肺がんにおける染色体不安定化と臨床・病理学的特徴，抗がん剤感受性の関連の検討

• 研究課題/領域番号: 24659267
• 研究種目: 挑戦的萌芽研究
• 配分区分: 補助金
• 研究分野: 病態検査学
• 研究機関: 東京大学
• 研究代表者: 高井 大哉 東京大学, 医学部附属病院, 講師 (90361493)
• 研究期間 (年度): 2012-04-01 – 2014-03-31
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 3,900千円 (直接経費: 3,000千円、間接経費: 900千円); 2013年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円); 2012年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
• キーワード: 肺がん / ３'非翻訳領域 / マイクロＲＮＡ / 腫瘍検査学 / 発現制御

研究概要

当初予定した遺伝子ついて肺がん細胞株18株で突然変異が見られなかったため，研究対象を変更した．mRNAの3’非翻訳領域(3'UTR)はマイクロRNAが結合することにより翻訳の調節を行う転写後発現調節に関係していることが近年明らかにされている．また，様々ながんでマイクロRNAの発現異常と，がん化やがんの性質が変わることも報告されている．最近がんにおいてmRNAの短縮が起きることが報告され，またmRNAの3'UTRを安定させる分子も報告された．そこでわれわれは肺がんにおいて短縮する遺伝子を検索し，10個の遺伝子を用いて，3'UTRの短縮が起きると，肺がんの術後再発の頻度が増えることを明らかにした．

