地優衣、森 汐莉、森 拓也、岸 真五、笹平智則、佐々木隆光、藤井 澄、大森 斉、國安弘基
  • Organizer: 第24回日本癌転移学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-23
• [Presentation] Cancer stem-like cells and epithelial mesenchymal transition is responsible for failure in bacillus Calmette-Guérin therapy for primary carcinoma in situ. (2015)
  • Author(s): Kuwada M, Chihara Y, Miyake M, Anai S, Tanaka N, Kuniyasu H, Fujimoto K
  • Organizer: Annual Meeting of American Urology Association 2015
  • Place of Presentation: New Orleans
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] 口腔癌におけるアンギオテンシンII２型受容体の意義 (2015)
  • Author(s): 松島紗弥子、羅 奕、田邊絵里子、北吉美沙穂、藤原里奈、藤井 澄、國安弘基
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-30
• [Presentation] 大腸癌粘液腫状間質の骨髄間葉系幹細胞への影響 (2014)
  • Author(s): 藤井 澄、羅 奕、北吉美沙穂、田邊絵里子、藤原里奈、佐々木隆光、國安弘基
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島市
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Association between advanced glycation end products (AGE) and the receptor for AGE in colon carcinogenesis of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet. (2014)
  • Author(s): Shimomoto T, Fujii K, et al
  • Organizer: Society of Toxicology’s 53rd Annual Meeting and ToxExpo
  • Place of Presentation: Phoenix, AZ, USA
• [Presentation] HMGB1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Fujii K, et al
  • Organizer: Merinoff World Congress 2013:HMGB1
  • Place of Presentation: New York, NJ, USA
• [Presentation] HMGB1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Fujii K, et al
  • Organizer: The 18th Japan-Korea Cancer Research Workshop
  • Place of Presentation: Gifu
  • Invited
• [Presentation] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer. (2013)
  • Author(s): Luo Y, Fujii K, et al
  • Organizer: 4th JCA-AACR Special Joint Conference －The Latest Advances in Gastric Cancer Research: From Basic Science to Therapeutics－
  • Place of Presentation: Urayasu
• [Presentation] トランス脂肪酸によるEGFR活性化 (2012)
  • Author(s): 羅 奕、藤井 澄、森若優希子、千原良友、國安弘基
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 大津
• [Presentation] 大腸がんにおける宿主代謝への影響 (2012)
  • Author(s): 國安弘基、羅 奕、栗原 都、笹平智則、千原良友、藤井 澄、大森 斉
  • Organizer: 第27 回発癌病理研究会、シンポジウム5
  • Place of Presentation: 修善寺
• [Presentation] Angiotensin in colorectal cancer metastasis (2012)
  • Author(s): Luo Y, Chihara Y, Ohmori H, Fujii K, Yoshikawa M, Kuwata M, Fujimoto K, Hirao Y, Kitadai Y, Kuniyasu H
  • Organizer: 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Chicago
• [Presentation] トランス脂肪酸によるEGFRのトランス活性化 (2012)
  • Author(s): 藤井 澄、羅 奕、桑田真臣、森若優希子、千原良友、藤本清秀、國安弘基
  • Organizer: 第21回日本がん転移学会
  • Place of Presentation: 広島
• [Presentation] Effect of neutritional starvation on tumor progression (2012)
  • Author(s): Fujii K, Fujiwara R, Luo Y, Kuwada M, Matsushima S, Shimomoto T, Kuniyasu H
  • Organizer: 71st Annual Meeting of Japanese Cancer Association
  • Place of Presentation: 札幌
• [Book] Current Research in Cancer 9 (2015)
  • Author(s): Kuniyasu H, Ohmori H, Fujii K, Iwata N, Katsuragawa H, Fujiwara R, Sasaki T
  • Total Pages: 218
  • Publisher: Significance of trans fatty acids in colorectal cancer.
• [Book] Current Research in Cancer 9 (2015)
  • Author(s): Kuniyasu H, Sasaki T, Fujii K, Ohmori H
  • Total Pages: 165
  • Publisher: Research Media, Kerala, India
• [Book] Current Research in Cancer 8 (2014)
  • Author(s): Kuniyasu H, Luo Y, Yoneda J, Sasaki T, Fujii K, Ohmori H
  • Total Pages: 156
  • Publisher: Research Media, Kerala, India
• [Book] HMGB1 alters the immunity and metabolism of cancer-burden patients. (2013)
  • Author(s): Kuniyasu H, Fujii K, et al
  • Total Pages: 215
  • Publisher: Research Media
• [Remarks] 奈良県立医科大学分子病理学講座
  • URL: http://www.naramed-u.ac.jp/~molepath/