Development of novel therapy for malignant mesothelioma by controllingADCC activity.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tottori University
• Principal Investigator: SHIMIZU Eiji 鳥取大学, 医学部, 教授 (50187449)
• Co-Investigator(Kenkyū-buntansha): CHIKUMI Hiroki 鳥取大学, 医学部付属病院, 准教授 (90283994)
• Project Period (FY): 2010 – 2012
• Keywords: 胸膜中皮腫 / 分子標的治療

Research Abstract

Most patients with malignant pleural mesothelioma (MPM) have a history of exposure to carcinogenic asbestos fibers, and the latent period of this disease is more than 40 years. Therefore, the numbers of the patients are now still increasing. Cetuximab is a chimeric mouse-human antibody directed against the extracellular domain of EGFRand has been shown remarkable effects for colorectal cancer and head and neck cancer. However, no published in vitro or in vivo studies have focused on the effect of cetuximab against MPM. In the present study, we found that cetuximab has potent anti-tumor activity against MPM in combination with the methods to enhance its immunological function, antibody-dependent cellular cytotoxicity (ADCC) activity. Our data indicate the important role of ADCC activity in the mechanism of action of cetuximab and underscore the promising potential of cetuximab as a new class of therapeutic agent for use against MPM.

Research Products

• [Journal Article] Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity (2012)
  • Author(s): Takata M, Chikumi H, Miyake N, Adachi K, Kanamori Y, Yamasaki A, Igishi T, Burioka N, Nanba E, Shimizu E
  • Journal Title: Cancer Biol Ther Volume: 13 Pages: 369-378
  • URL: http://dx.doi.org/10.4161/cbt.19238
  • Peer Reviewed
• [Journal Article] Diagnostic and Prognostic Impact of Serum Soluble UL16-Binding Protein 2 in Lung Cancer Patients. (2012)
  • Author(s): Yamaguchi K, Chikumi H, Shimizu A, Takata M, Kinoshita N, Hashimoto K, Nakamoto M, Matsunaga S, Kurai J, Miyake N, Matsumoto S, Watanabe M, Yamasaki A, Igishi T, Burioka N, Shimizu E
  • Journal Title: Cancer Science Volume: 103 Pages: 1405-1413
  • DOI: DOI:10.1111/j.1349-7006.2012.02330.x
  • Peer Reviewed
• [Journal Article] Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells (2012)
  • Author(s): Miyake N, Chikumi H, Takata M, Nakamoto M, Igishi T, Shimizu E
  • Journal Title: Oncology reports 28 Volume: 28 Pages: 848-854
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22313637
  • Peer Reviewed
• [Journal Article] Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma (2012)
  • Author(s): Kurai J, Chikumi HT, Hamada H, Yano S, , Hashimoto K, Takata M, Sako T, Yamaguchi K, Kinoshita N, Watanabe M, Touge H, Makino H, Igishi Shimizu E
  • Journal Title: International Journal of Oncology Volume: 41 Pages: 1610-1618
  • DOI: DOI:10.3892/ijo.2012.1607
  • Peer Reviewed
• [Presentation] Circulating serum ULBP2 in patients with various lung diseases (2012)
  • Author(s): Kinoshita N, Chikumi H, Yamaguchi K, Takata M, Nakamoto M, Kodani M, Matsumoto S, Kawasaki Y, Tadashi I, Shimizu E
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸コンベンションセンター(神戸)
  • Year and Date: 2012-04-22
• [Presentation] Development of a novel combination therapy using cetuximab (2012)
  • Author(s): Takata M, Chikumi H, Igishi T, Burioka N, Yamasaki A, Nakamoto M, Kinoshita N, Kitaura T, Okada K, Shimizu E
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸コンベンションセンター(神戸)
  • Year and Date: 2012-04-20
• [Presentation] Antibody-dependent cellular cytotoxicity mediated by cetuximab against mesothelioma cells (2010)
  • Author(s): Chikumi H, Kurai J, Kinoshita N, Nakamoto M, Matsumoto S, Igishi T, Hamada H, Yano S, Shimizu E
  • Organizer: The 10th international conference of the international mesothelioma interest group
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-09-02