Development of treatment strategies aimed at nucleocytoplasmic shuttling for small cell lung cancer

• Project/Area Number: 21591013
• 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: Aichi Cancer Center Research Institute
• Principal Investigator: HORIO Yoshitsugu 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (30344336)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小細胞肺癌 / 核細胞質間シャトル / p27

Research Abstract

Cell cycle regulator p27 shuttles between the nucleus and the cytoplasm. Phosphorylation at threonine 198(T198) and 157(T157) increase cell motility. We showed S10 hosphorylation was associated with T198 and T157 phosphorylation in small cell lung cancer(SCLC) cell lines. In 30 surgically resected SCLC specimens, however, immunohistochemistry revealed high expression of phosphorylated p27 at T198 and T157. Leptomycin B or knockdown of cellular CRM1 by siRNA showed additive effects with topoisomerase II inhibitors(Etoposide and Amrubicine) in SCLC cell lines and a fibroblast cell line. There were no correlations between chemosensitivity of amrubicin and mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes.

Research Products

• [Journal Article] Patterns of recurrence and outcome in patients with surgically resected small cell lung cancer (2011)
  • Author(s): Ogawa S、Horio Y、Yatabe Y、Fukui T、Ito S、Hasegawa Y、Mitsudomi T、Hida T.
  • Journal Title: Int J Clin Oncol
  • NAID: 10030951466
  • Peer Reviewed
• [Journal Article] Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines (2010)
  • Author(s): Horio Y、Osada H、Shimizu J、Ogawa S、Hida T、Sekido Y.
  • Journal Title: Cancer Chemother Pharmacol Volume: 66 Pages: 237-243
  • Peer Reviewed
• [Journal Article] Clinical outcomes of advanced non-small cell lung cancer patients screened for epidermal growth factor receptor gene mutations (2010)
  • Author(s): Yoshida K、Yatabe Y、Park J、Ogawa S、Park JY、Shimizu J、Horio Y、Matsuo K、Mitsudomi T、Hida T
  • Journal Title: J Cancer Res Clin Oncol Volume: 36 Pages: 525-537
  • Peer Reviewed
• [Journal Article] Clinical outcomes of advanced non-small cell lung cancer patients screened for epidermal growth factor receptor gene mutations (2010)
  • Author(s): Yoshida K
  • Journal Title: J Cancer Res Clin Oncol. 36 Pages: 527-535
  • Peer Reviewed
• [Journal Article] Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells (2009)
  • Author(s): Kawaguchi K、Murakami H、Taniguchi T、Fujii M、Kawata S、Fukui T、Kondo Y、Osada H、Usami N、Yokoi K、Ueda Y、Yatabe Y、Ito M、Horio Y、Hida T、Sekido Y.
  • Journal Title: Carcinogenesis Volume: 30 Pages: 1097-1105
  • Peer Reviewed
• [Journal Article] Relationship of mRNA expressions of RanBP2 and topoisomerase ll isoforms to cytotoxicity of amrubicin in human lung cancer cell lines (2009)
  • Author(s): Horio Y
  • Journal Title: Cancer Chemother Pharmacol Oct 7(Epub)
  • Peer Reviewed
• [Journal Article] Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells (2009)
  • Author(s): Kawaguchi K
  • Journal Title: Carcinogenesis 30 Pages: 1097-1105
  • Peer Reviewed
• [Presentation] Clinical features in surgically treated patients with small cell lung cancer : Risk of brain metastasis and possible role of prophylactic cranial irradiation (2010)
  • Author(s): Horio Y、Ishikawa S、Yatabe Y、Shimizu J、Yoshida K、Fukui T、Ito S、Hasegawa Y、Mitsudomi T、Hida T
  • Organizer: ASCO
• [Presentation] 肺癌細胞株におけるトポイソメラーゼII阻害剤アムルビシンの感受性とRanBP2とトポイソメラーゼII遺伝子発現 (2009)
  • Author(s): 堀尾芳嗣、清水淳市、朴智栄、朴将哲、小川紫都、吉田公秀、樋田豊明、関戸好孝
  • Organizer: 第49回日本呼吸器学会
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/