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Involvement of Akt/mTOR in lung cancer and design of novel therapy targeting them

Research Project

Project/Area Number 26460438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionJichi Medical University

Principal Investigator

DOBASHI Yoh  自治医科大学, 医学部, 准教授 (90231456)

Co-Investigator(Kenkyū-buntansha) 北川 雅敏  浜松医科大学, 医学部, 教授 (50294971)
坪地 宏嘉  自治医科大学, 医学部, 教授 (50406055)
後藤 明輝  秋田大学, 医学(系)研究科(研究院), 教授 (90317090)
Co-Investigator(Renkei-kenkyūsha) OOI Akishi  金沢大学, 医学部, 教授 (50160411)
SUGIMURA Haruhiko  浜松医科大学, 医学部, 教授 (00196742)
MATSUBARA Hirochika  山梨大学, 医学部, 講師 (00374166)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords肺癌 / Akt / 遺伝子増幅 / microRNA / p27 / MLPA / Ubiquitin ligase / 細胞周期制御因子 / ubiquitin ligase / Pirh2 / 遺伝子多型
Outline of Final Research Achievements

We analyzed the involvement of Akt in lung carcinomas. Results were, i) Microarray analysis revealed 28 miRNAs upregulated in AKT1 or AKT2-amplified carcinomas, including miR-200. Carcinomas with lymph vessel invasion had lower expression of miR-200a/b and in adenocarcinoma and in the early carcinomas, miR-200a was higher in AKT2-amplified group. MiR-200a was significantly correlated with the expression of its target, EphA. ii) Expressions of p27 and ubiquitin ligase Skp2, KPC and Pirh2 were analyzed. Cytoplasmic p27 was correlated with nodal metastasis and, inverse correlation between nuclear-p27 and Pirh2 was observed. Moreover, Pirh2 was correlated with Stage and overall survival. iii) We performed multiplex ligation-dependent probe amplification (MLPA) analysis with fluorescence in situ hybridization analysis and immunohistochemistry. By placing modified cutoff values, cases containing fewer cancer cells with gene increase could be picked up by MLPA using custom-made probes.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (33 results)

All 2017 2016 2015 2014

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Acknowledgement Compliant: 8 results,  Open Access: 8 results) Presentation (17 results) Book (1 results)

  • [Journal Article] Gene amplification of CCNE1 CCND1, and CDK6 in gastric cancers detected by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization。2017

    • Author(s)
      Ooi A et al.
    • Journal Title

      Hum Pathol

      Volume: 61 Pages: 58-67

    • DOI

      10.1016/j.humpath.2016.10.025

    • NAID

      120006226784

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Regulation of p27 by ubiquitin ligases and its pathological significance in human lung carcinomas2017

    • Author(s)
      Dobashi Y, Tsubochi H, Minegishi K, Kitagawa M, Otani S, Ooi A.
    • Journal Title

      Human Pathology

      Volume: 66 Pages: 67-68

    • DOI

      10.1016/j.humpath.2017.05.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of p27 by ubiquitin ligases and its pathological significance in human lung carcinomas.2017

    • Author(s)
      Dobashi. Y., Tsubochi, H. Minegishi, K., Kitagawa, M., Otani, S. and Ooi, A.
    • Journal Title

      Hum Pathol.

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Loss of YAP1 defines neuroendocrine differentiation of lung tumors.2016

    • Author(s)
      Ito T, Matsubara D, Tanaka I, Makiya K, Tanei ZI, Kumagai Y, Shiu SJ, Nakaoka HJ, Ishikawa S, Isagawa T, Morikawa T, Shinozaki-Ushiku A, Goto Y, Nakano T, Tsuchiya T, Tsubochi H, Komura D, Aburatani H, Dobashi Y, Nakajima J, Endo S, Fukayama M, Sekido Y, Niki T, Murakami Y.
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 10 Pages: 1527-1538

    • DOI

      10.1111/cas.13013

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNAs associated with increased AKT gene number in human lung carcinoma.2016

    • Author(s)
      Goto A, Dobashi Y, Tsubochi H, Maeda D, Ooi A
    • Journal Title

      Hum Pathol

      Volume: 印刷中 Pages: 1-10

    • DOI

      10.1016/j.humpath.2016.04.011

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A case of severe uterine bleeding postpartum following manual removal of placenta increta.2016

    • Author(s)
      Chikazawa, K., Akashi, K., Gomi, Y., Tachibana, K., Horiuchi, I., Dobashi, Y., Okochi, T., Hamamoto, K., Tanno, K. and Takagi K.
    • Journal Title

      Taiwan J Obst. Gynecol.

