Pathological classification and progression mechanism of the lung adenocarcinoma based on molecular analyses

• Project/Area Number: 24590421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Yokohama City University
• Principal Investigator: OHASHI Kenichi 横浜市立大学, 医学(系)研究科(研究院), 教授 (40231203)
• Co-Investigator(Kenkyū-buntansha): OKUDELA Koji 横浜市立大学, 医学部, 講師 (10326027)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 病理学 / がん / 肺がん / 腺がん / 間質性肺炎 / サイトカイン / ケモカイン / 特発性間質性肺炎

Outline of Final Research Achievements

By mutated KRAS and EGFR genes transfection, several kinds of cystkine and chemokine genes were elevated in bronchial cells. As for IL-1beta, its expresseion was increased in several cell lines and tissues of lung carcinomas, and the speed of proliferation was elevated by transfection. In the lung adenocarcinoma tissues, its expression was especially elevated in the high grade histological types. Expression of IL-1beta is probably associated with progression and grading of lung adenocarcinomas.
In idiopathic interstitial pneumonias(IIPs) patients, the incidence of lung carcinoma was high, and it was related to aging, male sexuality and heavy smoking habit. Pathologically, the frequency of high columnar cell subtype was high, and the frequency of EGFR gene mutation was low. As for overall survival and disease free survival, the prognosis of lung adenocarcinoma in stage I in IIPs patients was poorer than non-IIPs patients.

