Development of epigenetic biomarker for early diagnosis of gastrointestinal cancer

• Project/Area Number: 19390351
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: MATSUBARA Nagahide Okayama University, 医学部・歯学部附属病院, 助教 (70314672)
• Co-Investigator(Kenkyū-buntansha): TANAKA Noriaki 岡山大学, 大学院・医歯薬学総合研究科, 教授 (10127566) ; SHIMIZU Kenji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (10037286) ; NAGASAKA Takeshi 岡山大学, 医学部・歯学部附属病院, 助教 (30452569)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 大腸癌 / スクリーニング / DNAメチル化 / 消化器癌 / 早期診断 / epigenetic alteration

Research Abstract

日本人の死因における第一位が癌になって久しいが、癌の中では大腸癌が今や第一位とならんとしており、大腸癌はまさに国民病といって過言ではない。大腸癌は切除可能な時期に診断されれば、治癒する可能性の非常に高い癌である。従って大腸癌の激減をめざそうとすれば、癌の早期診断に勝るものは無い。しかし、現行の大腸癌検診の受診率は18%にとどまり、要精検率は7%前後、要精検者のうち大腸癌が見つかったのは約2%にすぎない。我々は、簡便さを落とさず、癌由来のDNAを便中に検出するすぐれた方法を開発した。

