An evaluation for identification of signaling pathway to make progress EMT of thoracic malignant tumor and evaluation of clinical specimens.

• Project/Area Number: 25462190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SHIMOKAWA Hidehiko 産業医科大学, 医学部, 非常勤医師 (00566135)
• Co-Investigator(Kenkyū-buntansha): TANAKA Fumihiro 産業医科大学, 医学部, 教授 (10283673) ; WADA Hiromi 京都大学, 医学研究科, 名誉教授 (30111975) ; SABE Hisataka 北海道大学, 医学(系)研究科(研究院), 教授 (40187282) ; URAMOTO Hidetaka 産業医科大学, 医学部, 准教授 (90389445)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胸部悪性腫瘍 / p-EGFR / GEP100 / Arf6 / 予後

Outline of Final Research Achievements

To overcome resistance to treatment in lung cancer, it is necessary to reveal biological factors contributing to its progression. The aim of the current study is to reveal the roles of the EGFR-GEP100-Arf6 axis in controlling migration and adhesion of tumor cells and to assess its clinical applications. First, we immunohistochemically examined expression of these molecules in resected lung adenocarcinoma cases (n=182), and showed that expression of these molecules was significantly associated with poor prognosis, suggesting that the EGFR-GEP100-Arf6 axis plays important roles in invasion and metastasis that are responsible to poor prognosis. Next, we examined biological factors contributing to development and progression of malignant mesothelioma, and revealed that some EMT-related factors were significant prognostic factors that can be potentially useful clinical marker in malignant mesothelioma.

