Analysis of individual difference of an epidermal growth factor receptor downstream signal system

• Project/Area Number: 22590850
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: SAKAIDA Emiko 千葉大学, 医学部附属病院, 助教 (60422218)
• Co-Investigator(Kenkyū-buntansha): TAKIGUCHI Yuichi 千葉大学, 大学院・医学研究院, 教授 (30272321)
• Co-Investigator(Renkei-kenkyūsha): TADA Yuji 千葉大学, 医学部附属病院, 助教 (50344990) ; KUROSU Katsushi 千葉大学, 医学部附属病院, 講師 (20291106) ; TANABE Nobuhiro 千葉大学, 大学院・医学研究院, 准教授 (40292700) ; TATSUMI Koichiro 千葉大学, 大学院・医学研究院, 教授 (10207061)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 非閉塞性肺疾患癌 / 肺線維症 / 呼吸器感染症 / 非閉塞性肺疾患 / 腫瘍学

Research Abstract

The purpose is to examine the role of a downstream signal system of EGFR in detail for clarifying factors other than the EGFR gene variation which determines the susceptibility of the medicine, and considering existence of the hereditary individual difference of the course. We planned clinical trial which prescribes erlotinib for the patient as second line treatment for a non-small-cell-lung-cancer case with a wild type EGFR gene, and performingbiomarker search by a cDNA microarray and RT-PCR.It checked that RNA extraction of the high purity of a tumor was possible from the minute biopsy sample of puncture under the ultrasound endoscopy (EBUS), and established the method of conducting DNA microarray analysis efficiently from a clinical sample. Furthermore, fundamental study was performed using the non-small-cell-lung-cancer-cells and mesothelioma-cells stock for the purpose of clarifying biological significance relevant to the effect of Erlotinib. Thymidylate synthase expression did not necessarily correlate with pemetrexed resistance. Metformin inhibited the proliferation of various histological types of human lung cancer cell lines, possibly by varied mechanisms including apoptosis induction and G0/G1 arrest according to the cell line.

Research Products

• [Journal Article] Antiproliferative action of metformin in human lung cancer cell lines (2012)
  • Author(s): Ashinuma H, Takiguchi Y, Sakaida E, Sekine I, et al
  • Journal Title: Oncology Reports Volume: 28(1) Pages: 8-14
  • DOI: 10.3892/or.2012.1763
  • Peer Reviewed
• [Journal Article] Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines (2012)
  • Author(s): Kitazono-Saitoh M, Takiguchi Y, Sakaida E, Sekine I, Tanabe N, et al
  • Journal Title: Oncology Reports Volume: 28(1) Pages: 33-40
  • DOI: 10.3892/or.2012.1799
  • Peer Reviewed
• [Journal Article] Evaluation of a learning system for endobronchial ultrasound-guided transbronchial needle aspiration (2012)
  • Author(s): Sakairi Y, Saegusa F, Takiguchi Y, Tatsumi K, Yoshino I, et al
  • Journal Title: Respiratory Investigation Volume: 50(2) Pages: 46-53
• [Journal Article] Feasibility of cytological diagnosis of sarcoidosis with endobronchial US-guided transbronchial aspiration (2012)
  • Author(s): Kitamura A, Takiguchi Y, Kurosu K, Tanabe N, Nakatani Y, Yoshino I, et al
  • Journal Title: Sarcoidosis, Vasculitis, And Diffuse Lung Diseases: Official Journal Of WASOG / World Association Of Sarcoidosis And Other Granulomatous Disorders Volume: 29(2) Pages: 82-89
• [Journal Article] A case report of mediastinal seminoma arising after renal transplantation (2012)
  • Author(s): Anzai M, Kenmochi T, Takiguchi Y, Matsumura C, Kanemoto K, et al
  • Journal Title: CEN Case Rep Volume: 1 Pages: 90-95
• [Journal Article] Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed (2012)
  • Author(s): Li, Q., Kawamura, K., Okamoto, S., Yamanaka, M., Yang, S., Yamauchi, S., Fukamachi, T., Kobayashi, H., Tada, Y., Takiguchi, Y., Tatsumi, K., Shimada, H., Hiroshima, K. and Tagawa, M.