      Volume: 55 Issue: 6 Pages: 913-4

    • DOI

      10.1016/j.tjog.2015.09.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNAs associated with increased AKT gene number in human lung carcinoma2016

    • Author(s)
      Goto. A., Dobashi. Y., Tsubochi, H. and Ooi, A.
    • Journal Title

      Human Pathology

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Semi-comprehensive analysis of gene amplification in gastric cancers using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.2015

    • Author(s)
      Ooi A, Oyama T, Nakamura R, Tajiri R, Ikeda H, Fushida Y, Nakamura H, Dobashi Y.
    • Journal Title

      Modern Pathology

      Volume: in press Issue: 6 Pages: 861-871

    • DOI

      10.1038/modpathol.2015.33

    • NAID

      120005593968

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas2015

    • Author(s)
      Dobashi Y, Tsubochi H, Matsubara H, Inoue J, Inazawa J, Endo S, Ooi A
    • Journal Title

      Cancer Sci

      Volume: - Issue: 6 Pages: 772-781

    • DOI

      10.1111/cas.12669

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Association between AKT1 gene polymorphism rs2498794 and smoking-related traits with reference to cancer susceptibility2015

    • Author(s)
      Nishizawa, D., Kasai, S., Hasegawa, J., Sato,N., Tanioka, F., Sugimura, H., Ikeda, K. and Dobashi, Y.
    • Journal Title

      Biomedical Research. International;

      Volume: 2015.94. Pages: 316829-316829

    • DOI

      10.1155/2015/316829

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiological and pathobiological profiles of clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period.2015

    • Author(s)
      Shindo, Y., Dobashi, Y., Sakai, T., Monma, C., Miyatani, H., Yoshida, Y.
    • Journal Title

      Int J Clin Exp Pathol.

      Volume: 8 Pages: 569-77

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intratumoral heterogeneous amplification of ERBB2 and subclonal genetic diversity in gastric cancers revealed by multiple ligation-dependent probe amplification and fluorescence in situ hybridization.2014

    • Author(s)
      Tajiri. R., Ooi. A., Fujimura, T., Dobashi, Y., Oyama, T., Nakamura, R. and Ikeda, H.
    • Journal Title

      Hum Pathol.

      Volume: 45(4) Issue: 4 Pages: 725-34

    • DOI

      10.1016/j.humpath.2013.11.004

    • NAID

      120005440337

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic aberrations as the targets of oncology research: Involvement of paraffin-embedded tissues.2014

    • Author(s)
      Dobashi. Y., Goto. A., Endo, T., and Ooi, A.
    • Journal Title

      Histol. Histopathol.

      Volume: 29 Pages: 191-205

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.2014

    • Author(s)
      Tajiri, R., Inokuchi, M., Sawada-Kitamura, S., Kawashima, H., Nakamura, R., Oyama, T., Dobashi, Y., Ooi, A.
    • Journal Title

      Pathol. Int.

      Volume: 64 Pages: 231-6

    • NAID

      120005463366

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Solitary fibrous tumor of the thymus with variegated epithelial components.2014

    • Author(s)
      Tsubochi, H., Endo, T., Sogabe, M., Endo, S., Morinaga, S. and Dobashi, Y.
    • Journal Title

      Int J Clin Exp Pathol.