Research Products

• [Journal Article] Mutations in both KRAS and BRAF contribute to the methylator phenotype in colon cancer (2008)
  • Author(s): Takeshi Nagasaka, Minoru Koi, Matthias Kloor, Johannes Gebert, Alex Vilkin, Naoshi Nishida, Sung Kwan Shin, Hiromi Sasamoto, Noriaki Tanaka, Nagahide Matsubara, C. Richard Boland, and Ajay Goel
  • Journal Title: Gastroenterology 134 Pages: 1950-1960
  • Peer Reviewed
• [Journal Article] Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis (2008)
  • Author(s): Takeshi Nagasaka, Ajay Goel, Kenji Notohara, Takaomi Takahata, Hiromi Sasamoto, Takuyuki Uchida, Naoshi Nishida, Noriaki Tanaka, C. Richard Boland, Nagahide Matsubara
  • Journal Title: Int. J. Cancer 122 Pages: 2429-2436
  • Peer Reviewed
• [Journal Article] リンチ症候群screening上の課題 (2008)
  • Author(s): 松原長秀
  • Journal Title: 家族性腫瘍 8 Pages: 58-60
  • NAID: 130007535222
  • Peer Reviewed
• [Journal Article] Mutations in both KRAS and BRAF contribute to the methylator phenotype in colon cancer. 134 : 1950-1960 (2008) (2008)
  • Author(s): Nagasaka T. Koi M, Kloor M, Gebert J, Vilkin A, Nishida N, Shin S-K, Sasamoto H, Tanaka N, Matsubara N, Bol, C R, Goel A
  • Journal Title: Gastroenterology 134 Pages: 1950-1960
  • Peer Reviewed
• [Journal Article] Methylation pattern of the 06-methylguanlne一DNA methyltransferase gene in colon during progressive colorectal tumorigenesis. 122 : 2429-2436 (2008) (2008)
  • Author(s): Nagasaka T, Goel Ajay, KenjiNotohara, Takaomi Takahata, Hiromi Sasamoto, Takuyuki Uchida, NaoshiNishida, Noriaki Tanaka, C. Richard Boland, Nagahide Matsubara
  • Journal Title: Int. J. Cancer 122 Pages: 2429-2436
  • Peer Reviewed
• [Journal Article] Epigenetic and Genetic Alterations in Netrin-1 Receptors UNC5C and DCC in Human Colon Cancer (2007)
  • Author(s): Sung Kwan Shin, Takeshi Nagasaka, Barbara H. Jung, Nagahide Matsubara, Won Ho Kim, John M. Carethers, C. Richard Boland, and Ajay Goel
  • Journal Title: Gastroenterology 133 Pages: 1849-1857
  • Peer Reviewed
• [Journal Article] Microsatellite instability and clinicopathological features in esophageal squamous cell cancer (2007)
  • Author(s): Matsumoto, Y., Nagasaka, T., Kambara, T., Hoshizima, N., Murakami, J., Sasamoto, H., Hosokawa, M., Naomoto, Y., Isozaki, H., Shimizu, K., Tanaka, N., Matsubara, N.
  • Journal Title: Oncol. Rep. 18 Pages: 1123-1127
  • Peer Reviewed
• [Journal Article] Depletion of O6-methylguanine-DNA methyltransferase by O6-benzylguanine enhances 5-FU cytotoxicity in colon and oral cancer cell lines (2007)
  • Author(s): Murakami J, Lee YJ, Kokeguchi S, Tsujigiwa H, Asaumi J, Nagatsuka H, Fukui K, Kuroda M, Tanaka N, Matsubara N.
  • Journal Title: Oncol. Rep. 17(6) Pages: 1461-1467
  • Peer Reviewed
• [Journal Article] No duplicate KRAS mutation is identified on the same allele of gastric or colorectal cancer cells with multiple KRAS mutations (2007)
  • Author(s): Kimura, K., Nagasaka, T., Sasamoto, H., Notohara, K., Takeda, M., Komnami, K., Ishii, T., Tanaka, N., Matsubara, N.
  • Journal Title: J. Int. Med. Res 35 Pages: 450-457
  • Peer Reviewed
• [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa (2007)
  • Author(s): Ishii, T., Murakami, J., Notohara, K., Cullings, H. M., Sasamoto, H., Kambara, T., Shirakawa, Y., Naomoto, Y., Ouchida, M., Shimizu, K., Tanaka, N., Jass, J. R., Matsubara, N.
  • Journal Title: Gut 56 13-19
  • Peer Reviewed
• [Journal Article] 便中DNAによる大腸癌発見法(1週1話) (2007)
  • Author(s): 松原長秀
  • Journal Title: 医事新報 4326 : 85
  • Peer Reviewed
• [Journal Article] リンチ症候群のリクルートにおける病理組織・免疫染色・MSIテスト・somatic遺伝子検査の意義 (2007)
  • Author(s): 松原長秀、永坂岳司、田中紀章
  • Journal Title: 家族性腫瘍 7 Pages: 11-14
  • NAID: 130007540975
  • Peer Reviewed
• [Journal Article] Oesophageal squamous cell cancer may develop within a back ground of accumulating DNA methylation in normal and dys plastic mucosa. (2007)
  • Author(s): Ishii, T., Murakami, J., Notohara, K., Cullings, H.M., Sasamoto, H., Kambara, T., Shirakawa, Y., Naomoto, Y., Ouchida, M., Shimizu, K., Tanaka, N., Jass, J. R., Matsubara, N.
  • Journal Title: Gut 56, Pages: 13-19
  • Peer Reviewed
• [Journal Article] No duplicate KRAS mutation is identified on the same allele of gastric or colorectal cancer cells with multiple KRAS mutations. (2007)
  • Author(s): Kimura, K., Nagasaka, T., Sasamoto, H., Notohara, K., Takeda, M., Komnami, K., Ishii, T., Tanaka, N., Matsubara, N.
  • Journal Title: J. Int. Med. Res. 35 Pages: 450-457
  • Peer Reviewed
