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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• 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, 医学研究科, 准教授 (10285257)
• Co-Investigator(Kenkyū-buntansha): OKUDA Tsukasa 京都府立医科大学, 医学研究科, 教授 (30291587) ; CHIBA Tsutomu 京都大学医学部, 医学研究科, 教授 (30188487)
• Project Period (FY): 2010 – 2012
• Keywords: 胃癌 / 癌抑制遺伝子 / RUNX3

Research Abstract

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. Moreover, clinical application of novel HDAC inhibitor FK228, SAHA, etc. has being carried out. We are examining a carcinogenic inhibiting effect with a mouse chemical carcinogenesis model, and considered that it can applied for the cancer prevention using RUNX3 as the molecular target. 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). Moreover, we are checking generating of a large intestine pathological change by crossing of RUNX3 knockout mouse and an APC knockout mouse. The molecule (TCF4) which the carcinogenic signal transfer system (Wnt signal system) of colorectal cancer and a RUNX3-TGFbeta signal transfer system overlap is also identified (Cancer Cell, Ito et al, 2009), and the further development can expect from now on. 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.

Research Products

• [Journal Article] Total pancreatectomy for pancreatic carcinoma: evaluation of safety and efficacy. (2012)
  • Author(s): M. Kitagawa, H. Ikoma, T. Ochiai, H. Ishii, A. Shiozaki, Y. Kuriu, M. Nakanishi, D. Ichikawa, K. Okamoto, H. Fujiwara,C. Sakakura, Y. Kokuba, T. Sonoyama, E. Otsuji
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 907-910
  • Peer Reviewed
• [Journal Article] Use of Multidetector-row computed tomography to evaluate branch duct type intraductal papillary mucinous neoplasms of the pancreas: influence on surgical decision-making (2011)
  • Author(s): H. Ishii, H. Taniguchi, A. Shiozaki, Y. Kuriu, H. Ikoma, M. Nakanishi, D. Ichikawa, H. Fujiwara, K. Okamoto, T. Ochiai, Y. Kokuba, C. Sakakura, T. Sonoyama, E. Otsuji
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 115-116
  • Peer Reviewed
• [Journal Article] REGIV as a potential biomarker for peritoneal dissemination in gastric adenocarcinoma (2011)
  • Author(s): J.H. Moon, Y. Fujiwara, Y. Nakamura, K. Okada, H. Hanada, C. Sakakura, S. Takiguchi, K. Nakajima, H. Miyata, M. Yamasaki, Y. Kurokawa, M. Mori, Y. Doki
  • Journal Title: J Surg Oncol Volume: 10 Pages: 1002/JSO 22021
  • Peer Reviewed
• [Journal Article] Prognostic impact of microscopic positive margin in gastric cancer patients (2011)
  • Author(s): T. Nagata, D. Ichikawa, S. Komatsu, K. Inoue, A. Shiozaki, H. Fujiwara, K. Okamoto, C. Sakakura, E. Otsuji
  • Journal Title: J Surg Oncol Volume: 104 Pages: 592-597
  • Peer Reviewed
• [Journal Article] OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan (2011)