      Volume: 7 Pages: 7477-84

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] MLPA とFISH を用いた乳癌における遺伝子増幅の準網羅的検索2017

    • Author(s)
      大井 章史、中村 律子、尾山 武、池田 博子、土橋 洋
    • Organizer
      第106回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2017-04-28
    • Related Report
      2016 Research-status Report
  • [Presentation] 肺癌でAKT 遺伝子増幅に伴い変動するmicroRNA とそのターゲット2017

    • Author(s)
      土橋 洋、後藤 明輝、松原 大祐、椙村 春彦、大井 章史
    • Organizer
      第106回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2017-04-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 肺癌でAKT 遺伝子増幅に伴い変動するmicroRNA とそのターゲット2017

    • Author(s)
      土橋 洋、後藤 明輝、椙村 春彦、大井 章史
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 癌におけるMLPとFISH法によるCCNDE1, CCND1, CDK6 遺伝子増幅の解析2017

    • Author(s)
      大井 章史、尾山 武、中村 律子、土橋 洋
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Gene amplification of CCNDE1, CCND1 and CDK6 in gastric cancers detected by MLPA and FISH.2016

    • Author(s)
      大井 章史、尾山 武、中村 律子、土橋 洋
    • Organizer
      第75回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 胃癌におけるサイクリンE, D1, CDK6増幅のMLPAおよびFISHによる検索.2016

    • Author(s)
      大井 章史、田尻 亮輔、中村 律子、尾山 武、池田 博子、土橋 洋.
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 胃癌におけるサイクリンE, D1, CDK6増幅のMLPAおよびFISHによる検索2016

    • Author(s)
      大井 章史、田尻 亮輔、中村 律子、尾山 武、池田 博子、土橋 洋
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-14
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト肺癌における細胞周期抑制因子p27の3種ubiquitin ligaseによる制御.2016

    • Author(s)
      土橋 洋、後藤 明輝、山田 茂樹、大井 章史.
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト肺癌における細胞周期抑制因子p27の3種ubiquitin ligaseによる制御2016

    • Author(s)
      土橋 洋、後藤 明輝、山田 茂樹、大井 章史.
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 肺癌におけるYAP1欠如と神経内分泌分化について2015

    • Author(s)
      松原 大祐、伊東 剛、田中 一大、石川 俊平、後藤 悌、中野 智 之、土橋 洋、中島 淳、遠藤 俊輔、深山 正久、関戸 好孝、仁 木 利郎、村上 善則.
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋名古屋
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] AKT increase and associated change in microRNA expression in human lung carcinomas2015

    • Author(s)
      土橋 洋、後藤 明輝、井上 純、稲澤 譲治、大井 章史
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 肺癌でAKT遺伝子増幅に伴い変動するmicroRNAとその意義.2015

    • Author(s)
      土橋 洋、椙村 春彦、山田 茂樹、大井 章史.
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-05-02
    • Related Report
      2015 Research-status Report
  • [Presentation] MLPAとFISHを用いた進行胃癌における遺伝子増幅の準網羅的検索2015

    • Author(s)
      大井 章史、尾山 武、中村 律子、田尻 亮輔、池田 博子、土橋 洋
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-05-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Significance of Akt activation and AKT gene increases in bone and soft tissue tumors.2014

    • Author(s)
      土橋 洋、坪地 宏嘉、井上 純、大井 章史.
    • Organizer
      第 73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] MLPAとFISHを用いた胃癌における増幅遺伝子の準網羅的検索.2014

    • Author(s)
      大井 章史、田尻 亮輔、尾山 武、中村 律子、土橋 洋.
    • Organizer
      第 73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト肺癌におけるAKT 遺伝子、蛋白質の異常とその意義.2014

    • Author(s)
      土橋 洋、椙村 春彦、山田 茂樹、大井 章史.
    • Organizer
      第 103回日本病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Presentation] MLPAとFISHを用いた胃癌における遺伝子増幅の準網羅的検索.2014

    • Author(s)
      大井 章史、田尻 亮輔、中村 律子、尾山 武、池田 博子、土橋 洋.
    • Organizer
      第 103回日本病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Book] 細胞傷害と細胞増殖. シンプル病理学(第7版)2015

    • Author(s)
      土橋 洋 (笹野 公伸, 岡田 保, 安井 弥編)
    • Total Pages
      15
    • Publisher
      南江堂
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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