研究成果

• [雑誌論文] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked (2014)
  • 著者名/発表者名: Yoshida Y, Ota S, Murakawa T, Takai D
  • 雑誌名: Annals of Thoracic and Cardiovascular Surgery 巻: 20 号: Supplement ページ: 582-584
  • DOI: 10.5761/atcs.cr.12.02217
  • NAID: 130003377861
  • ISSN: 1341-1098, 2186-1005
  • 査読あり
• [雑誌論文] Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model (2013)
  • 著者名/発表者名: Yamauchi H, Motomura N, Chung UI, Sata M, Takai D, Saito A, Ono M, Takamoto S.
  • 雑誌名: J Thorac Car diovasc Surg 巻: 145(2) ページ: 522-530
• [雑誌論文] Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer (2013)
  • 著者名/発表者名: Takahara N, Nakai Y, Isayama H, Sasaki T, Satoh Y, Takai D, Hamada T, Uchino R, Mizuno S, Miyabayashi K, Mohri D, Kawakubo K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tada M, Yatomi Y, Koike K.
  • 雑誌名: Cancer Chemother Pharmacol 巻: 71(1) ページ: 85-92
• [雑誌論文] High-grade lung adenocarcinoma with fetal-lung-like morphology–Clinicopathological, immunohistochemical, and molecular analyses of 17 cases (2013)
  • 著者名/発表者名: Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
  • 雑誌名: Amer ican J of Sur g. Pathology 巻: 37(6) ページ: 924-932
• [雑誌論文] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer (2013)
  • 著者名/発表者名: Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D.
  • 雑誌名: Int J Clin Exp Pathol 巻: 6(4) ページ: 598-612
• [雑誌論文] A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer (2013)
  • 著者名/発表者名: Sasaki T, Isayama H, Nakai Y, Takahara N, Satoh Y, Takai D, Kogure H, Yamamoto N, Hirano K, Tada M, Yatomi Y, Koike K.
  • 雑誌名: Anticancer Res 巻: 33(6) ページ: 2619-2622
• [雑誌論文] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked (2013)
  • 著者名/発表者名: Yoshida Y, Ota S, Murakawa T, Takai D, Nakajima J.
  • 雑誌名: Ann Thorac Cardiovasc Sur g 巻: (Epub ahead)
  • NAID: 130003377861
• [雑誌論文] Detection of novel paraja ring finger 2-fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non-small cell lung cancer (2013)
  • 著者名/発表者名: Kawakami M, Ishikawa R, Amano Y, Sunohara M, Watanabe K, Ohishi N, Yatomi Y, Nakajima J, Fukayama M, Nagase T, Takai D.
  • 雑誌名: Cancer Sci 巻: 104(11) ページ: 1447-1454
• [雑誌論文] Successful Treatment of Mediastinal Unicentric Castleman's Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization (2013)
  • 著者名/発表者名: Amano Y, Takai D, Ohishi N, Shinozaki-Ushiku A, Fukayama M, Akahane M, Nakajima J, Nagase T.
  • 雑誌名: Case Rep Med ページ: 354507-354507
• [雑誌論文] Disruption of the expression and function of microRNAs in lung cancer as a result of epigenetic changes (2013)
  • 著者名/発表者名: Watanabe K & Takai D.
  • 雑誌名: Frontier s in Genetics 巻: 4 ページ: 275-275
• [雑誌論文] Disruption of the expression and function of microRNAs in lung cancer as a result of epigenetic changes. (2013)
  • 著者名/発表者名: Watanabe K, Takai D.
  • 雑誌名: Frontiers in Genetics 巻: 4 ページ: 275-275
  • 査読あり
• [雑誌論文] Successful Treatment of Mediastinal Unicentric Castleman's Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization. (2013)
  • 著者名/発表者名: Amano Y, Takai D, Ohishi N, Shinozaki-Ushiku A, Fukayama M, Akahane M, Nakajima J, Nagase T.
  • 雑誌名: Case Reports in Medicine 巻: 2013 ページ: 354507-354507
  • DOI: 10.1155/2013/354507
  • 査読あり
• [雑誌論文] Detection of novel paraja ring finger 2-fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non-small cell lung cancer. (2013)
  • 著者名/発表者名: Kawakami M, Ishikawa R, Amano Y, Sunohara M, Watanabe K, Ohishi N, Yatomi Y, Nakajima J, Fukayama M, Nagase T, Takai D.
  • 雑誌名: Cancer Sci 巻: 104 号: 11 ページ: 1447-1454
  • DOI: 10.1111/cas.12250
  • 査読あり
• [雑誌論文] A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer. (2013)
  • 著者名/発表者名: Sasaki T, Isayama H, Nakai Y, Takahara N, Satoh Y, Takai D, Kogure H, Yamamoto N, Hirano K, Tada M, Yatomi Y, Koike K.
  • 雑誌名: Anticancer Research 巻: 33 ページ: 2619-2622
  • 査読あり
• [雑誌論文] High-grade Lung Adenocarcinoma With Fetal Lung-like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases (2013)
  • 著者名/発表者名: Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
  • 雑誌名: Am J Surg Pathol 巻: 37(6) 号: 6 ページ: 924-932
  • DOI: 10.1097/pas.0b013e31827e1e83
  • 査読あり
• [雑誌論文] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer. (2013)
  • 著者名/発表者名: Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D.
  • 雑誌名: International Journal of Clinical & Experimental Pathology 巻: 6 ページ: 598-612
  • 査読あり
• [雑誌論文] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked. (2013)
  • 著者名/発表者名: Yoshida Y, Ota S, Murakawa T, Takai D, Nakajima J.
  • 雑誌名: Annals of Thoracic and Cardiovascular Surgery 巻: Epub ahead
  • NAID: 130003377861
  • 査読あり
• [雑誌論文] Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model. (2013)
  • 著者名/発表者名: Yamauchi Haruo
  • 雑誌名: The Journal of Thoracic and Cardiovascular Surgery 巻: 145 号: 2 ページ: 522-530
  • DOI: 10.1016/j.jtcvs.2012.03.010
  • 査読あり
• [雑誌論文] Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer (2013)
  • 著者名/発表者名: Takahara N, Nakai Y, Isayama H, Sasaki T, Satoh Y, Takai D, Miyabayashi K, Mohri D, Kawakubo K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tada M, Yatomi Y, Koike K
  • 雑誌名: Cancer Chemotherapy and Pharmacology 巻: 71 号: 1 ページ: 85-92
  • DOI: 10.1007/s00280-012-1981-0
  • 査読あり
• [雑誌論文] High-grade lung adenocarcinoma with fetal-lung-like morphology ? Clinicopathological, immunohistochemical, and molecular analyses of 17 cases (2013)
  • 著者名/発表者名: Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H
