Construction of the system for lung cancer treatment based onmethylation profile and EGFR mutation

• Project/Area Number: 19591614
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: MURAKAWA Tomohiro The University of Tokyo, 医学部・附属病院, 助教 (50359626)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Jun 東京大学, 医学部・附属病院, 准教授 (90188954) ; FUKAMI Takeshi 東京大学, 医学部・附属病院, 助教 (40396742) ; TAKAI Daiya 東京大学, 医学部・附属病院, 講師 (90361493)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 呼吸器外科学 / 癌 / ゲノム / 外科 / 遺伝子

Research Abstract

発癌の一因に遺伝子のメチル化による不活化があり、肺癌でも複数の遺伝子でメチル化の報告がなされている。従来肺癌でメチル化の報告がなかった遺伝子を新たに検索するため、バイオインフォマティクス並びに実験的手法の両方をうまく用いることで、肺癌でメチル化の存在する遺伝子を新たに8つ同定した。これらの遺伝子の1つであるGOS2遺伝子のメチル化が非扁平上皮癌と比較して扁平上皮癌において有意に多いことが判明した。また従来から報告があったp16遺伝子のメチル化とEGFR遺伝子変異の排他性も我々のデータから確認された。

Research Products

• [Journal Article] Chest wall desmoid tumor with life-threatening intrathoracic extension. (2009)
  • Author(s): Murakawa T, Fpkami T, Nakajim a J, Takamoto S.
  • Journal Title: Eur J Cardiothorac Surg. 38 Pages: 538-538
  • Peer Reviewed
• [Journal Article] Video-assisted thoracic surgery lobectomy preserves more latissimus dorsi muscle than conventional surgery. (2009)
  • Author(s): Karasaki T, Nakajima J, Murakawa T, Fukami T, Yoshida Y, Kusakabe M, Ohtsu H, Takamoto S.
  • Journal Title: Interact Cardiovasc Thorac Surg. 8 Pages: 316-9
  • Peer Reviewed
• [Journal Article] Mucinous adenocarcinoma of the thymus: A distinct variant of thymic car cinoma. (2009)
  • Author(s): Maeda D, Ota S, Ikeda S, Kawano R, Hata E, Nakajima J, Mori M, Fukayama M.
  • Journal Title: Lung Cancer. 64 Pages: 22-7
  • Peer Reviewed
• [Journal Article] Active specific immunotherapy and cell-transfer therapy for the treatment of non-small cell lung cancer. (2008)
  • Author(s): Kakimi K, Nakajima J, Wada H.
  • Journal Title: Lung Cancer. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Zoledronate facilitates large-scale ex vivo expansion of functional gamma delta T cells from cancer patients for use in adoptive immunotherapy. (2008)
  • Author(s): Kondo M, Sakuta K, Noguchi A, Ariyoshi N, Sato K, Sato S, Sato K, Hosoi A, Nakajima J, Yoshida Y, Shiraishi K, Nakagawa K, Kakimi K.
  • Journal Title: Cytotherapy. 10 Pages: 842-56
  • Peer Reviewed
• [Journal Article] Disease-free interval length correlates to prognosis of patients who under went metastasectomy for esophageal lung metastases. (2008)
  • Author(s): Shiono S, Kawamura M, Sato T, Nakagawa K, Nakajima J, Yoshino I, Ikeda N, Horio H, Akiyama H, Kobayashi K; Metastatic Lung Tumor Study Group of Japan.
  • Journal Title: J Thorac Oncol. 3 Pages: 1046-9
  • Peer Reviewed
• [Journal Article] Postthymectomy myasthenia gravis: relationship with thymoma and antiac etylcholine receptor antibody. (2008)
  • Author(s): Nakajima J, Murakawa T, Fukami T, Sano A, Takamoto S, Ohtsu H.
  • Journal Title: Ann Thorac Surg. 86 Pages: 941-5
  • Peer Reviewed
• [Journal Article] Surgical outcomes for pulmonary metastases from hepatocellular carcinoma. (2008)
  • Author(s): Kawamura M, Nakajima J, Matsuguma H, Horio H, Miyoshi S, Nakagawa K, Fujisawa T, Kobayashi K; Metastatic Lung Tumor Study Group of Japan.
  • Journal Title: Eur J Cardiothorac Surg. 34 Pages: 196-9
  • Peer Reviewed
• [Journal Article] Is thoracoscopic surgery justified to treat pulmonary metastasis from colorectal cancer? (2008)
  • Author(s): Nakajima J, Murakawa T, Fukami T, Takamoto S.
  • Journal Title: Interact Cardiovasc Thorac Surg. 7 Pages: 212-6
  • Peer Reviewed
• [Journal Article] A second-generation profilingsystem for quantitative methylationanalysis of multiple gene promoters : application to lung cancer (2007)
  • Author(s): Sano A, Kage H, Sugimoto K, Kitagawa H, Aki N, Goto A, Fukayama M, Nakajima J, akamoto S, Nagase T, Yatomi Y, Ohishi N, Takai D
