Analysis of heterogeneity related g factors in carcinogenesis of lung cancer.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: URAMOTO Hidetaka 産業医科大学, 医学部, 講師 (90389445)
• Co-Investigator(Kenkyū-buntansha): SHIGEMATSU Yoshiki 産業医科大学, 医学部, 助教 (10546469) ; YASUMOTO Kosei 産業医科大学, 医学部, 名誉教授 (30150452) ; ONO Kenji 産業医科大学, 医学部, 助教 (40369062)
• Project Period (FY): 2009 – 2011
• Keywords: EGFR / lung cancer / heterogeneity

Research Abstract

Lung cancer has been the most common cancer in the world for several decades and the prognosis is currently unacceptable. Activating mutations in the epidermal growth factor receptor(EGFR) gene in lung adenocarcinoma are associated with a dramatic clinical response to EGFR-tyrosine kinase inhibitors(TKI). However, patients often experience a relapse. However, the whole picture and biological significance regarding acquired resistance remains unclear. in this research. We planned the experiment to establish the visualization for the cancer cell transferred for GFR gene transiently and stably by using lung cancer cell lines, measurement for tumor growth potential by co-culture, and investigation of relationship between mix ratio and drug resistance to EGFR-TKI. We also examined the clinical feature of adenosquamous cell carcinoma as a representative model for heterogeneity of the tumor. Furtherer, our results showed that various alterations in gene or protein expression can account for all resistant mechanisms and this phenomenon suggests the existence of complicated relationships among acquired resistance-related genes. We also reported that T790M may thus be a useful marker for predicting a favorable prognosis in Japanese patients treated by an EGFR-TKI.

Research Products

• [Journal Article] Clinical Significance of IGF1R Expression in Non-Small-Cell Lung Cancer (2012)
  • Author(s): Nakagawa M, Uramoto H, Oka S, Chikaishi Y, Iwanami T, Shimokawa H, So T, Hanagiri T, Tanaka F
  • Journal Title: Clin Lung Cancer Pages: 136-142
  • DOI: DOI:10.1016/j.cllc.2011.10.006
  • Peer Reviewed
• [Journal Article] Molecular diagnosis of MACC1 status in lung adenocarutinoma byimmunohistochemica analysis (2011)
  • Author(s): Gu C, Uramoto H, Onitsuka T, Shimokawa H, Iwanami T, Nakagawa M, Oyama T, Tanaka F
  • Journal Title: Anticancer Res Volume: 31 Pages: 1141-1145
  • Peer Reviewed
• [Journal Article] Preoperative CYFRA 21-1 and CEA as prognostic factors in patientswith stage I non-small cell lung cancer (2011)
  • Author(s): Hanagiri T, Sugaya M, Takenaka M, Oka S, Baba T, Shigematsu Y, Nagata Y, Shimokawa H, Uramoto H, Takenoyama M, Yasumoto K, Tanaka F
  • Journal Title: Lung Cancer Volume: 74 Pages: 112-117
  • DOI: DOI:10.1016/j.lungcan.2011.02.001
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Lymphovascular Invasion for Patients withStage I Non-Small Cell Lung Cancer (2011)
  • Author(s): Hanagiri T, Takenaka M, Oka S, Shigematsu Y, Nagata Y, Shimokawa H, Uramoto H, Yamada S, Tanaka F
  • Journal Title: Eur Surg Res Volume: 47 Pages: 211-217
  • DOI: DOI:10.1159/000333367
  • Peer Reviewed
• [Journal Article] Clinical Relevance of TAp73 andΔNp73 Protein Expression in Ovarian Cancer : A Series of 83 Cases and Review of the Literature (2011)
  • Author(s): Hofstetter G, Berger A, Chamson M, Muller-Holzner E, Reimer D, Ulmer H, Uramoto H, Marth C, G Zeimet A, Zeillinger R, Concin N
  • Journal Title: Int J Gynecol Pathol Volume: 30 Pages: 527-531
  • DOI: DOI:10.1097/PGP.0b013e31821ac519
  • Peer Reviewed
