Experimental investigation for the development of therapeutic approaches to inhibit metastasis to mediastinal lymph node in lung cancer

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590899
• 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: Hiroshima University
• Principal Investigator: KONDOH Tomohiro Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (40444690)
• Co-Investigator(Renkei-kenkyūsha): MIYAKE Masayuki 田附興風会医学研究所, 第5研究部, 部長 (90250076) ; KOHNO Nobuoki 広島大学, 大学院・医歯薬学総合研究科, 教授 (80215194)
• Project Period (FY): 2007 – 2008
• Keywords: 肺癌 / 縦隔リンパ節転移 / 癌転移抑制遺伝子

Research Abstract

本研究の目的は, 肺癌において最も一般的に認められる縦隔リンパ節転移を抑制する治療法はないかを検証することである. 癌転移抑制遺伝子導入を試みる遺伝子治療, 転移に関係するとされるムチン関連抗原に対する抗体療法, さらに抗腫瘍効果をうたわれるH2受容体拮抗薬(シメチジン)の投与の3つを候補として挙げた. その結果, 癌転移抑制遺伝子(MRP-1/CD9, KAI-1/CD82)の遺伝子導入により, 縦隔リンパ節への転移が著明に抑制されることが明らかとなった. シメチジンには, その抑制効果がないことも判明した. さらに, ムチン関連抗原に対する抗体療法の試みは, その抗原発現細胞のマウス生体内への移植が困難, 肺癌リンパ節転移モデルの作製が困難であることも明らかとなった.

Research Products

• [Journal Article] Perceived stress, severity of asthma and quality of life in young adults with asthma (2009)
  • Author(s): Kimura T, Yokoyama A, Kohno N, Nakamura H, Eboshida A.
  • Journal Title: Allergol Int 58 Pages: 71-79
  • Peer Reviewed
• [Journal Article] IL-12p40 is essential for the down-regulation of airway hyperresponsiveness in a mouse model of bronchial asthma with prolonged antigen exposure (2009)
  • Author(s): Onari Y, Yokoyama A, Haruta Y, Nakashima T, Iwamoto H, Hattori N, Kohno N
  • Journal Title: Clin Exp Allergy 39 Pages: 290-298
  • Peer Reviewed
• [Journal Article] Airflow limitation in smokers is associated with subclinical atherosclerosis (2009)
  • Author(s): Iwamoto H, Yokoyama A, Kitahara Y, Ishikawa N, Haruta Y, Yamane K, Hattori N, Hara H, Kohno N
  • Journal Title: Am J Respir Crit Care Med 179 Pages: 35-40
  • Peer Reviewed
• [Journal Article] Suplatast tosilate prevents bleomycin-induced pulmonary fibrosis in mice (2009)
  • Author(s): Furonaka M, Hattori N, Tanimoto T, Senoo T, Ishikawa N, Fujitaka K, Haruta Y, Yokoyama A, Kohno N
  • Journal Title: J Pharmacol Exp Ther 328 Pages: 55-61
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease (2008)
  • Author(s): Kanehara M, Yokoyama A, Tomoda Y, Shiota N, Iwamoto H, Ishikawa N, Taooka Y, Haruta Y, Hattori N, Kohno N
  • Journal Title: Pulm Pharmacol Ther 21 Pages: 874-878
  • Peer Reviewed
• [Journal Article] Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis (2008)
  • Author(s): Nakashima T, Yokoyama A, Onari Y, Shoda H, Haruta Y, Hattori N, Naka T, Kohno N
  • Journal Title: J Allergy Clin Immunol 121 Pages: 1269-1276
  • Peer Reviewed
• [Journal Article] Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors (2008)
  • Author(s): Ishikawa N, Hattori N, Yokoyama A, Tanaka S, Nishino R, Yoshioka K, Ohshimo S, Fujitaka K, Ohnishi H, Hamada H, Arihiro K, Kohno N
  • Journal Title: Int J Cancer 122 Pages: 2612-2620
  • Peer Reviewed
• [Journal Article] Circulating KL-6/MUC1 as an independent predictor for disseminated intravascular coagulation in acute respiratory distress syndrome (2008)
  • Author(s): Nakashima T, Yokoyama A, Ohnishi H, Hamada H, Ishikawa N, Haruta Y, Hattori N, Tanigawa K, Kohno N
  • Journal Title: J Intern Med 263 Pages: 432-439
  • Peer Reviewed
• [Journal Article] Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas (2007)
  • Author(s): Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y
  • Journal Title: Cancer Res 1567 Pages: 11601-11611
  • Peer Reviewed
• [Journal Article] Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia (2007)
  • Author(s): Ohtsuki Y, Fujita J, Hachisuka Y, Uomoto M, Okada Y, Yoshinouchi T, Lee GH, Furihata M, Kohno N
  • Journal Title: Med Mol Morphol 40 Pages: 198-202
  • Peer Reviewed
• [Journal Article] Activation of KIF4A as a prognostic biomarker and therapeutic target for lung cancer (2007)
  • Author(s): Taniwaki M, Takano A, Ishikawa N, Yasui W, Inai K, Nishimura H, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y
  • Journal Title: Clin Cancer Res 13(22 Pt 1) Pages: 6624-6631
  • Peer Reviewed
• [Journal Article] Differential expression of the glycosylated forms of MUC1 during lung development (2007)
  • Author(s): Sakurai J, Hattori N, Nakajima M, Moriya T, Suzuki T, Yokoyama A, Kohno N
  • Journal Title: Eur J Histochem 51 Pages: 95-102
  • Peer Reviewed
• [Journal Article] Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model (2007)
  • Author(s): Takeda T, Hattori N, Tokuhara T, Nishimura Y, Yokoyama M, Miyake M
  • Journal Title: Cancer Res 67 Pages: 1744-1749
  • Peer Reviewed