  • Journal Title: Oncogene 26(45) Pages: 6518-25
  • Peer Reviewed
• [Journal Article] A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer. (2007)
  • Author(s): Sano A, Kage H, Sugimoto K, Kitagawa H, Aki N, Goto A, Fukayama M, Nakajima J, Takamoto S, Nagase T, Yatomi Y, Ohishi N, Takai D.
  • Journal Title: Oncogene 26 Pages: 6518-25
  • Peer Reviewed
• [Journal Article] The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus. (2007)
  • Author(s): Sugimoto K, Kage H, Aki N, Sano A, Kitagawa H, Nagase T, Yatomi Y, Ohishi N, Takai D.
  • Journal Title: Biochem Biophys Res Commun 359 Pages: 497-502
  • Peer Reviewed
• [Journal Article] Hypoxia increases the motility of lung adenocarcinoma cell line A549 via activation of the epidermal growth factor receptor pathway. (2007)
  • Author(s): Wang T, Niki T, Goto A, Ota S, Morikawa T, Nakamura Y, Ohara E, Ishikawa S, Aburatani H, Nakajima J, Fukayama M.
  • Journal Title: Cancer Sci 98 Pages: 506-11
  • Peer Reviewed
• [Journal Article] c-Met activation in lung adenocarcinoma tissues: animmunohistochemical analysis. (2007)
  • Author(s): Nakamura Y, Niki T, Goto A, Morikawa T, Miyazawa K, Nakajima J, Fukayama M.
  • Journal Title: Cancer Sci 98 Pages: 1006-13
  • Peer Reviewed
• [Journal Article] Invasive lymphangioma of the lung manifesting as a large pulmonary mass with hemoptysis: report of a case. (2007)
  • Author(s): Nakajima J, Goto A, Takamoto S, Murakawa T, Fukami T, Kusakabe M.
  • Journal Title: Surg Today 37 Pages: 418-22
  • NAID: 10020150150
  • Peer Reviewed
• [Journal Article] Pulmonary intimal sarcoma treated by a left pneumonectomy with pulmonary arterioplasty under cardiopulmonary bypass: report of a case. (2007)
  • Author(s): Nakajima J, Morota T, Matsumoto J, Takazawa Y, Murakawa T, Fukami T, Yamamoto T, Takamoto S.
  • Journal Title: Surg Today 37 Pages: 496-9
  • NAID: 10019492344
  • Peer Reviewed
• [Journal Article] Posterior mediastinal hemangioma successfully resected with cardiopulmonary bypass; report of a case (2007)
  • Author(s): Sugiura M, Nakajima J, Morota T, Yamamoto T, Sano A, Fukami T, Murakawa T, Ota S, Takamoto S.
  • Journal Title: Kyobu Geka 60 Pages: 857-60
  • NAID: 40015580948
  • Peer Reviewed
• [Journal Article] Is finger palpation at operation indispensable for pulmonary metastasectomy in colorectal cancer? (2007)
  • Author(s): Nakajima J, Murakawa T, Fukami T, Sano A, Sugiura M, Takamoto S.
  • Journal Title: Ann Thorac Surg 84 Pages: 1680-4
  • Peer Reviewed
• [Journal Article] Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis (2007)
  • Author(s): Babu AN, Murakawa, T, Thurman JM, Miller EJ, Henson PM, Zamora MR, Voelkel NF, Nicolls MR
  • Journal Title: The Journal of Clinical Investigation 117 Pages: 3774-3785
  • Peer Reviewed
• [Journal Article] 胸腔鏡補助下に摘出した気管分岐部Castleman病の1例 (2007)
  • Author(s): 真船健一, 本郷久美子, 下山省二, 中島淳, 高澤豊, 上西紀夫
  • Journal Title: 日本外科系連合学会誌 32 Pages: 648-653
  • NAID: 10020112977
  • Peer Reviewed
• [Journal Article] 【セカンドオピニオン実践ガイド 実地診療にも役立つ病期・病態別治療指針】主要疾患の病期・病態別治療法 肺癌。 (2007)
  • Author(s): 中島 淳
  • Journal Title: Medical Practice 24 Pages: 118-124
  • Peer Reviewed
• [Presentation] Novel approach to identify methylated genes in non-small cell lung cancer and analyses of methylation profile. (2008)
  • Author(s): Kusakabe M, Takai D et al.
  • Organizer: 67th Annual Meeting of the Japanese Cancer A ssociation
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2008-10-29
• [Presentation] Knockdown of Tgf131 with Replication-Defective Serotype 2/5 Adeno-Associated Virus Carrying Short Hairpin RNA. (2008)
  • Author(s): Kage H, Takai D et al.
  • Organizer: 48th Annual Meeting of the Japanese Respiratory Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2008-06-16