Research Products

• [Journal Article] Leptomeningeal melanomatosis associated with neurocutaneous melanosis (2015)
  • Author(s): Matsumura M, Okudela K, Tateishi Y, Umeda S, Mitsui H, Suzuki T, Nakayama T, Inayama Y, Ohashi K
  • Journal Title: Pathol Int Volume: 65 Pages: 100-105
  • DOI: 10.1111/pin.12238
  • Peer Reviewed
• [Journal Article] Establishment of Successively Transplantable Rabbit VX2 Cancer Cells That Express Enhanced Green Fluorescent Protein (2015)
  • Author(s): Oshiro H, Fukumura H, Nagahama K, Sato I, Sugiura K, Iobe H, Okiyama E, Nagao T, Nagashima Y, Aoki I, Yamanaka S, Murakami A, Maegawa J, Chishima T, Ichikawa Y, Ishikawa Y, Nagai T, Nomura M, Ohashi K, Okudela K.
  • Journal Title: Med Med Mol Morphol Volume: 48 Pages: 13-23
  • DOI: 10.1007/s00795-014-0071-2
  • Peer Reviewed / Open Access
• [Journal Article] A comprehensive search for microRNAs with expression profiles modulated by oncogenic KRAS: Potential involvement of miR-31 in lung carcinogenesis (2014)
  • Author(s): Okudela K, Suzuki T, Umeda S, Tateishi Y, Mitsui H, Miyagi Y, Ohashi K
  • Journal Title: Oncol Rep Volume: 32 Pages: 1374-1384
  • DOI: 10.3892/or.2014.3339
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allelic imbalance in the miR-31 host gene locus in lung cancer--its potential role in carcinogenesis (2014)
  • Author(s): Okudela K, Tateishi Y, Umeda S, Mitsui H, Suzuki T, Saito Y, Woo T, Tajiri M, Masuda M, Miyagi Y, Ohashi K
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of pulmonary hamartoma with distinctive histopathological features: adiscussion of its differential diagnosis and histogenesis. (2014)
  • Author(s): Okudela K, Umeda S, Otara M, Honda E, Ohmori T, Tajari M, Kameda Y, Ohashi K.
  • Journal Title: Pathol Int Volume: 64 Pages: 618-623
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of HDAC9 in lung cancer--potential role in lung carcinogenesis (2014)
  • Author(s): Okudela K, Mitsui H, Suzuki T, Woo T, Tateishi Y, Umeda S, Saito Y, Tajiri M, Masuda M, Ohashi K
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 213-220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic factors for brain metastases from non-small cell lung cancer with EGFR mutation: influence of stable extracranial disease and erlotinib therapy (2014)
  • Author(s): Sekine A, Satoh H, Iwasawa T, Tamura K, Hayashihara K, Saito T, Kato T, Arai M, Okudela K, Ohashi K, Ogura T
  • Journal Title: Med Oncol Volume: 31 Pages: 228-228
  • DOI: 10.1007/s12032-014-0228-9
  • Peer Reviewed / Open Access
• [Journal Article] Proteome analysis for downstream targets of oncogenic KRAS-the potential participation of CLIC4 in carcinogenesis in the lung. (2014)
  • Author(s): Okudela K, Katayama A, Woo T, Mitsui H, Suzuki T, Tateishi Y, Umeda S, Tajiri M, Masuda M, Nagahara N, Kitamura H and Ohashi K
  • Journal Title: PLoS One. Volume: 9 Pages: 1-10
  • DOI: 10.1371/journal.pone.0087193
  • Peer Reviewed / Open Access
• [Journal Article] Hepatocyte nuclear factor-1 alpha inactivated hepatocellular adenomas in patient with congenital absence of the portal vein: a case report (2013)
  • Author(s): Tateishi Y, Furuya M, Kondo F, Okudela K, Umeda S, Ohashi K
  • Journal Title: Pathol Int Volume: vol 63 Pages: 358-363
  • DOI: 10.1111/pin.12072
  • Peer Reviewed
• [Journal Article] Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance. (2013)
  • Author(s): Okudela K, Woo T, Mitsui H, Suzuki T, Tajiri M, Sakuma Y, Miyagi Y, Tateishi Y, Umeda S, Masuda M, Ohashi K
  • Journal Title: International journal of clinical and experimental pathology Volume: 6 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Expression of HDAC9 in lung cancer - potential role in lung carcinogenesis (2013)
  • Author(s): Okudela K, Mitsui H, Suzuki T, Woo T, Tateishi Y, Umeda S, Saito Y, Tajiri M, Masuda M, Ohashi K.
  • Journal Title: International journal of clinical and experimental pathology Volume: 7 Pages: 213-220
  • Peer Reviewed
• [Journal Article] Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies (2013)
  • Author(s): Arai H, Okudela K, Oshiro H, Komitsu N, Mitsui H, Nishii T, Tsuboi M, Nozawa A, Noishiki Y, Ohashi K, Inui K, Masuda M.
