A systematic study of the disorders in the spindle assembly checkpoint genes in colorectal cancer and its application to molecular targeted therapy

• Project/Area Number: 23591964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: KOHNOE Shunji 九州大学, 医学(系)研究科(研究院), 共同研究員 (30215199)
• Co-Investigator(Kenkyū-buntansha): TSUJITANI Shunichi 九州大学, 医学研究院, 准教授 (30188544) ; KAKEJI Yoshihiro 神戸大学, 医学研究科, 教授 (80284488) ; MORITA Masaru 九州大学, 医学研究院, 准教授 (30294937) ; OHGA Takefumi 九州大学, 大学病院, 助教 (60335958) ; EGASHIRA Akinori 九州大学, 大学病院, 特任助教 (00419524) ; SONODA Hideto 九州大学, 大学病院, 特任助教 (00465725) ; KITAO Hiroyuki 九州大学, 医学研究院, 准教授 (30368617)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / ゲノム不安定性 / 染色体不安定性 / スピンドルチェックポイント / DNA aneuploidy / BUBR1 / Aurora-A / Aurora-B / PLK1 / 発がん

Research Abstract

In order to elucidate the molecular abnormality in colorectal carcinogenesis, we investigate the disorders in the spindle assembly checkpoint genes by examining those expressions in colorectal cancer cell. Our data showed that p53 gene mutation (loss of normal function) might induce suppression of spindle assembly checkpoint genes, and might contribute to DNA aneuploidy and thereafter carcinogenesis.

Research Products

• [Journal Article] Mortalin is a prognostic factor of gastric cancer with normal p53 function (2014)
  • Author(s): Ando K, Oki E, Zhao Y, Yoshida A, Kitao H, Saeki H, Kimura Y, Ida S, Morita M, Kusumoto T, Maehara Y.
  • Journal Title: Gastric Cancer Volume: 17(2) Pages: 255-262
• [Journal Article] Contribution of Aurora-A and–B expression to DNA aneuploidy in gastric cancer (2014)
  • Author(s): Honma K, Nakanishi R, Nakanoko T, Ando K, Saeki H, Oki E, Iimori M, Kitao H, Kakeji Y, Maehara Y.
  • Journal Title: Surg Today Volume: 44(3) Pages: 454-461
• [Journal Article] Mortalin is a prognostic factor of gastric cancer with normal p53 function. (2014)
  • Author(s): Ando K., Oki E., Zhao Y., Yoshida A., Kitao H., Saeki H., Kimura Y., Ida S., Morita M., Kusumoto T., Maehara Y.
  • Journal Title: Gastric Cancer Volume: 17(2) Issue: 2 Pages: 255-262
  • DOI: 10.1007/s10120-013-0279-1
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of Auroa-A and -B expression to DNA aneuploidy in gastric cancers. (2014)
  • Author(s): Honma K., Nakanishi R., Nakanoko T., Ando K., Saeki H., Oki E., Iimori M., Kitao H., Kakeji Y., Maehara Y.
  • Journal Title: Surgery Today Volume: 44(3) Issue: 3 Pages: 454-461
  • DOI: 10.1007/s00595-013-0581-x
  • Peer Reviewed / Open Access
• [Journal Article] Congribution of BubR1 to oxidative stress-induced aneuploidy in p53- deficient cells (2013)
  • Author(s): Ikawa-Yoshida A, Ando K, Oki E, Saeki H, Kumashiro R, Taketani K, Ida S, Tokunaga E, Kitao H, Morita M, Maehara Y.
  • Journal Title: Cancer Medicine Volume: 2(4) Pages: 447-456
• [Journal Article] 分子標的薬に対する期待と課題 (2013)
  • Author(s): 沖英次、佐伯浩司、安藤幸滋、井田智、木村和恵、森田勝、楠本哲也、前原喜彦
  • Journal Title: 臨床と研究 Volume: 90 Pages: 68-72
• [Journal Article] Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer (2013)
  • Author(s): Nakanishi R, Harada J, Tuul M, Zhao Y, Ando K, Saeki H, Oki E, Ohga T, Kitao H, Kakeji Y, Maehara Y.
  • Journal Title: Int J Clin Oncol Volume: 18(6) Pages: 1042-1048
• [Journal Article] Contribution of BubR1 to oxidative stress-induced aneuploidy in p53-deficient cells. (2013)
  • Author(s): Ikawa-Yoshida A., Ando K., Oki E., Saeki H., Kumashiro R., Taketani K., Ida S., Tokunaga E., Kitao H., Morita M., Maehara Y.