• [Presentation] Functional Analysis of PIWIL4 in the induction of H3K9 Methylation at the pl6Ink4a Locus. (2008)
  • Author(s): Aki N, Takai D et al.
  • Organizer: American Association for Cancer Research Special Conference on Cancer Research Cancer Epigenetics
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2008-05-30
• [Presentation] Novel Approach to Identify Methylated. Genes in Non-small Cell Lung Cancer and Methylation of GOS2 as Possible Biomarker of Squamous Lung Cancer. (2008)
  • Author(s): Kusakabe M, Takai D et al.
  • Organizer: American Association for Cancer Research Special Conference on Cancer Research Cancer Epigenetics
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2008-05-29
• [Presentation] Novel approach to identify aberrantlymethylated genes in non-small cell lungcancer and methylation of G0S2 as possiblebiomarker of squamous lung cancer (2008)
  • Author(s): Kusakabe M, Kutomi T, Aki N, Kage H, Sano A, Hamano E, Kitagawa H, Murakawa T, Nakajima J, Takamoto S, Ohishi N, NagaseT, Ohta S, Fukayama M, Yatomi Y, Takai D
  • Organizer: American Association for Cacner Research Cancer Epigenetics
  • Place of Presentation: Boston, MA, USA.
• [Presentation] The Induction of H3K9 Methylation by PIWIL4 at the p16^<Ink4a> Iocus (2007)
  • Author(s): Aki N, Sugimoto K, Kage H, Sano A, Kutomi T, Kusakabe M, Kitagawa H, Nagase T, Yatomi Y, Ohishi N, Takai D.
  • Organizer: An AACR Special Conference in Cancer Research The Role of Non-Coding RNAs in Cancer
  • Place of Presentation: Hyatt Regency Cambridge Cambridge, Massachusetts
  • Year and Date: 2007-11-01
• [Presentation] Knockdown of TgffA1 with Serotype 2/5 Hybrid Adeno-Associated Virus Carrying Short Hairpin RNA (2007)
  • Author(s): Kage H, Kutomi T, Kusakabe M, Aki N, Kitagawa H, Ohishi N, Nagase T, Takai D.
  • Organizer: An AACR Special Conference in Cancer Research The Role of Non-Coding RNAs in Cancer
  • Place of Presentation: Hyatt Regency Cambridge Cambridge, Massachusetts
  • Year and Date: 2007-11-01
• [Presentation] Functional microcirculation is lost in airway fibrosis. (2007)
  • Author(s): Babu AN, Murakawa T, Voelkel NF, Zamora MR, Henson P, Nicolls MR
  • Organizer: Thomas L. Petty Aspen Lung Conference 2007 Annual Meeting
  • Place of Presentation: Aspen CO, USA
  • Year and Date: 2007-06-08
• [Presentation] A new model of airway transplantation to evaluate early inflammatory events, fibroproliferation and epithelial mesenchymal transformation (EMT) (2007)
  • Author(s): Babu AN, Murakawa T, Zamora MR, Grower F, Kerklo M, Nicolls MR
  • Organizer: Thomas L. Petty Aspen Lung Conference 2007 Annual Meeting
  • Place of Presentation: Aspen CO, USA
  • Year and Date: 2007-06-07
• [Presentation] 左室駆出率低下症例に対する肺癌手術の検討 (2007)
  • Author(s): 村川知弘、中島淳、深見武史、佐野厚、日下部将史、杉浦未紀、高本眞一
  • Organizer: 第24回日本呼吸器外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-05-17
• [Presentation] 完全内臓逆位に合併した原発性肺癌の1手術例 (2007)
  • Author(s): 村川知弘、深見武史、日下部将史、杉浦未紀、佐野厚、中島淳、高本眞一
  • Organizer: 第24回日本呼吸器外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-05-17
• [Presentation] Distinction between doubleprimary lung cancer and intrapulmonarymetastasis using a system for profilingthe DNA methylation status of multiplegene promoters (2007)
  • Author(s): Sano A, Kage H, Sugimoto K, Kitagawa H, Aki N, Goto A, Fukayama M, Nakajima J,Takamoto S, Nagase T, Yatomi Y, Ohishi N,Takai D.
  • Organizer: American Association for Cancer Research Annual Meeting 2007
  • Place of Presentation: Boston, MA, USA.
• [Book] 実験医学別冊注目のバイオ実験シリーズニエピジェネティクス実験プロトコールー(分担) (2008)
  • Author(s): 牛島俊和、 眞貝洋一編
  • Total Pages: 267
  • Publisher: 羊土社
• [Book] MOOK肺癌の臨床2007-2008 (2007)
  • Author(s): 中島 淳
  • Total Pages: 8
  • Publisher: 篠原出版・東京
• [Remarks]
  • URL: http://kokyuki.umin.jp/305.html
• [Remarks]
  • URL: http://kokyuki.umin.jp/305.html