  • 雑誌名: American Journal of Surgical Pathology 巻: in press
  • 査読あり
• [雑誌論文] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in nonsmall cell lung cancer (2013)
  • 著者名/発表者名: Masanori Kawakami, Shigeki Morita, Mitsuhiro Sunohara, Yosuke Amano, Rie Ishikawa, Kousuke Watanabe, Emi Hamano, Nobuya Ohishi,Yutaka Yatomi, Takahide Nagase, Masashi Fukayama, Daiya Takai
  • 雑誌名: International Journal of Clinical and Experimental Pathology 巻: 6 ページ: 598-612
  • 査読あり
• [雑誌論文] Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer (2012)
  • 著者名/発表者名: Watanabe K, Emoto N, Hamano E, Sunohara M, Kawakami M, Kage H, Kitano K, Nakajima J, Goto A, Fukayama M, Nagase T, Yatomi Y, Ohishi N, Takai D.
  • 雑誌名: Int J Cancer 巻: 130(11) ページ: 2580-2590
• [雑誌論文] Pulmonary Venous Invasion, Determined by Chest Computed Tomographic Scan, as a Potential Early Indicator of Zygomycosis Infection : A Case Series (2012)
  • 著者名/発表者名: Kitagawa H, Watanabe K, Kage H, Inoh S, Goto A, Fukayama M, Nagase T, Ohishi N, Takai D.
  • 雑誌名: J Thorac Imaging 巻: 27(4)
• [雑誌論文] Analysis for the combination expression of CK20, FABP1 and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • 著者名/発表者名: Satoh Y, Mori K, Kitano K, Kitayama J, Yokota H, Sasaki H, Uozaki H, Fukayama M, Seto Y, Nagawa H, Yatomi Y, Takai D.
  • 雑誌名: J pn J Clin Oncol 巻: 42(2) ページ: 148-152
• [雑誌論文] Genome structure-based screening identifiedepigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. (2012)
  • 著者名/発表者名: Watanabe K, Goto A, Takai D.
  • 雑誌名: Int J Cancer. 巻: 130 号: 11 ページ: 2580-2590
  • DOI: 10.1002/ijc.26254
  • 査読あり
• [雑誌論文] Pulmonary Venous Invasion, Determined by Chest Computed Tomographic Scan, as a Potential Early Indicator of Zygomycosis Infection: A Case Series (2012)
  • 著者名/発表者名: Kitagawa H, Watanabe K, Kage H, Inoh S, Goto A, Fukayama M, Nagase T, Ohishi N, Takai D
  • 雑誌名: J Thorac Imaging 巻: 27 号: 4 ページ: W97-W99
  • DOI: 10.1097/rti.0b013e3182282d17
  • 査読あり
• [雑誌論文] Analysis for the combination expression of CK20, FABP1 and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • 著者名/発表者名: Satoh Y, Mori K, Kitano K, Kitayama J, Yokota H, Sasaki H, Uozaki H, Fukayama M, Seto Y, Nagawa H, Yatomi Y, Takai D
  • 雑誌名: Jpnease Journal of Clinical Oncology 巻: 42 号: 2 ページ: 148-152
  • DOI: 10.1093/jjco/hyr179
  • 査読あり
• [学会発表] Loss of PABPN1 and alternative polyadenylation yield poor prognosis in non-small cell lung cancer (2014)
  • 著者名/発表者名: Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D.
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Can lung cancer with overexpression of RET-proto oncogene be a good candidate for vandetanib treatment? (2014)
  • 著者名/発表者名: Sunohara M, Morita S, Kawakami M, Watanabe K, Kage H, Amano Y, Ishikawa R, Fukayama M, Nagase T, Ohishi N, Takai D.
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Histone methylation-mediated silencing of mir-139 enhances an aggressive phenotype of non-small cell lung cancer (2014)
  • 著者名/発表者名: Watanabe K, Sunohara M, Amano Y, Ishikawa R, Ichinose J, Nakajima J, Fukayama M, Yatomi Y, Nagase T, Ohishi N, Takai D.
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Loss of PABPN1 and alternative polyadenylation yield poor prognosis in non-small cell lung cancer. (2014)
  • 著者名/発表者名: Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Can lung cancer with overexpression of RET-proto oncogene be a good candidate for vandetanib treatment ? (2014)
  • 著者名/発表者名: Sunohara M, Morita S, Kawakami M, Watanabe K, Kage H, Amano Y, Ishikawa R, Fukayama M, Nagase T, Ohishi N, Takai D
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Histone methylation-mediated silencing of mir-139 enhances an aggressive phenotype of non-small cell lung cancer. (2014)
  • 著者名/発表者名: Watanabe K, Sunohara M, Amano Y, Ishikawa R, Ichinose J, Nakajima J, Fukayama M, Yatomi Y, Nagase T, Ohishi N, Takai D
  • 学会等名: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • 発表場所: San Diego, CA, USA
• [学会発表] Vandetanib Can Overcome the Acquired Resistance to Gefitinib Due to RET Overexpression in Lung Cancer (2012)
  • 著者名/発表者名: Sunohara M, Kawakami K, Watanabe K, Morita S, Kage H, Amano Y , Fukayama M, Nagase T, N. Ohishi N, Takai D.
  • 学会等名: The 24th EORTC-NCI-AACR Symposium on'Molecular Targets and Cancer Therapeutics'
  • 発表場所: Dublin, Island
• [学会発表] Identification of FER as a New Molecular Target in Non-small Cell Lung Cancer (2012)
  • 著者名/発表者名: Kawakami M, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nagase T, Yatomi Y, Takai D.
  • 学会等名: The 24th EORTC-NCI- AACR Symposium on'Molecular Targets and Cancer Therapeutics'
  • 発表場所: Dublin, Island
• [学会発表] Vandetanib Can Overcome the Aquired Resistance to Gefitinib Due to RET Overexpression in Lung Cancer (2012)
  • 著者名/発表者名: M. Sunohara, M. Kawakami, K. Watanabe, S. Morita, H. Kage, Y. Amano, M. Fukayama, T. Nagase, N. Ohishi, D. Takai
  • 学会等名: The 24th EORTC-NCI-AACR Symposium on ‘Molecular Targets and Cancer Therapeutics'
  • 発表場所: Dublin, Ireland
• [学会発表] Identification of FER as a New Molecular Target in Non-small Cell Lung Cancer (2012)
  • 著者名/発表者名: M. Kawakami, M. Sunohara, Y. Amano, R. Ishikawa, K. Watanabe, E. Hamano, N. Ohishi, T. Nagase, Y. Yatomi, D. Takai
  • 学会等名: The 24th EORTC-NCI-AACR Symposium on ‘Molecular Targets and Cancer Therapeutics'
  • 発表場所: Dublin, Ireland
• [備考]
  • URL: http://kokyuki.umin.jp/305.html