  • Journal Title: Cancer Medicine Volume: 2(4) Issue: 4 Pages: 447-456
  • DOI: 10.1002/cam4.101
  • Peer Reviewed
• [Journal Article] ATR-Chk1 signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity (2012)
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto K, Takata M, Kitao H, Maehara Y.
  • Journal Title: DNA Repair Volume: 11(3) Pages: 247-258
• [Journal Article] FANCJ Expression Predicts the Response to 5-Fluorouracil-Based Chemotherapy in MLH1-Proficient Colorectal Cancer (2012)
  • Author(s): Nakanishi R, Kitao H, Fujinaka Y, Yamashita N, Iimori M, Tokunaga E, Yamashita N, Morita M, Kakeji Y, Maehara Y.
  • Journal Title: Ann Surg Oncol Volume: 19(11) Pages: 3627-3635
• [Journal Article] Clinical aspect and molecular mechanism of DNA aneuploidy in gastric cancers (2012)
  • Author(s): Oki E, Hisamatsu Y, Ando K, Saeki H, Kakeji Y, Maehara Y.
  • Journal Title: J Gastroenterol Volume: 47(4) Pages: 351-358
  • NAID: 10030649711
• [Journal Article] CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication (2012)
  • Author(s): Sakasai R, Sakai A, Iimori M, Kiyonari S, Matsuoka K, Kakeji Y, Kitao H, Maehara Y.
  • Journal Title: Genes Cells Volume: 17(12) Pages: 962-970
• [Journal Article] PARP and CSB modulate the processing of transcription-mediated DNA strand breaks (2012)
  • Author(s): Sakai A, Sakasai R, Kakeji Y, Kitao H, Maehara Y.
  • Journal Title: Genes Genetic Systems Volume: 87(4) Pages: 265-272
  • NAID: 10031126619
• [Journal Article] 胃癌における紡錘体形成チェックポイントタンパク質の発現異常とDNA aneuploidy (2012)
  • Author(s): 安藤幸滋、北尾洋之、飯森真人、沖英次、佐伯浩司、大賀丈史、掛地吉弘、辻谷俊一、鴻江俊治、前原喜彦
  • Journal Title: 胃がんperspective Volume: 5(1) Pages: 24-32
• [Journal Article] ATR-Chkl signaling pathway and homologous recombinational repair protect cells from 5-fluorouracil cytotoxicity (2012)
  • Author(s): Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto KI, Takata M, Kitao H, Maehara Y
  • Journal Title: DNA Repair Volume: 1(3) Issue: 3 Pages: 247-58
  • DOI: 10.1016/j.dnarep.2011.11.005
  • Peer Reviewed
• [Journal Article] FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer (2012)
  • Author(s): Nakanishi, et al
  • Journal Title: Annals of Surgical Oncology Volume: (In press) Issue: 11 Pages: 3627-35
  • DOI: 10.1245/s10434-012-2349-8
  • Peer Reviewed
• [Journal Article] The Q Motif of Fanconi Anemia Group J Protein (FANCJ) DNA Helicase Regulates Its Dimerization, DNA Binding, and DNA Repair Function. (2012)
  • Author(s): Wu Y., Sommers JA., Loiland JA., Kitao H., Kuper J., Kisker C., Brosh RM Jr.
  • Journal Title: J Biol Chem Volume: 287(26) Issue: 26 Pages: 21699-716
  • DOI: 10.1074/jbc.m112.351338
  • Peer Reviewed
• [Journal Article] Clinical aspect and molecular mechanism of DNA aneuploidy in gastric cancers. (2012)
  • Author(s): Oki E., Hisamatsu Y., Ando K., Saeki H.,Kakeji Y., Maehara Y.
  • Journal Title: J Gastroenterol Volume: 47(4) Issue: 4 Pages: 351-8
  • DOI: 10.1007/s00535-012-0565-4
  • NAID: 10030649711
  • Peer Reviewed
• [Journal Article] CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication. (2012)
  • Author(s): Sakasai R., Sakai A., Iimori M., Kiyonari S., Matsuoka K., Kakeji Y., Kitao H., Maehara Y.
  • Journal Title: Genes Cells Volume: 17(12) Issue: 12 Pages: 962-70
  • DOI: 10.1111/gtc.12011
  • Peer Reviewed
• [Journal Article] Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair (2012)
  • Author(s): Koichi Sato. Masamichi Ishiai, Kazue Toda, Satoshi Furukoshi, Akihisa Osakabe, Hiroaki Tachiwana, Yoshimasa Takizawa, Wataru Kagawa, Hiroyuki Kitao, Naoshi Dohmae, Chikashi Obuse, Hiroshi Kimura, Minoru Takata, Hitoshi Kurumizaka
  • Journal Title: The EMBO Journal Volume: 31 Issue: 17 Pages: 3524-3536
  • DOI: 10.1038/emboj.2012.197
  • Peer Reviewed
• [Journal Article] PARP and CSB modulate the processing of transcription-mediated DNA strand breaks. (2012)
  • Author(s): Sakai A., Sakasai R., Kakeji Y., Kitao H., Maehara Y.
