Neuroendocrine differentiation from multipotent cancer stem cell in small cell lung cancer : elucidation of mechanisms and application to treatment

• Project/Area Number: 19590926
• 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 Aichi Cancer Center Research Institute, 分子腫瘍学部, 研究員 (30344336)
• Co-Investigator(Kenkyū-buntansha): OSADA Hirotaka 愛知県がんセンター(研究所), 分子腫癌学部, 室長 (30204176)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 小細胞肺癌 / 幹細胞 / 分化 / 転写因子

Research Abstract

EGFR-TKI長期投与した肺腺癌患者の経過中、原発の腺癌部に小細胞肺がんが発生。その切除標本の解析からEGFR遺伝子L858R変異を腺癌と小細胞肺癌に共通して認め、免疫染色検査で小細胞肺癌はEGFR遺伝子とNotch3遺伝子発現の消失とAsh1遺伝子発現陽性、腺癌は逆の染色パターンであった。肺癌幹細胞からの腺癌への分化と小細胞肺癌への分化を示す癌化過程を示す症例と考えられた。非小細胞肺癌の発ガンにおいてNotch-3は重要であるが、細胞株でRT-PCR法での発現とトポイソメラーゼII阻害剤の感受性との相関は見られなかった。

Research Products

• [Journal Article] Gefitinib for the treatment of non-small-cell lung cancer (2009)
  • Author(s): Hida T, Ogawa S, Park JC, Park JY, Shimizu J, Horio Y, Yoshida K
  • Journal Title: Expert Rev Anticancer Ther. 9 Pages: 17-35
• [Journal Article] mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity to cisplatin, carboplatin and gemcitabine in human lung cancer cell lines (2008)
  • Author(s): Shimizu J, Horio Y, Osada H, Hida T, Hasegawa Y, Shimokata K, Takahashi T, Sekido Y, Yatabe Y
  • Journal Title: Respirology 13 Pages: 510-517
• [Journal Article] YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation (2008)
  • Author(s): Yokoyama T, Osada H, Murakami H, Tatematsu Y, Taniguchi T, Kondo Y, Yatabe Y, Hasegawa Y, Shimokata K, Horio Y, Hida T, Sekido Y
  • Journal Title: Carcinogenesis 29 Pages: 2139-2146
• [Journal Article] Epidermal growth factor receptor mutations in small cell lung cancer (2008)
  • Author(s): Tatematsu A, Shimizu J, Murakami Y, Horio Y, Nakamura S, Hida T, Mitsudomi T, Yatabe Y
  • Journal Title: Clin Cancer Res. 14 Pages: 6092-6096
• [Journal Article] mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity of cisplatin, carboplatin and gemcitabine in human lung can cer cell lines (2008)
  • Author(s): J Shimizu, Y Horio, H Osada, et al.
  • Journal Title: Respirology 13 Pages: 510-517
  • Peer Reviewed
• [Journal Article] YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylation (2008)
  • Author(s): Yokoyama T, Osada H, Horio Y, Sekido Y
  • Journal Title: Carcinogenesis 29 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] Epidermal growth factor receptor mutations in small cell lung cancer (2008)
  • Author(s): Tatematsu A, Shimizu J, Murakami Y, Horio Y, ., Yatabe Y
  • Journal Title: Clin Cancer Res 14 Pages: 6092-6096
  • Peer Reviewed
• [Journal Article] Genomic pro filing of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32 (2007)
  • Author(s): Taniguchi T, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y
  • Journal Title: Cancer Sci. 98 Pages: 438-446
• [Journal Article] Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer (2007)
  • Author(s): Yoshida K, Yatabe Y, Park JY, Shimizu J, Horio Y, Matsuo K, Kosaka T, Mitsudomi T, Hida T
  • Journal Title: J Thorac Oncol. 2 Pages: 22-28
• [Journal Article] Chest wall dissemination of nocardiosis after percutaneous transthoracic needle biopsy (2007)
  • Author(s): Shimamoto H, Inaba Y, Yamaura H, Sato Y, Kamiya M, Miyazaki M, Arai Y, Horio Y
  • Journal Title: Cardiovasc Intervent Radiol. 30 Pages: 797-9
• [Journal Article] Disproportionate representation of KRAS gene mutation in atypical adenomatous hyperplasia, but even distribution of EGFR gene mutation from preinvasive to invasive adenocarcinomas (2007)
  • Author(s): Sakamoto H, Shimizu J, Horio Y, Ueda R, Takahashi T, Mitsudomi T, Yatabe Y
  • Journal Title: J Pathol 212 Pages: 287-94
• [Journal Article] mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity of cisplatin, carboplatin and gemcitabine in human lung cancer cell lines
  • Author(s): J Shimizu, Y Horio, H Osada, et. al.
  • Journal Title: Respirology (In press)
  • Peer Reviewed
• [Presentation] mRNA expression of RanBP2 is unlikely to be associated with chemosensitivity of amrubicine (topoisomerase II inhibitor) in human lung cancer cell lines (2008)
  • Author(s): YOSHITSUGU HORIO, JUNICHI SHIMIZU, HIROTAKA OSADA, TOYOAKI HIDA, YOSHITAKA SEKIDO
  • Organizer: 癌学会
• [Presentation] 小細胞肺癌におけるEGFR遺伝子変異の検討 (2007)
  • Author(s): 清水淳一、堀尾芳射, 他6人
  • Organizer: 肺癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-09
• [Presentation] mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity of cisplatin, carboplatin and gemcitabine in human lung cancer cell lines (2007)
  • Author(s): YOSHITSUGU HORIO, JUNICHI SHIMIZU, HIROTAKA OSADA, TOYOAKI HIDA, YOSHINORI HASEGAWA, KAORU SHIMOKATA, TAKASHI TAKAHASHI, YOSHITAKA SEKIDO, YASUSHI YATABE
  • Organizer: 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: San Francisco, California
• [Presentation] 小細胞肺癌におけるEGFR遺伝子変異の検討 (2007)
  • Author(s): 清水淳市, 堀尾芳嗣, 小川紫都, 朴智栄, 吉田公秀, 樋田豊明
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/