Research Products

• [Journal Article] ZEB1 Mediates Acquired Resistance to the Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. (2016)
  • Author(s): Yoshida T, Song L, Bai Y, Kinose F, Li J, Ohaegbulam KC, Munoz-Antonia T, Qu X, Eschrich S, Uramoto H, Tanaka F, Nasarre P, Gemmill RM, Roche J, Drabkin HA, Haura EB.
  • Journal Title: PLoS One Volume: 11(1) Issue: 1 Pages: e0147344-e0147344
  • DOI: 10.1371/journal.pone.0147344
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TMPRSS4 Expression as a Marker of Recurrence in Patients with Lung Cancer. (2016)
  • Author(s): Chikaishi Y, Uramoto H, Koyanagi Y, Yamada S, Yano S, Tanaka F.
  • Journal Title: Anticancer Res Volume: 36(1) Pages: 121-7
  • Peer Reviewed
• [Journal Article] rognostic impact of clinical variables on surgically resected small-cell lung cancer: Results of a retrospective multicenter analysis (FIGHT002A and HOT1301A) (2015)
  • Author(s): Yokouchi H, Ishida T, Yamazaki S, Kikuchi H, Oizumi S, Uramoto H, Tanaka F, Harada M, Akie K, Sugaya F, Fujita Y, Fukuhara T, Takamura K, Kojima T, Harada T, Higuchi M, Matsuura Y, Honjo O, Minami Y, Watanabe N, Nishihara H, Suzuki H, Dosaka-Akita H, Isobe H, Nishimura M, Munakata M
  • Journal Title: Lung Cancer Volume: 90 Issue: 3 Pages: 548-53
  • DOI: 10.1016/j.lungcan.2015.10.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The 30-day mortality and hospital mortality after chest surgery described in the annual reports published by the Japanese Association for Thoracic and Cardiovascular Surgery. (2015)
  • Author(s): Uramoto H, Okumura M, Endo S, Tanaka F, Yokomise H, Masuda M.
  • Journal Title: Gen Thorac Cardiovasc Surg. Volume: 63(5) Issue: 5 Pages: 279-83
  • DOI: 10.1007/s11748-015-0524-0
  • Peer Reviewed
• [Journal Article] In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line. (2015)
  • Author(s): Nanjo S, Yano S, et al.
  • Journal Title: Cancer Sci Volume: 106 Issue: 3 Pages: 244-52
  • DOI: 10.1111/cas.12600
  • NAID: 120005830611
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Frequency of EGFR mutations in Bangladeshi patients with adenocarcinoma of the lung. (2014)
  • Author(s): Shakib R, Kondo N, Yoneda K, Takuwa T, Hashimoto M, Orui H, Okumura Y, Tanaka F, Kumamoto K,
  • Journal Title: Int J Clin Oncol Volume: Epub ahead of print Issue: 1 Pages: 45-9
  • DOI: 10.1007/s10147-012-0515-4
  • Peer Reviewed
• [Journal Article] Erlotinib resistance in lung cancer cells mediated by integrinβ1/Src/Akt-driven bypass signaling (2013)
  • Author(s): Kanda, R., Kage, M., Ono M, et al. 計12名
  • Journal Title: Cancer Res Volume: 73 Issue: 20 Pages: 6243-6253
  • DOI: 10.1158/0008-5472.can-12-4502
  • Peer Reviewed
• [Journal Article] Angiogenesis of Lung Cancer Utilizes Existing Blood Vessels Rather than Developing New Vessels Using Signals from Carcinogenesis (2013)
  • Author(s): Uramoto H
  • Journal Title: Anticancer Res Volume: 33 Pages: 1913-6
  • Peer Reviewed
• [Journal Article] Clinical Significance of Expression of Cancer/testis Antigen and Down-regulation of HLA Class-I in Patients with Stage I Non-small Cell Lung Cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Baba T, Uramoto H（11人中9番目）
  • Journal Title: Anticancer Res Volume: 33 Issue: 1 Pages: 2123-8
  • DOI: 10.1186/1756-9966-30-2
  • Peer Reviewed
• [Journal Article] Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never-smoker women with pulmonary adenocarcinoma (2013)
  • Author(s): Uramoto H
  • Journal Title: Cancer Volume: 119 Issue: 22 Pages: 2660-2660
  • DOI: 10.1002/cncr.27603
  • Peer Reviewed
• [Journal Article] Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients (2013)
  • Author(s): Baba T, Shiota H, Kuroda K, Shigematsu Y, Ichiki Y, Uramoto H（8人中6番目）
  • Journal Title: Int J Clin Oncol Volume: 18 Issue: 6 Pages: 997-1004
  • DOI: 10.1007/s10147-012-0491-8
  • Peer Reviewed
• [Journal Article] Intrapleural chemotherapy improves the survival of non-small cell lung cancer patients with positive pleural lavage cytology. (2013)
  • Author(s): Baba T, Uramoto H, Kuwata T, Takenoyama M, Chikaishi Y, Oka S, Nagata Y, Shigematsu Y, Shimokawa H, Nakagawa M, So T, Hanagiri T, Tanaka F.
  • Journal Title: Surg Today Volume: 43 Issue: 6 Pages: 648-53
  • DOI: 10.1007/s00595-012-0281-y
  • NAID: 10031176087
  • Peer Reviewed
• [Journal Article] Serum Level of Osteopontin as a Prognostic Factor in Patients Who Underwent Surgical Resection for Non-Small-Cell Lung Cancer (2013)
  • Author(s): Takenaka M, Hanagiri T, Shinohara S, Yasuda M, Chikaishi Y, Oka S, Shimokawa H, Nagata Y, Nakagawa M, Uramoto H, So T, Yamada S, Tanaka F（13人中10番目）
  • Journal Title: Clin Lung Cancer Volume: 14 Issue: 3 Pages: 288-94
  • DOI: 10.1016/j.cllc.2012.09.005
  • Peer Reviewed
• [Journal Article] Discriminative features of thin-slice CT for peripheral intrapulmonary lymph nodes. (2013)
  • Author(s): Takenaka M, Uramoto H, Shimokawa H, So T, Hanagiri T, Aoki T, Tanaka F.
  • Journal Title: Asian J Surg Volume: 36 Issue: 2 Pages: 69-73
  • DOI: 10.1016/j.asjsur.2012.11.005
  • Peer Reviewed
• [Journal Article] Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer. (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Kuroda K, Baba T, Shiota H, Ichiki Y, Nagata Y, Yasuda M, Uramoto H, So T, Takenoyama M, Tanaka F.
  • Journal Title: J Surg Res Volume: 181(2) Issue: 2 Pages: 57-63
  • DOI: 10.1016/j.jss.2012.07.029
  • Peer Reviewed
• [Journal Article] Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer. (2013)
  • Author(s): Hanagiri T1, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Iwata T, Uramoto H, So T, Tanaka F.
  • Journal Title: Lung Cancer. Volume: 81(3) Issue: 3 Pages: 475-479
  • DOI: 10.1016/j.lungcan.2013.07.001
  • Peer Reviewed
• [Journal Article] Preoperative embolization followed by palliative therapy for patients unable to undergo the complete removal of a chronic expanding hematoma: A report of a case (2013)
  • Author(s): Kuwata T, Uramoto H, Oka S, Hidehiko Shimokawa H, Shigematsu Y, Baba T, Hanagiri T, Tanaka F（8人中2番目）
  • Journal Title: Asian J Surg Volume: 36 Issue: 1 Pages: 40-2
  • DOI: 10.1016/j.asjsur.2012.06.006
  • Peer Reviewed
• [Journal Article] Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma (2012)
  • Author(s): Baba T, Tanaka F(8人中8番目)
  • Journal Title: Eur J Cardiothorac Surg. Volume: 43 Issue: 4 Pages: 759-764
  • DOI: 10.1093/ejcts/ezs426
  • Peer Reviewed
• [Presentation] 右肺静脈瘤に対し右下葉区域切除を施行した1例. (2015)
  • Author(s): 下川秀彦 菅谷将一
  • Organizer: 第32回 呼吸器外科学会
  • Place of Presentation: かがわ国際会議場（香川県高松市）
  • Year and Date: 2015-05-14
• [Presentation] Capture of EpCAM-negative circulating tumor cells (CTCs) with a “Universal CTC-Chip” (2015)
  • Author(s): Yoneda K, Chikaishi Y, Eri Kawashima R, So T, Uramoto H, Ohnaga T, Tanaka F
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] 融合遺伝子がもたらす新しいがん治療 TGFβ経路によるALK阻害剤耐性 (2013)
  • Author(s): 浦本秀隆
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] EML4-ALK、及びEGFR-TKIに対する耐性関連分子MED12に基づく新しい肺癌治療の戦略 (2013)
  • Author(s): 浦本秀隆
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: ホテルニューオータニ東京
• [Presentation] Novel malignant-mesothelioma-associated antigens (Gene-X and THBS-2) in the diagnosis of malignant pleural mesothelioma (MPM). (2013)
  • Author(s): Tanaka F, Shigematsu Y, Hanagiri T， Uramoto H, So T, Yoneda K, Takuwa T, Hashimoto M, Matsumoto S, Okumura Y, Kondo N, Hasegawa S
  • Organizer: 49th American Society of clinical oncology
  • Place of Presentation: Chicago,USA
• [Presentation] Development of detecting systems for circulating tumor cells in malignant pleural mesothelioma patients (2013)
  • Author(s): Chikaishi Y, So T, Oka S, Takenaka M, Nakagawa M, Shimokawa H, Iwata T, Nagata Y, Uramoto H, Hanagiri T, Ohnaga T, Uramoto H, Tanaka F,
  • Organizer: AACR (The American Association for Cancer Research) Meeting
  • Place of Presentation: Washington,USA