  • Journal Title: Genes Genetic Systems Volume: 87(4) Pages: 265-72
  • NAID: 10031126619
  • Peer Reviewed
• [Journal Article] Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer. (2012)
  • Author(s): Nakanishi R., Harada J., Tuul M., Zhao Y., Ando K., Saeki H., Oki E., Ohga T., Kitao H., Kakeji Y.,
  • Journal Title: Int J Clin Oncol Volume: Nov 29
  • Peer Reviewed
• [Journal Article] Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer (2012)
  • Author(s): Tsujitani S, Saito H, Wakatsuki T, Ikeguchi M, Shirabe K, Morita M, Kakeji Y, Yano T, Maehara Y
  • Journal Title: Surg Today Volume: 42 Issue: 3 Pages: 225-32
  • DOI: 10.1007/s00595-011-0062-z
  • NAID: 10030231066
  • Peer Reviewed
• [Journal Article] 胃癌における紡錘体形成チェックポイントタンパク質の発現異常とDNA aneuploidy (2012)
  • Author(s): 安藤 幸滋、北尾 洋之、飯森 真人、沖 英次、佐伯 浩司、大賀 丈史、掛地 吉弘、辻谷 俊一、鴻江 俊治、前原 喜彦
  • Journal Title: 胃がんperspective Volume: 5(1) Pages: 224-224
  • Peer Reviewed
• [Journal Article] 消化器癌におけるDNA aneuploidy の意義 (2012)
  • Author(s): 安藤 幸滋、趙岩、沖 英次、北尾 洋之、佐伯 浩司、掛地吉 弘、木村 和恵、井田 智、森田 勝、楠本 哲也、前原 喜彦
  • Journal Title: CYTOMETRY RESEARCH Volume: 22(2) Pages: 15-20
  • NAID: 10031026118
  • Peer Reviewed
• [Journal Article] 消化器癌におけるDNA aneuploidyの意義
  • Author(s): 安藤幸滋、趙岩、沖英次、北尾洋之、佐伯浩司、掛地吉弘、木村和恵、井田智、森田勝、楠本哲也、前原喜彦
  • Journal Title: CYTOMETRY RESEARCH Volume: 22(2) Pages: 15-20
  • NAID: 10031026118
• [Presentation] 胃癌における細胞周期の制御因子Plk1過剰発現と染色体不安定性の関連 (2013)
  • Author(s): 大津甫、笠木勇太、財津瑛子、日高元、津田康雄、河野浩幸、安藤幸滋、井田智、木村和恵、佐伯浩司、沖英次、森田勝、楠本哲也、前原喜彦
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡市
• [Presentation] Loss of heterozygosity of encoding phosphate and tensin homolog as a prognostic factor in for gastric cancer, and it's relatsionship with p53 (2013)
  • Author(s): Zaitsu Y, Oki E, Tanaka K, Yukaya T, Kasagi Y, Tsuda Y, Hidaka G, Otsu H, Kawano H, Ando K, Ida S, Kimura Y, Saeki K, Morita M, Kusumoto T, Maehara Y.
  • Organizer: The 10th International Gastric Cancer Congress(IGCC 2013)
  • Place of Presentation: ヴェローナ(イタリア)
• [Presentation] ヒト大腸がん細胞のTRAILシグナルにおけるストレス応答遺伝子ATF3とp53と協調作用 (2013)
  • Author(s): 武谷憲二、安藤幸滋、井田智、木村和恵、佐伯浩司、沖英次、森田勝、楠本哲也、北嶋繁孝、前原喜彦
  • Organizer: 第24回日本消化器癌発生学会
  • Place of Presentation: 金沢市
• [Presentation] Loss of heterozygosity of encoding phosphate and tensin homolog as a prognostic factor for gastric cancer, and it’s relationship with p53. (2013)
  • Author(s): Zaitsu Y., Oki E., Tanaka K., Yukaya T., Kasagi Y., Tsuda Y., Hidaka G., Otsu H., Kawano H., Ando K., Ida S., Kimura Y., Saeki K., Morita M., Kusumoto T., Maehara Y.