  • Journal Title: International journal of clinical and experimental pathology Volume: 6 Pages: 395-410
  • Peer Reviewed
• [Journal Article] Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies (2013)
  • Author(s): Arai H, Okudela K, Oshiro H, Komitsu N, Mitsui H, Nishii T, Tsuboi M, Nozawa A, Noishiki Y, Ohashi K, Inui K, Masuda M
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 395-410
  • Peer Reviewed
• [Journal Article] Expression of the potential cancer stem cell markers, CD133, CD44, ALDH1, and β-catenin, in primary lung adenocarcinoma - their prognostic significance (2013)
  • Author(s): Kajiyama H, Shibata K, Umezu T, Mizuno M, Suzuki S, Yamamoto E, Fujiwara S, Kikkawa F
  • Journal Title: Pathology International Volume: 44(2) Pages: 181-188
  • DOI: 10.1111/pin.12019
  • Peer Reviewed
• [Journal Article] Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases. (2013)
  • Author(s): Woo T, Okudela K, Mitsui H, Tajiri M, Yamamoto T, et al.
  • Journal Title: Pathology International Volume: 62 Pages: 785-791
  • DOI: 10.1111/pin.12016
  • Peer Reviewed
• [Journal Article] Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance (2013)
  • Author(s): Okudela K, Woo T, Mitsui H, Suzuki T, Tajiri M, Sakuma Y, Miyagi Y, Tateishi Y, Umeda S, Masuda M, Ohashi K
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 1-12
  • Peer Reviewed
• [Presentation] A comprehensive search for microRNAs, the expressions of which were modulated by oncogenic KRAS The potential involvement of miR-31 in lung carcinogenesis (2014)
  • Author(s): Okudela K, Suzuki T, Umeda S, Tateishi Y, Mitsui H, Miyagi Y, Ohashi K
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Exprssion of oncogenic modulator miR-31 and miR-21 are up-regulated in early CRC. (2014)
  • Author(s): Yoko Tateishi, Koji Okudela, Hideaki Mitsui, Shigeaki Umeda,Yoko Kojima, Kazuteru Watanabe, Naomi Kawano, Yoshiaki Inayama, Kenichi Ohashi.
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Expression of IL24 in lung adenocarcinoma. (2014)
  • Author(s): Shigeaki Umeda, Kohji Okudela, Yoko Tateishi, Yoko Kojima, Kenichi Ohashi.
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-25
• [Presentation] Proteome analysis for downstream targets of KRAS - CLIC4 in lung carcinogenesis (2014)
  • Author(s): 奥寺康司、片山映、永原則之、鈴木健久、三井秀昭、梅田茂明、立石陽子、禹哲漢、小島陽子、大橋健一:
  • Organizer: 日本病理学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 間質性肺炎に合併した肺癌の検討 (2014)
  • Author(s): 小島陽子、奥寺康司、鈴木健久、三井秀昭、梅田茂明、立石陽子、禹哲漢、小島陽子、大森隆広、田尻道彦、小倉高志、益田宗孝、大橋健一
  • Organizer: 日本病理学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 早期大腸癌手術症例におけるmicroRNA発現と悪性度の関連 (2014)
  • Author(s): 立石陽子、奥寺康司、三井秀昭、梅田茂明、河野尚美、大橋健一
  • Organizer: 日本病理学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 肺腺癌におけるIL-24の臨床病理学的解析. (2014)
  • Author(s): 梅田 茂明, 齋藤 悠一, 奥寺 康司, 立石 陽子, 三井 秀昭, 小島 陽子, 鈴木 健久, 松村 舞依, 大橋 健一
  • Organizer: 日本病理学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 肺癌の発生・進展におけるKRAS-miR-31経路の意義 (2013)
  • Author(s): 奥寺 康司, 立石 陽子, 梅田 茂明, 三井 秀昭, 鈴木 健久, 禹 哲漢, 田尻 道彦, 大橋 健一
  • Organizer: 日本病理学会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
• [Presentation] 肺癌の形態プロファイル分類 (2013)
  • Author(s): 奥寺 康司, 禹 哲漢, 田尻 道彦, 益田 宗孝, 梅田 茂明, 立石 陽子, 大橋 健一
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 早期大腸癌手術症例におけるmicroRNA-31発現の検討 (2013)
  • Author(s): 立石 陽子, 奥寺 康司, 梅田 茂明, 三井 秀昭, 鈴木 健久, 河野 尚美, 大橋 健一
  • Organizer: 日本病理学会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
• [Presentation] 変異型EGFR遺伝子の導入によって誘導される下流遺伝子の分子基盤について (2013)
  • Author(s): 梅田 茂明, 奥寺 康司, 立石 陽子, 三井 英明, 鈴木 健久, 大橋 健一
  • Organizer: 日本病理学会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
• [Presentation] The potential role of microRNA-31 in submucosal invasive colorectal cancer (2013)
  • Author(s): Yoko Tateishi, Koji Okudela, Hideaki Mitsui, Shigeaki Umeda, ,Yoko Kojima, Kazuteru Watanabe, Naomi Kawano, Kenichi Ohashi
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma (2012)
  • Author(s): 奥寺康司、大橋健一
  • Organizer: 第７１回日本がん学会総会
  • Place of Presentation: 札幌市教育文化会館（北海道）
• [Remarks] 横浜市立大学医学部病態病理学教室ホームページ
  • URL: http://www-user.yokohama-cu.ac.jp/~pathola/index.html