  • Author(s): H. Yamamoto, M. Sekimoto, M. Oya, N. Yamamoto, F. Konishi, J. Sasaki, S. Yamada, K. Taniyama, H. Tominaga, M. Tsujimoto, H. Akamatsu, A. Yanagisawa, C. Sakakura, Y. Kato, N. Matsuura
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 1891-1898
  • Peer Reviewed
• [Journal Article] Expression of Cancer Stem Cell Markers CD133 and CD44 in Locoregional Recurrence of Rectal Cancer (2011)
  • Author(s): T. Nagata, C. Sakakura, S. Komiyama, A. Miyashita, M. Nishio, Y. Murayama, S. Komatsu, A. Shiozaki, Y. Kuriu, H. Ikoma, M. Nakanishi, D. Ichikawa, H. Fujiwara, K. Okamoto, T. Ochiai, Y. Kokuba, T. Sonoyama and E. Otsuji
  • Journal Title: Anticancer Res Volume: 31 Pages: 495-500
  • Peer Reviewed
• [Journal Article] Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis: Abscess Formation in the Tumor Leading to Bacteremia and Seizure (2010)
  • Author(s): M. Kitagawa, T. Koh , N. Nakagawa, Y. Kondo, M. Nishio, A. Oguro, C. Sakakura, M. Nanri, E. Otsuji
  • Journal Title: Case Rep Gastroenterol Volume: 4 Pages: 435-442
  • Peer Reviewed
• [Journal Article] Salvage surgery for uncontrollable hepatocellular carcinoma treated with repeated non-surgical therapies (2010)
  • Author(s): T. Ochiai, T. Sonoyama, H. Ikoma, Y. Kuriu, M. Nakanishi, T. Kubota, S. Kikuchi, D. Ichikawa, H. Fujiwara, K. Okamoto, C. Sakakura, Y. Kokuba, E. Otsuji
  • Journal Title: Hepatogastroenterology Volume: 57 Pages: 858-864
  • Peer Reviewed
• [Journal Article] RUNX3 promoter methylation in colorectal cancer: its relationship with microsatellite instability and its suitability as a novel serum tumor marker (2010)
  • Author(s): M. Nishio, C. Sakakura, T. Nagata, S. Komiyama, A. Miyashita, T. Hamada, Y. Kuryu, H. Ikoma, T. Kubota, A. Kimura, M. Nakanishi, D. Ichikawa, H. Fujiwara, K. Okamoto, T. Ochiai, Y. Kokuba, T. Sonoyama, H. Ida, K. Ito, T. Chiba, Y. Ito, E. Otsuji
  • Journal Title: Anticancer Res Volume: 30 Pages: 2673-2682
  • Peer Reviewed
• [Journal Article] Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt (2010)
  • Author(s): H. Ishii, T. Sonoyama, S. Nakashima, H. Nagata, A. Shiozaki, Y. Kuriu, H. Ikoma, M. Nakanishi, D. Ichikawa, H. Fujiwara, K. Okamoto, T. Ochiai, Y. Kokuba, C. Sakakura, E. Otsuji
  • Journal Title: World J Gastroenterol Volume: 16 Pages: 3211-3214
  • Peer Reviewed
• [Journal Article] A case report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery (2010)
  • Author(s): T. Ochiai, S. Komiyama, H. Ikoma, T. Kubota, M. Nakanishi, D. Ichikawa, S. Kikuchi, H. Fujiwara, C. Sakakura,Y. Kokuba, T. Sonoyama, E. Otsuji
  • Journal Title: Int J Clin Oncol Volume: 15 Pages: 423-427
  • Peer Reviewed
• [Journal Article] Application of polyethylene glycolic acid felt with fibrin sealant to prevent postoperative pancreatic fistula in pancreatic surgery (2010)