  • Journal Title: Cancer Gene Ther Volume: 19 Issue: 3 Pages: 218-228
  • DOI: 10.1038/cgt.2011.86
  • Peer Reviewed
• [Journal Article] Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine tumorsfails to induce apoptosis or produce anti-tumor effects (2012)
  • Author(s): Nagakawa H, Shimozato O, Tada Y, Takiguchi Y, Tatsumi K, et al
  • Journal Title: Cellular Immunology Volume: 275(1-2) Issue: 2 Pages: 90-97
  • DOI: 10.1016/j.resinv.2012.04.002
  • Peer Reviewed
• [Journal Article] CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema (2012)
  • Author(s): Shigeta, A., Tada, Y., Wang, J.-Y., Ishizaki, S., Tuyusaki, J., Yamauchi, K., Kasahara, Y., Iesato, K., Tanabe, N., Takiguchi, Y., Sakamoto, A., Tokuhisa, T., Shibuya, K., Hiroshima, K., West, J. and Tatsumi, K.
  • Journal Title: American Journal of Physiology Volume: 303 Issue: 2 Pages: 141-151
  • DOI: 10.1152/ajplung.00337.2011
  • Peer Reviewed
• [Journal Article] Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines. (2012)
  • Author(s): Kitazono-Saitoh M, et al
  • Journal Title: Oncol Rep Volume: 28(1) Pages: 33-40
• [Journal Article] Upregulation of thioredoxin reductase 1 in human oral squamous cell carcinoma (2011)
  • Author(s): Iwasawa S, Yamano Y, Takiguchi Y, Tanzawa H, Tatsumi K, Uzawa K
  • Journal Title: Oncology Reports Volume: 25(3) Issue: 3 Pages: 637-644
  • DOI: 10.3892/or.2010.1131
• [Journal Article] Synergistic effect of non-transmissible Sendai virus vector encoding the c-myc suppressor FUSE-binding protein-interacting repressor plus cisplatin in treatment of malignant pleural mesothelioma (2011)
  • Author(s): Kitamura A, Matsushita K, Takiguchi Y, Shimada H, Tada Y, Yamanaka M, Hiroshima K, Tagawa M, Tomonaga T, Matsubara H, Inoue M, Hasegawa M, Sato Y, Levens D, Tatsumi K, Nomura F
  • Journal Title: Cancer Sci Volume: 102 Issue: 7 Pages: 1366-73
  • DOI: 10.1111/j.1349-7006.2011.01931.x
  • NAID: 10029295478
  • Peer Reviewed
• [Journal Article] Inhalation of Stachybotrys chartarum Evokes Pulmonary Arterial Remodeling in Mice,Attenuated by Rho-KinaseInhibitor (2011)
  • Author(s): Nagayoshi M, Tada Y, West J, Tanabe N, Takiguchi Y, Yasuda T, et al
  • Journal Title: Mycopathologia Volume: 172(1) Pages: 5-15
• [Journal Article] An early event of EGFR mutation in pleomorphic carcinoma of the lung (2011)
  • Author(s): Saitoh M, Niijima M, Takiguchi Y, Hiroshima K, Tatsumi K
  • Journal Title: International Journal Of Clinical Oncology / Japan Society Of Clinical Oncology Volume: 16(6) Pages: 770-773
  • NAID: 10030247775
• [Journal Article] Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography (2011)
  • Author(s): Suzuki H, Sekine Y, Mizuno S, Takiguchi Y, et al
  • Journal Title: Surgery Today Volume: 41(7) Pages: 914-921
  • NAID: 10029048516
• [Journal Article] Pushing an old issue towards a new front line (2011)
  • Author(s): Takiguchi Y
  • Journal Title: Japanese Journal Of Clinical Oncology Volume: 41(8) Pages: 935-936
• [Journal Article] Long-term administration of second-line chemotherapy with S-1 and gemcitabine for platinum-resistant non-small cell lung cancer: a phase II study (2011)
  • Author(s): Takiguchi Y, Seto T, Ichinose Y, , Minato K, Seki N, Eguchi K, Kishi K, et al
  • Journal Title: Journal Of Thoracic Oncology: Official Publication Of The International Association For The Study Of Lung Cancer Volume: 6(1) Pages: 156-160