• [Journal Article] The expression of ki-67, but not proliferating cell nuclear antigen, predicts poor disease free survival in patients with adenocarcinomaof the lung (2011)
  • Author(s): Oka S. Uramoto H. Shimokawa H. Iwanami T. Tanaka F
  • Journal Title: Anticancer Res Volume: 31 Pages: 4277-4282
  • DOI: DOI:10.1097/JTO.0b013e31823ab0dd
  • Peer Reviewed
• [Journal Article] Overexpression of MACC1 mRNA in lung adenocarcinoma is associated with postoperative recurrence (2011)
  • Author(s): Shimokawa H, Uramoto H, Onitsuka T, Gu C, Hanagiri T, Oyama T, Yasumoto K
  • Journal Title: J Thorac Cardiovasc Surg Volume: 141 Pages: 895-898
  • DOI: DOI:10.1016/j.jtcvs.2010.09.044
  • Peer Reviewed
• [Journal Article] TS expression predicts postoperative recurrence in adenocarcinoma of the lung (2011)
  • Author(s): Shimokawa H, Uramoto H, Onitsuka T, Iwata T, Nakagawa M, Ono K, Hanagiri T
  • Journal Title: Lung Cancer Volume: 72 Pages: 360-364
  • DOI: DOI:10.1016/j.lungcan.2010.08.024
  • Peer Reviewed
• [Journal Article] Comment on 'Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab' (2011)
  • Author(s): Shimokawa H, Uramoto H, Tanaka F
  • Journal Title: Br J Cancer Volume: 105 Pages: 1465-1466
  • DOI: DOI:10.1038/bjc.2011.412
  • Peer Reviewed
• [Journal Article] Expression of selected gene for acquired drug resistance to EGFR-TKIin lung adenocarcinoma (2011)
  • Author(s): Uramoto H, Shimokawa H, Hanagiri T, Kuwano M, Ono M
  • Journal Title: Lung Cancer Volume: 73 Pages: 361-365
  • DOI: DOI:10.1016/j.lungcan.2011.01.008
  • Peer Reviewed
• [Journal Article] Natural air leak test without submergence for spontaneouspneumothorax (2011)
  • Author(s): Uramoto H, Tanaka F
  • Journal Title: J Cardiothorac Surg Volume: 6 Pages: 165-165
  • DOI: DOI:10.1186/1749-8090-6-165
  • Peer Reviewed
• [Journal Article] Acquired resistance to gefitinib : the contribution of mechanisms other than the T790M, MET, and HGF status (2010)
  • Author(s): Onitsuka T, Uramoto H, Nose N, Takenoyama M, Hanagiri T, Sugio K, Yasumoto K
  • Journal Title: Lung Cancer Volume: 68 Pages: 198-203
  • DOI: DOI:10.1016/j.lungcan.2009.05.022
  • Peer Reviewed
• [Journal Article] Comprehensive Molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor status (2010)
  • Author(s): Onitsuka T, Uramoto H, Ono K, Takenoyama M, Hanagiri T, Oyama T, Izumi H, Kohno K, Yasumoto K
  • Journal Title: J Thorac Oncol Volume: 5 Pages: 591-596
  • DOI: DOI:10.1097/JTO.0b013e3181d0a4db
  • Peer Reviewed
• [Journal Article] Correlation between HLA alleles and EGFR mutation in Japanese patients with adenocarcinoma of the lung (2010)
  • Author(s): Uramoto H, So T, Nagata Y, Kuroda K, Shigematsu Y, Baba T, So T, Takenoyama M, Hanagiri T, Yasumoto K
  • Journal Title: J Thorac Oncol Pages: 1136-1142
  • DOI: DOI:10.1097/JTO.0b013e3181e0b993
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of resected adenosquamous cell carcinoma of the lung : risk of coexistent double cancer (2010)
  • Author(s): Uramoto H, Yamada S, Hanagiri T
  • Journal Title: J Cardiothorac Surg Volume: 29 Pages: 92-97
  • Peer Reviewed
• [Journal Article] Loss of PTEN expression by blocking nuclear translocation of EGR1 in Gefitinib-resistant lung cancer cells harboring epidermal growth factor receptor-activating mutations (2010)
  • Author(s): Yamamoto C, Basaki Y, Kawahara A, Nakashima K, Kage M, Izumi H, Kohno K, Uramoto H, Yasumoto K, Kuwano M, Ono M
  • Journal Title: Cancer Research Volume: 70 Pages: 8715-25
  • DOI: DOI:10.1158/0008-5472.CAN-10-0043
  • Peer Reviewed