  • Organizer: The 10th International Gastric Cancer Congress(IGCC 2013)
  • Place of Presentation: ヴェローナ（イタリア）
• [Presentation] ヒト大腸がん細胞のTRAILシグナルにおけるストレス応答遺伝子ATF3とp53と協調作用 (2013)
  • Author(s): 武谷 憲二、安藤 幸滋、井田 智、木村 和恵、佐伯 浩司、沖 英次、森田 勝、楠本 哲也、北嶋 繁孝、前原 喜彦
  • Organizer: 第24回日本消化器癌発生学会総会
  • Place of Presentation: 金沢市
• [Presentation] 大腸癌におけるKRAS, BRAF変異とマイクロサテライト不安定性 (2012)
  • Author(s): 中西良太、趙岩、北尾洋之、安藤幸滋、佐伯浩司、大賀丈史、沖英次、掛地吉弘、辻谷俊一、鴻江俊治、前原喜彦
  • Organizer: 第45回制癌剤適応研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-03-02
• [Presentation] Significance of mortalin expression in gastric cancer with normal p53 (2012)
  • Author(s): Ando K, Oki E, Yan Z, Kitao H, Saeki H, Ohga T, Kakeji Y, Tujitani S, Kohnoe S, Maehara Y.
  • Organizer: ASCO GI 2012
  • Place of Presentation: サンフランシスコ
• [Presentation] Prognostic role of KRAS and BRAF mutations in Japanese patients with colorectal cancer (2012)
  • Author(s): Oki E, Nakanishi R, Ando K, Saeki H, Ohga T, Kakeji Y, Tujitani S, Kohnoe S, Maehara Y.
  • Organizer: ASCO
  • Place of Presentation: シカゴ
• [Presentation] (2012)
  • Author(s): Nakanishi R, Kitao H, Fujinaka Y, Yamashita N, Iimori M, Tokunaga E, Yamashita N, Morita M, Kakeji Y, Maehara Y.
  • Organizer: The 8th International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京
• [Presentation] 大腸癌におけるDNA修復因子FANCJ発現と5-FU感受性 (2012)
  • Author(s): 中西良太、北尾洋之、藤中良彦、安藤幸滋、佐伯浩司、大賀丈史、徳永えり子、沖英次、掛地吉弘、辻谷俊一、鴻江俊治、前原喜彦
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉市
• [Presentation] 胃癌におけるDNA ploidyと紡錘体形成チェックポイントタンパク質BUBR1の発現 (2012)
  • Author(s): 安藤幸滋、掛地吉弘、中西良太、久松雄一、北尾洋之、佐伯浩司、沖英次、大賀丈史、辻谷俊一、鴻江俊治、前原喜彦
  • Organizer: 第21回日本癌転移学会学術集会総会
  • Place of Presentation: 広島市
• [Presentation] Significance of mortalin expression in gastric cancer with normal p53 (2012)
  • Author(s): Ando K,. Oki E., Yan Z., Kitao H., Saeki H., Ohga T., Kakeji Y., Tujitani S., Kohnoe S., Maehara Y.
  • Organizer: ASCO GI
  • Place of Presentation: San Francisco
• [Presentation] Prognostic role of KRAS and BRAF mutations in Japanese patients with colorectal cancer. (2012)
  • Author(s): Oki E., Nakanishi R., Ando K., Saeki H., Ohga T., Kakeji Y., Tujitani S., Kohnoe S., Maehara Y.
  • Organizer: ASCO
  • Place of Presentation: Chicago
• [Presentation] FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer. (2012)
  • Author(s): Nakanishi R., Kitao H., Fujinaka Y., Yamashita N., Iimori M., Tokunaga E., Yamashita N., Morita M., Kakeji Y., Maehara Y.
  • Organizer: The 8th International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京
• [Presentation] 大腸癌におけるDNA修復因子FANCJの発現と5-FU感受性 (2012)
  • Author(s): 中西 良太、北尾 洋之、秋吉清百合、安藤 幸滋、佐伯 浩司、大賀 丈史、徳永えり子、沖 英次、掛地 吉弘、辻谷 俊一、鴻江 俊治、前原 喜彦
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
• [Presentation] 胃癌におけるDNA ploidyと紡錘体形成チェックポイントタンパク質BUBR1の発現 (2012)
  • Author(s): 安藤 幸滋、掛地 吉弘、中西 良太、久松 雄一、北尾 洋之、佐伯 浩司、沖 英次、大賀 丈史、辻谷 俊一、鴻江 俊治、前原 喜彦
  • Organizer: 第21回日本癌転移学会学術集会総会
  • Place of Presentation: 広島
• [Remarks]
  • URL: http://www.kyudai2geka.com/