Nalysis of novel tumor suppressor gene RUNX3 of gastric cancer and clinical application for the diagnosis and prevention of gastric cancer

• Project/Area Number: 16K10512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Sakakura Chouhei 京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (10285257)
• Co-Investigator(Kenkyū-buntansha): 阪口 晃一 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00405284) ; 奥田 司 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587) ; 小西 英幸 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30295670)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胃癌 / 癌抑制遺伝子 / 発癌予防 / RUNX3 / 遺伝子診断

Outline of Final Research Achievements

Based on the analysis result of RUNX3 knockout mouse as well as clinical samples of gastric cancer, the following was developed aiming at the functional analysis of RUNX3, and gene diagnosis and the application to carcinogenic prevention and medical treatment. We have already identified several kinds of markers of a gastric cancer precursor cell, and are looking for a stomach cancer precursor cell in the background membrane of an early frequent occurrence stomach cancer excision specimen. Furthermore, RUNX3 has played the role important for TGFbeta dependence apoptosis, and participating in the susceptibility of a radiation chemistry treatment became clear (Oncogene, Sakakura et al., 2007).
With Luminex system, we establish the quick serological-diagnosis system which can measure quantitatively methylation of two or more genes in many samples in a short time, and are trying for clinical application.

Academic Significance and Societal Importance of the Research Achievements

これまで発癌機序が明らかでなかった胃癌の新規癌抑制遺伝子RUNX3のクローニングと機能解析の成果に基づき、各種消化器癌や乳癌や肺癌の遺伝子診断や発癌予防などの臨床応用が可能となりつつある。

Research Products

• [Journal Article] Needlescopic surgery for broad ligament hernia: A case report. (2018)
  • Author(s): Koizumi N, Ariyoshi Y, Fujiki H, Sakakura C
  • Journal Title: Asian J Endoscopic Sure Volume: 20 Issue: 1 Pages: 100-102
  • DOI: 10.1111/ases.12692
  • Peer Reviewed / Open Access
• [Journal Article] Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. (2018)
  • Author(s): Iizuka-Ohashi M1,2, Watanabe M1, Sukeno M1, Morita M1, Hoang NTH3, Kuchimaru T, Kizaka-Kondoh S, Sowa Y1 Sakaguchi K, Taguchi T, Sakai T.
  • Journal Title: Oncotarget. Volume: 9 Issue: 28 Pages: 19597-19612
  • DOI: 10.18632/oncotarget.24696
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy of Magnifying Narrow Band Imaging for Delineating Horizontal Margins of Early Gastric Cancer (2018)
  • Author(s): Horii Y, Dohi O, Naito Y, Ogita K, Terasaki K, Konishi H, et al
  • Journal Title: Digestion Volume: 10 Issue: 2 Pages: 1-7
  • DOI: 10.1159/000494053
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Clutch Cutter for Standardizing Endoscopic Submucosal Dissection for Early Gastric Cancer: APropensity Score-Matched Analysis (2018)
  • Author(s): Dohi O, Yoshida N, Terasaki K, Azıma Y, Konishi H, et al
  • Journal Title: Digestion Volume: 10 Issue: 3 Pages: 1-9
  • DOI: 10.1159/000495287
  • Peer Reviewed / Open Access
• [Journal Article] Acase of Esophageal Gastrointestinal Stromal Tumor Resected by Mediastinoscope-Assisted Transhiatal Esophagectomy (2018)
  • Author(s): Ariyosi Y, Koizumi N, Sakakura C, et al
  • Journal Title: Gan to Kagaku Ryoho Volume: 45(13) Pages: 2267-2269
  • Peer Reviewed
• [Journal Article] The protective effect of orally administered redox nanoparticle on intestinal ischemia-reperfusion injury in mice. (2018)
  • Author(s): Ueda T, Takagi T, Katada K, Iida T, Mizushima K, Dohi O, Okayama T, Yoshida N, Kamada K, Uchiyama K, Handa O, Ishikawa T, Konishi H, Naito Y, Nagasaki Y, Itoh Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 495 Issue: 2 Pages: 2044-2049
  • DOI: 10.1016/j.bbrc.2017.11.204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular heterogeneity in APIP-FGFR2 fusion transcripts with diversity of genomic breakpoints in gastric cancer high-level amplifications at 11p13 and 10q26 (2017)
  • Author(s): Okuda T, Taki T, Nishida K Chinen Y, Nagoashi H, Sakakura C, Ohtsuji E, Taniwaki M
  • Journal Title: Oncol Lett Volume: 13 Issue: 1 Pages: 215-221
  • DOI: 10.3892/ol.2016.5386
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Early-Stage Gastric Cancer Can Be Found in Improved Atrophic Mucosa over Time from Successful Helicobacter pylori Eradication. (2017)
  • Author(s): Majima A1, Handa O, Naito Y, Dohi O, Okayama T, Yoshida N, Kamada K, Katada K, Uchiyama K, Ishikawa T, Takagi T, Konishi H, Yagi N, Itoh Y.
  • Journal Title: Digestion Volume: 95(3) Issue: 3 Pages: 194-200
  • DOI: 10.1159/000460245
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The number of metastatic lymph nodes exhibiting poorly differentiated clusters predicts survival in patients with pStage III colorectal cancer. (2016)
  • Author(s): Kinoshita O, Kishimoto M, Murayama Y, Kuriu Y, Nakanishi M, Sakakura C, Otsuji E, Yanagisawa A
  • Journal Title: Int J Colorectal Dis. Volume: 31(2) Issue: 2 Pages: 283-90
  • DOI: 10.1007/s00384-015-2393-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells. (2016)
  • Author(s): Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M.
  • Journal Title: Cancer Cell Volume: 29 Pages: 935-948
  • DOI: 10.1016/j.canlet.2017.04.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection. (2014)
  • Author(s): Fujiwara H, Shiozaki A, Konishi H, Komatsu S, Kubota T, Ichikawa D, Okamoto K, Morimura R, Murayama Y, Kuriu Y, Ikoma H, Nakanishi M, Sakakura C, Otsuji E.
  • Journal Title: Dis Esophagus. Volume: Published online Issue: 2 Pages: 131-138
  • DOI: 10.1111/dote.12303
  • Peer Reviewed / Open Access