• [Journal Article] Association between lymphangiogenesis-/micrometastasis-and adhesion-related molecules in resected stage I NSCLC (2010)
  • Author(s): Yamashita T, Uramoto H, Onitsuka T, Ono K, Baba T, So T, So T, Takenoyama M, Hanagiri T, Oyama T, Yasumoto K
  • Journal Title: Lung Cancer Volume: 70 Pages: 320-328
  • DOI: DOI:10.1016/j.lungcan.2010.02.013
  • Peer Reviewed
• [Journal Article] Simple prophylactic fixation for lung torsion (2010)
  • Author(s): Uramoto H, Takenoyama M, Hanagiri T
  • Journal Title: Ann Thorac Surg Volume: 90 Pages: 2028-2030
  • DOI: DOI:10.1016/j.athoracsur.2010.07.040
  • Peer Reviewed
• [Journal Article] TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed (2010)
  • Author(s): Uramoto H, Onitsuka T, Shimokawa H, Hanagiri T
  • Journal Title: Anticancer Res Volume: 30 Pages: 4309-15
  • Peer Reviewed
• [Journal Article] Association between estrogen receptor-beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung (2009)
  • Author(s): Nose N, Sugio K, Oyama T, Nozoe T, Uramoto H, Iwata T, Onitsuka T, Yasumoto K
  • Journal Title: J Clin Oncol Volume: 27 Pages: 411-417
  • DOI: DOI:10.1200/JCO.2008.18.3251
  • Peer Reviewed
• [Presentation] 非小細胞肺癌完全切除に例に対するCBDCA+DTX術後補助化学療法の中間報告(臨床第II相試験) (2011)
  • Author(s): 浦本秀隆, 中西良一, 菅谷将一, 内山明彦, 井上政昭, 岩田輝男, 海老規之, 花桐武志, 田中文啓
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 20111103-04
• [Presentation] Association between lymphangiogenesis/micrometastasis and adhesion-related molecules in resected stageINSCLC (2011)
  • Author(s): Uramoto H, Takenaka M, Yamashita T, Chikaishi Y, Oka S, Nakagawa M, Shimokawa H, Tanaka F
  • Organizer: 2011 ISMRC
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 20110921-23
• [Presentation] Video-assisted thoracoscopic pericardiectomy for malignantpericardial effusion (2011)
  • Author(s): 浦本秀隆, 〓田泰治, 馬場哲郎, 岡壮一, 重松義紀, 下川秀彦, 永田好香, 花桐武志, 田中文啓
  • Organizer: 第34回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: アクトシティ浜松コングレスセンター
  • Year and Date: 20110616-17
• [Presentation] Simple prophylactic fixation for lung torsion (2011)
  • Author(s): 浦本秀隆, 〓田泰治, 岡壮一, 重松義紀, 馬場哲郎, 下川秀彦, 永田好香, 竹之山光広, 花桐武志, 田中文啓
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 別府国際コンベンションセンター
  • Year and Date: 20110512-13
• [Presentation] ヒト非小細胞肺癌のゲフィチニブ耐性獲得におけるPTEN欠失とその制御メカニズム (2010)
  • Author(s): 山本千鶴子, 馬崎雄二, 村上雄一, 河原明彦, 鹿毛政義, 浦本秀隆, 安元公正, 和泉弘人, 河野公俊, 桑野信彦, 小野眞弓
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪
  • Year and Date: 20100922-24
• [Presentation] Epithelial-mesenchymal transition status and EGFR mutation on EGFR-TKI-resistant lung adenocarcinoma (2010)
  • Author(s): Uramoto H, Onitsuka T, Shimokawa H, Iwata T, Nakagawa M, Nagata Y, Shigematsu Y, Baba T, Ono K, Takenoyama M, Hanagiri T, Oyama T, Yasumoto K
  • Organizer: 9th International Conference of The Asian Clinical Oncology Society
  • Place of Presentation: 岐阜グランドホテル
  • Year and Date: 20100825-27
• [Presentation] 肺腺癌手術、及びEGFR-TKI投与症例における感受性、耐性に関する分子の包括的解析と臨床的意義 (2010)
  • Author(s): 浦本秀隆, 鬼塚貴光, 重松義紀, 馬場哲郎, 宗哲哉, 小野憲司, 宗知子, 竹之山光広, 花桐武志, 安元公正
  • Organizer: 第27回日本呼吸器外科学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 20100513-14
• [Presentation] Gefitinib耐性におけるT790M, MET, HGF status以外の分子の関与 (2010)
  • Author(s): 浦本秀隆、鬼塚貴光、下川秀彦、宗哲哉、小野憲司、宗知子、竹之山光広、花桐武志、安元公正
  • Organizer: 第8回日本臨床腫瘍学会学術集会
  • Place of Presentation: 東京ビックサイト
  • Year and Date: 20100318-19
• [Presentation] EGFR-TK1の獲得耐性 (2009)
  • Author(s): 浦本秀隆、鬼塚貴光、馬場哲郎、宗哲哉、宗知子、竹之山光広、花桐武志、小山倫浩、安元公正
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20091001-03