• [Journal Article] Antitumor activity of satraplatin in cisplatin-resistant oral squamous cell carcinoma cells (2011)
  • Author(s): Yamano Y, et al
  • Journal Title: Head & Neck Volume: 33(3) Issue: 3 Pages: 309-317
  • DOI: 10.1002/hed.21445
  • Peer Reviewed
• [Journal Article] Long-term administration of second-line chemotherapy with S-1 and gemcitabine for platinum-resistant non-small cell lung cancer : a phase II study (2011)
  • Author(s): Takiguchi Y, et al
  • Journal Title: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer Volume: 6(1) Issue: 1 Pages: 156-160
  • DOI: 10.1097/jto.0b013e3181f7c76a
  • Peer Reviewed
• [Journal Article] ACTH deficiency and PGI(2) therapy in chronic thromboembolic pulmonary hypertension (2011)
  • Author(s): Ikari J, et al
  • Journal Title: International Journal Of Cardiology Volume: 146(3) Issue: 3 Pages: 449-450
  • DOI: 10.1016/j.ijcard.2010.10.115
  • Peer Reviewed
• [Journal Article] Long-term administration of second-line chemotherapy with S-1 and gemcitabine for platinum-resistant non-small cell lung cancer : a phase II study. (2011)
  • Author(s): Takiguchi Y, et al
  • Journal Title: Journal of Thoracic Oncology : Official Publication of The International Association For The Study of Lung Cancer Volume: 6(1) Pages: 156-160
  • Peer Reviewed
• [Journal Article] Upregulation of thioredoxin reductase 1 in human oral squamous cell carcinoma. (2011)
  • Author(s): Iwasawa S, et al
  • Journal Title: Oncology Reports Volume: 25(3) Pages: 637-644
  • Peer Reviewed
• [Journal Article] ACTH deficiency and PGI(2) therapy in chronic thromboembolic pulmonary hypertension. (2011)
  • Author(s): Ikari J, et al
  • Journal Title: International Journal of Cardiology Volume: 146(3) Pages: 449-450
  • Peer Reviewed
• [Journal Article] Radiation pneumonitis following twice-daily radiotherapy with concurrent carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer (2010)
  • Author(s): Kobayashi H, Uno T, Isobe K, Ueno N, Watanabe M, Harada R, Takiguchi Y, Tatsumi K, Ito H
  • Journal Title: Jpn J Clin Oncol Volume: 40(5) Issue: 5 Pages: 464-469
  • DOI: 10.1093/jjco/hyp190
• [Journal Article] Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502 (2010)
  • Author(s): Seto T, Yamanaka T, Wasada I, Seki N, Okamoto H, Ogura T, Shibuya M, Takiguchi Y, Shinkai T, Masuda N, et al
  • Journal Title: Lung Cancer Volume: 69(2) Issue: 2 Pages: 213-217
  • DOI: 10.1016/j.lungcan.2009.10.017
  • Peer Reviewed
• [Journal Article] Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer (2010)
  • Author(s): Takiguchi Y, Tada Y, Gemma A, Kudoh S, Hino M, Yoshimori K, Yoshimura A, Nagao K, Niitani H
  • Journal Title: Lung Cancer Volume: 68(3) Issue: 3 Pages: 409-14
  • DOI: 10.1016/j.lungcan.2009.08.009
  • Peer Reviewed
• [Journal Article] State of homeobox A10 expression as a putative prognostic marker for oral squamous cell carcinoma (2010)
  • Author(s): Yamatoji M, et al
  • Journal Title: Oncol Rep Volume: 23(1) Issue: 1 Pages: 61-7
  • DOI: 10.3892/or_00000606
  • Peer Reviewed
• [Journal Article] Efficacy of perioperative administration of long-acting bronchodilator on postoperative pulmonary function and quality of life in lung cancer patients with chronic obstructive pulmonary disease. Preliminary results of a randomized control study (2010)
  • Author(s): Suzuki H, et al
  • Journal Title: Surgery Today Volume: 40(10) Issue: 10 Pages: 923-930
  • DOI: 10.1007/s00595-009-4196-1
  • Peer Reviewed