  • Author(s): T. Ochiai, T. Sonoyama, K. Soga, K. Inoue, H. Ikoma, A. Shiozaki, Y. Kuriu, T. Kubota, M. Nakanishi, S. Kikuchi, D. Ichikawa, H. Fujiwara, C. Sakakura, K. Okamoto, Y. Kokuba, E. Otsuji
  • Journal Title: J Gastrointest Surg Volume: 14 Pages: 884-890
  • Peer Reviewed
• [Journal Article] Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer (2010)
  • Author(s): H. Takada, N. Wakabayashi, O. Dohi, K. Yasui, C. Sakakura, S. Mitsufuji, M. Taniwaki, T. Yoshikawa
  • Journal Title: Cancer Genet Cytogenet Volume: 197 Pages: 16-24
  • Peer Reviewed
• [Journal Article] Clinicopathological Characteristics of Colorectal Cancers That Invade the Muscularis Propria (2010)
  • Author(s): A. Miyashita, C. Sakakura, T. Nagata, M. Nishio, T. Hamada, K. Miyagawa, N. Kuriu, H. Ikoma, T. Kubota, M. Nakanishi, D. Ichikawa, S. Kikuchi, H. Fujiwara, K. Okamoto, T. Ochiai, Y. Kokuba, T. Sonoyama, E. Otsuji
  • Journal Title: J Kyoto Pref Univ Med Volume: 119 Pages: 165-174
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of RELN in gastric cancer (2010)
  • Author(s): O. Dohi, O. Dohi, H. Takada, N. Wakabayashi, K. Yasui, C. Sakakura,S. Mitsufuji, Y. Naito, M. Taniwaki, T. Yoshikawa
  • Journal Title: Int J Oncol Volume: 36 Pages: 85-92
  • Peer Reviewed
• [Journal Article] 新消化管の分子生物学(第10回)胃癌の癌抑制遺伝子RUNX3の分子生物学TGF-β/Wntシグナル伝達系とRUNX3は消化器癌にどのようにかかわっているのか? (2010)
  • Author(s): 阪倉長平,大辻英吾
  • Journal Title: G.I.Research Volume: 18 Pages: 151-159
• [Presentation] 胃癌の新取扱い規約ガイドラインの治療成績評価の問題点 (2012)
  • Author(s): 中川登, 今村泰輔, 西村幸寿, 西尾実, 高利守, 阪倉長平, 小黒厚, 岡野晋次, 山根哲郎, 安川林良
  • Organizer: 第84回日本胃癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20120000
• [Presentation] 腹腔鏡下部分切除により切除し得た胃glomus 腫瘍の一例 (2012)
  • Author(s): 阪倉長平, 今村泰輔, 西村幸寿, 西尾実, 高利守, 小黒厚, 中川登
  • Organizer: 第84回日本胃癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20120000
• [Presentation] stageIV 胃癌の長期生存例 stage 規定因子から見た集学的治療(特に手術適応条件)の検討 (2012)
  • Author(s): 中川登, 今村泰輔, 西尾実, 高利守, 阪倉長平, 小黒厚, 岡野晋治, 山根哲郎, 安川林良
  • Organizer: 第112回日本外科学会総会
  • Year and Date: 20120000
• [Presentation] 高度肥満症に対する減量消化管手術を安全に行うための手術手技と周術期の要点-われわれの経験から- (2012)
  • Author(s): 萩原明於, 小座本雄軌, 戸川剛, 大辻英吾, 阪倉長平, 吉田俊秀, 川村功
  • Organizer: 第112回日本外科学会総会
  • Year and Date: 20120000
• [Presentation] 直腸癌 DST 吻合における縫合不全リスク因子の検討と Covering ileostomy の問題点 (2012)
  • Author(s): 阪倉長平, 今村泰輔, 西尾実, 高利守, 小黒厚, 中川登
  • Organizer: 第112回日本外科学会総会
  • Year and Date: 20120000
• [Presentation] 肥満症に対する腹腔鏡した襟状胃切除の手術手技・周術期管理の工夫と術後1年以上経過時の治療成績 (2012)
  • Author(s): 阪倉長平, 小座本雄軌, 戸川剛, 大辻英吾, 萩原明於, 川村 功
  • Organizer: 第67回日本消化器外科学会総会
  • Place of Presentation: 富山
  • Year and Date: 20120000
• [Presentation] 微粒子活性炭による胃リンパ流検索に基づくリンパ節廓清 (2012)
  • Author(s): 中川登, 今村泰輔, 西村幸寿, 西尾実, 高利守, 阪倉長平, 小黒厚, 岡野晋次, 山根哲郎, 安川林良
  • Organizer: 第67回日本消化器外科学会総会
  • Place of Presentation: 富山
  • Year and Date: 20120000
• [Remarks] 大学ホームページ
  • URL: http://www.kpu-m.ac.jp/k/dgstv-surg/