Translational Research for cobinational chemotherapy with tumor microcirculation promotional agent in patients with advanced non-small cell lung cancer

• Project/Area Number: 23591133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: YASUDA Hiroyasu 東北大学, 大学院医学系研究科, 非常勤講師 (90396482)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 一酸化窒素供与剤 / 抗癌剤感受性 / 腫瘍直接浸潤 / 低酸素誘導因子 / 腫瘍組織内低酸素状態 / 無作為化比較試験 / ニトログリセリン / 非小細胞肺癌 / 一酸化窒素 / 腫瘍循環 / 化学療法感受性 / アムルビシン / ゲムシタビン / 腫瘍縮小効果 / がん細胞 / ペメトレキセド / RFC-1 / FPGS / 抗癌剤感受性増強効果 / 臨床試験

Research Abstract

Nitoroglycerin (NTG), nitric oxide donating agent (NDA), significantly reduced distribution of hypoxic area in solid cancer tissue in tumor bearing model mice. We made tumor bearing model mice with murine adenocarcinoma LLC cells and performed chemotherapy with them. Tumor growth curve was significantly inhibited in the group treated with pemetrexed and NTG compared with the group treated with pemetrexed alone.
Multicenter-phase II trial of 3rd line chemotherapy with amrubicin with NTG patch in patients with stage IIIB and IV non-small cell lung cancer was performed in Kyoto Univ., Tohoku Univ., Shinshu Univ., and Juntendo Univ. Now the data analysis has been performed, and will be published.

Research Products

• [Journal Article] Nitric oxide enhances pemetrexed cytotoxicity via NO-cGMP signaling in lung adenocarcinoma cells in vitro and in vivo (2013)
  • Author(s): Nagai H, Yasuda H, Hatachi Y, Xue D, Sasaki T, Yamaya M, Sakamori Y, Togashi Y, Masago K, Ito I, Kim YH, Mio T, Mishima M.
  • Journal Title: Int J Oncology Volume: 41 Pages: 3271-3278
  • DOI: 10.3892/ijo.2012.1461
  • Peer Reviewed
• [Journal Article] Use of glucose solution for the alleviation of gemcitabine-induced vascular pain: a double blind randomized crossover study. (2013)
  • Author(s): Nagai H, Kitano T, Nishimura T, Yasuda H, Nakata K, Takashima S, Kanai M, Matsumoto S, Mori Y, Kakudo Y, Sato H, Yamaguchi T, Kameno K, Kim YH, Mishima M, Yanagihara K.
  • Journal Title: Support Care Cancer Volume: 21 Issue: 12 Pages: 3271-3278
  • DOI: 10.1007/s00520-013-1901-9
  • Peer Reviewed
• [Journal Article] Nitric oxide enhances pemetrexed cytotoxicity via NO-cGMP signaling in lung adenocarcinoma cells in vitro and in vivo (2012)
  • Author(s): Nagai N, Yasuda H, Hatachi Y, et al.
  • Journal Title: Int J Oncology Volume: 未定
  • Peer Reviewed
• [Journal Article] L-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells (2012)
  • Author(s): Asada M, Yoshida M, Hatachi Y, et al.
  • Journal Title: Respir Physiol Neurobiol Volume: 180 Pages: 112-118
  • Peer Reviewed
• [Journal Article] Safty of erlotinib treatment in outpatients with previously treated non-small-cell lung cancer in Japan (2011)
  • Author(s): Nagai H, Tanaka S, Niimi M, et al.
  • Journal Title: Int J Clin Oncol Volume: 16 Pages: 560-567
  • Peer Reviewed
• [Journal Article] A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD (2011)
  • Author(s): Sasaki T, Nakayama K, Yasuda H, et al.
  • Journal Title: Ther Adv Respir Dis Volume: 5 Pages: 91-103
  • Peer Reviewed
• [Journal Article] Procaterol inhibits rhinovirus infection in primary cultures of human tracheal epithekial cells (2011)
  • Author(s): Yamaya M, Nishimura H, Hatachi Y, et al.
  • Journal Title: Eur J Pharmacol Volume: 650 Pages: 431-444
  • Peer Reviewed
• [Presentation] Nitric oxide may improve pemetrexed cytotoxicity in lung adenocarcinoma cells (2011)
  • Author(s): Hiroyasu Yasuda, Hiroki Nagai
  • Organizer: 16th World Congress on Advances in Oncology(招待講演)
  • Place of Presentation: Rhodes island, Greece
• [Remarks] 非小細胞肺癌に対するニトログリセリン併用アムルビシン化学療法の臨床試験
  • URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&type=summary&repcptno=R000000973&language=J
• [Remarks] 進行非小細胞肺癌に対するGTN+/-CBDCA・TXL化学療法の無作為化比較試験
  • URL: https://www.clinicaltrial.gov/ct2/show/record/NCT00616031?spons=%22Kyoto+University%22&spons_ex=Y&rank=5
• [Remarks] 非小細胞肺癌に対するニトログリセリン併用アムルビシン化学療法の臨床試験
  • URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000000973&language=J
• [Remarks] 進行非小細胞肺癌に対するGTN＋/－CBDCA・TXL化学療法の無作為化比較試験
  • URL: http://www.clinicaltrial.gov/ct2/show/record/NCT00616031?spons=%22Kyoto+University%22&spons_ex=Y&rank=5
• [Remarks] 非小細胞肺癌に対するニトログリセリン併用アムルビシン化学療法の臨床試験
  • URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000000973&language=J