• [Journal Article] Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer. (2010)
  • Author(s): Takiguchi Y, et al
  • Journal Title: Lung Cancer Volume: 68(3) Pages: 409-414
  • Peer Reviewed
• [Journal Article] Tanzawa H, Uzawa K (2010) State of homeobox A10 expression as a putative prognostic marker for oral squamous cell carcinoma. (2010)
  • Author(s): Yamatoji M, et al
  • Journal Title: Oncol Rep Volume: 23(1) Pages: 61-67
  • Peer Reviewed
• [Journal Article] Efficacy of perioperative administration of long-acting bronchodilator on postoperative pulmonary function and quality of life in lung cancer patients with chronic obstructive pulmonary disease.Preliminary results of a randomized control study. (2010)
  • Author(s): Suzuki H, et al
  • Journal Title: Surgery Today Volume: 40(10) Pages: 923-930
  • Peer Reviewed
• [Journal Article] Phase 1/11 trial of gemcitabine plus oral TS-1 in elderly patients with advanced-non-small cell lung cancer : Thoracic oncology research group study 0502. (2010)
  • Author(s): Seto T, et al
  • Journal Title: Lung Cancer (Amsterdam, Netherlands) Volume: 69(2) Pages: 213-217
  • Peer Reviewed
• [Journal Article] Radiation pneumonitis following twice-daily radiotherapy with concurrent carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer. (2010)
  • Author(s): Kobayashi H, et al
  • Journal Title: Jpn J Clin Oncol Volume: 40(5) Pages: 464-469
  • Peer Reviewed
• [Presentation] Interaction andcross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines (2012)
  • Author(s): Miyako Kitazono, Yuichi Takiguchi, Satoru Kitazono, Hironori Ashinuma, Atsushi Kitamura, Yuji Tada, Katsushi Kurosu, Emiko Sakaida, Ikuo Sekine, Nobuhiro Tanabe, Masatoshi Tagawa, Koichiro Tatsumi
  • Organizer: American Association for Cancer Research 2012 Annual Meeting
  • Place of Presentation: Chicago, IL. USA
• [Presentation] Anti-proliferative action of metformin on various types of human lung cancer cell lines (2012)
  • Author(s): Hironori Ashinuma, Yuichi Takiguchi,Satoru Kitazono, Miyako Kitazono-Saitoh, Atsushi Kitamura, Yuji Tada, Katsushi Kurosu, Emiko Sakaida, Ikuo Sekine, Nobuhiro Tanabe, Koichiro Tatsumi
  • Organizer: American Association for Cancer Research 2012 Annual Meeting
  • Place of Presentation: Chicago, IL. USA
• [Presentation] Effects of metformin on a non-small cell lung cancer cell line with an EGFR mutation (2012)
  • Author(s): Satoru Kitazono, Yuichi Takiguchi, Hironori Ashinuma, Miyako Kitazono, Atsushi Kitamura, Yuji Tada, Katsushi Kurosu, Emiko Sakaida, Ikuo Sekine, Koichiro Tatsumi
  • Organizer: American Association for Cancer Research 2012Annual Meeting
  • Place of Presentation: Chicago, IL. USA
• [Presentation] Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines (2012)
  • Author(s): Kitazono-Saitoh M et al
  • Organizer: American Association for Cancer Research 2012 Annual Meeting.
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Anti-proliferative action of metformin on various types of human lung cancer cell lines. (2012)
  • Author(s): Ashinuma H, et al
  • Organizer: American Association for Cancer Research 2012 Annual Meeting.
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Effects of metformin on a non-small cell lung cancer cell line with an EGFR mutation. (2012)
  • Author(s): Kitazono S et al
  • Organizer: American Association for Cancer Research 2012 Annual Meeting.
  • Place of Presentation: Chicago, IL, USA