• [Journal Article] Depletion of O6-methylguanine-DNA methyltransferase by O6-benzylguanine enhances 5-FU cytotoxicity in colon and oralcancer cell lines. (2007)
  • Author(s): Murakami J, Lee YJ, Kokeguchi S, Tsujigiwa H, Asaumi J, Nagatsuka H, Fukui K, Kuroda M, Tanaka N, Matsubara N.
  • Journal Title: Onclo. Rep. 17(6): Pages: 1461-1467
  • Peer Reviewed
• [Journal Article] Microsatellite instability and clinicopathological features in esophageal squamous cell cancer. (2007) (2007)
  • Author(s): Matsumoto, Y., Nagasaka, T., Kambara, T., Hoshizima N., Murakami, J., Sasamo to, H., Hosokawa, M., Naomoto, Y., Isozaki, H., Shimizu, K., Tanaka, N., Matsubara, N.
  • Journal Title: Oncol. Rep. 18, Pages: 1123-1127
  • Peer Reviewed
• [Journal Article] Epigenetic and Genetic Alterations in Netrin-1 Receptors UNC5C and DCC in Human Colon Cancer.(2007) (2007)
  • Author(s): Sung Kwan Shin, Takeshi Nagasaka, Barbara H. Jung, Nagahide Matsubara, Won Ho Kim, John M. Carethers, C. Richard Boland, and Aiay Goel
  • Journal Title: Gastroenterology 133: Pages: 1849-1857
  • Peer Reviewed
• [Journal Article] Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis (2007) (2007)
  • Author(s): Takeshi Nagasaka, Ajay Goel, Kenji Notohara, Takaomi Takahata, Hiromi Sasamoto, Takuyuki Uchida, Naoshi Nishida, Noriaki Tanaka, C. Richard Boland, Nagahide Matsubara
  • Journal Title: Int. J. Cancer (In press)
  • Peer Reviewed
• [Presentation] 大腸癌のepigenetic変異をコントロールするパスウェイとこれに基づく亜分類の診断・治療への応用 (2008)
  • Author(s): 松原長秀、永坂岳司、近藤喜太、田中紀章
  • Organizer: 第63回日本大腸肛門病学会学術集会
  • Place of Presentation: ホテル日航東京(パネルディスカッション)
• [Presentation] Does laparoscopic surgery for colorectal cancer really contribute a lot to the post-operative patient's life (2008)
  • Author(s): Nagahide Matsubara, Yoshitaka Kondo, Naoya Kobayashi, Noriaki Tanaka
  • Organizer: 11^<th> World Congress of Endoscopic Surgery
  • Place of Presentation: Yokohama, Japan(Workshop)
• [Presentation] 大腸癌鋸歯状病変よりの発癌機構と大腸癌に於ける位置づけ (2008)
  • Author(s): 松原長秀,長尾厚樹,神原健,田中紀章
  • Organizer: 第19回日本消化器癌発生学会総会
  • Place of Presentation: 別府亀の井ホテル(ミニシンポジウム)
• [Presentation] 大腸癌の前癌病変を含めた早期診断法の確立とtranslational researchへの問題点 (2008)
  • Author(s): 松原長秀、永坂岳司、内田卓之、笹本博美、戸田桂介、谷口信将、岡哲弘、田中紀章
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 札幌(ワークショップ)
• [Presentation] 便中DNAによる大腸癌発見法 (2008)
  • Author(s): 松原長秀、永坂岳司、田中紀章
  • Organizer: 第14回日本家族性腫瘍学会学術集会
  • Place of Presentation: 国立がんセンター東京(シンポジウム)
• [Presentation] 大腸癌のepigenetic変異をコントロールするパスウェイとこれに基づく亜分類の診断・治療への応用 (2008)
  • Author(s): 松原長秀, 永坂岳司, 近藤喜太, 田中紀章
  • Organizer: 第63回日本大腸肛門病学会学術集会
  • Place of Presentation: ホテル日航東京
• [Presentation] 大腸鋸歯状ポリープよりの発癌機構とその病変の大腸癌における位置づけ (2007)
  • Author(s): 松原長秀、長尾厚樹、神原健、田中紀章
  • Organizer: 第88回日本消化器病学会中国支部例会
  • Place of Presentation: 岡山コンベンションセンター岡山
• [Presentation] リンチ症候群の大腸癌におけるepigeneticの関与 (2007)
  • Author(s): 松原長秀、永坂岳司、神原健、田中紀章
  • Organizer: 第45回日本癌治療学会総会
  • Place of Presentation: 京都
• [Presentation] Geand epigenetic alteratons in Lynch syndrome and sporadic colorectal cancers (2007)
  • Author(s): Nagahide Matsubara
  • Organizer: 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama(Symposia, International Sessions)
• [Presentation] HNPCC screening上の課題 : シンポジウム[家族性腫瘍-基礎と臨床] (2007)
  • Author(s): 松原長秀, 永坂岳司, 能登原憲司, 笹本博美, 田中紀章
  • Organizer: 第13回日本家族性腫瘍学会
  • Place of Presentation: 高知
• [Presentation] Multimodal treatment for rectal cancer. Symposium : Current topics of the surgical treatment for rectal cancer (2007)
  • Author(s): Nagahide Matsubara, Noriaki Tanaka
  • Organizer: The International College of Surgeons. 17^<th> Joint Congress of Asia & Pacific Federations & 53^<rd> Annual Congress of the Japanese Section
  • Place of Presentation: Westin Miyako Hotel Kyoto, Kyoto, Japan.
• [Book] 大腸鋸歯病変の分子生物学的特徴 大腸疾患NOW2008 武藤徹一郎監修杉原健一・藤盛孝博・五十嵐正広・渡邉聡明編集 (2008)
  • Author(s): 松原長秀
  • Total Pages: 210
  • Publisher: 日本メディカルセンター
• [Book] 大腸疾患NOW2008 (2008)
  • Author(s): 松原長秀(分担執筆)
  • Total Pages: 203
  • Publisher: 日本メディカルセンター
• [Book] 大腸鋸歯病変の分子生物学的特徴大腸疾患NOW2008(武藤徹一郎監修 杉原健一・藤盛孝博・五十嵐正広・渡邉聡明編集)
  • Author(s): 松原長秀
  • Publisher: 日本メディカルセンター
• [Patent(Industrial Property Rights)] メチル化核酸又は非メチル化核酸を増幅する方法 (2007)
  • Inventor(s): 永坂岳司、松原長秀、田中紀章
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 2007-153086
  • Filing Date: 2007-06-08
• [Patent(Industrial Property Rights)] メチル化核酸又は非メチル化核酸を増幅する方法 (2007)
  • Inventor(s): 永坂岳司, 松原長秀, 田中紀章, 笹本博美
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 2007-153086
  • Filing Date: 2007-06-08