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Tumor-Targeting gene therapy and regeneration of injured lung by mssenchymal stem cells

Research Project

Project/Area Number 16390232
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTohoku University

Principal Investigator

SAIJO Yasuo  Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (10270828)

Co-Investigator(Kenkyū-buntansha) NUKIWA Toshihiro  Tohoku University, Institute of Development Aging, and Cancer, Professor, 加齢医学研究所, 教授 (40129036)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsmesenchymal stem cells / CX3CL1 / lung metastases / HGF / lung injury / gene therapy / NK4 / 肺傷害 / 固形腫瘍 / アデノウイルスベクター / 骨髄由来間葉系幹細胞
Research Abstract

1.Targeted gene therapy for multiple lung metastases by mesenchymal stem cells (MSCs) expressing CX3CL1 or NK4
1)Treatment of lung metastases by MSCs expressing CX3CL1
Lung metastases models were made by injection of B16 or C26 cells via tail vain. MSCs were infected with AdRGDCX3CL1 ex vivo (MSCs/CX3CL1). The MSCs/CX3CL1 were injected intravenously to the mice with lung metastases. This treatment inhibited development of lung metastases by inducing innate and adoptive immunity. The survival of mice also was prolonged by this treatment. This study is in press in Stem Cells.
2)Treatment of lung metastases by MSCs expressing NK4
NK4 is an antagonist against HGF which induces tumor angiogenesis, growth, and metastases. MSCs were infected with AdRGDNK4 ex vivo (MSCs/NK4). The MSCs/NK4 were injected intravenously to the mice with lung metastases. This treatment inhibited development of lung metastases by inhibiting angiogenesis The survival of mice also was prolonged by this treatment. This study is in press in Cancer Gene Therpay.
2.Treatment of injured lung by MSCs expressing HGF
1)Evaluation of lung injury by bleomycin
Bleomycin was injected intratracheally to the lung to induce lung injury. Methods of lung injury evaluation were established by measuring Ashicroft score and hydroxyproline contents.
2)Treatment of injured lung by MSCs
Bleomycin was injected intratracheally to the lung to induce lung injury. MSCs were intravenously injected to the mice pretreated with bleomycin. Treatment of MSCs improved lung injury.
HGF secretion from MSCs infected with AdRGDHGF
AdRGDHGF was made. MSCs infected with AdRGDHGF secreted large amount of HGF

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005 2004

All Journal Article (33 results)

  • [Journal Article] Targeted-delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells2007

    • Author(s)
      Xin H
    • Journal Title

      Stem Cells (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Targeted-delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells.2007

    • Author(s)
      Xin H
    • Journal Title

      Stem Cell (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phase I/II study of carboplatin combined with biweekly docetaxel for advanced non-small cell lung cancer2006

    • Author(s)
      Ishimoto O
    • Journal Title

      J Thorac Oncol 1

      Pages: 979-983

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase II study of gefitinib for pts with advanced non-small cell lung cancer with EGFR gene mutations2006

    • Author(s)
      Inoue A
    • Journal Title

      J Clin Oncol 24

      Pages: 3340-3346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dendritic cells modified to express fractalkine/CX3CL1 in the treatment of preexisting tumors2006

    • Author(s)
      Nukiwa M
    • Journal Title

      Eur J Immunol 36

      Pages: 1019-1027

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multicenter phase I study of repeated intratumoral delivery of adenoviral p53 (ADVEXIN) in patients with advanced NSCLC2006

    • Author(s)
      Fujiwara T
    • Journal Title

      J Clin Oncol 24

      Pages: 1689-1699

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced NSCLC2006

    • Author(s)
      Inoue A
    • Journal Title

      Lung Cancer 52

      Pages: 83-87

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phase 1/11 study of carboplatin combined with biweekly docetaxel for advanced : on-small cell lung cancer.2006

    • Author(s)
      shimoto O
    • Journal Title

      J Thorac Oncol 1

      Pages: 979-983

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A prospective phase 11 study of gefitinib for chemo-naive patients with advanced non-small cell lung cancer with epidermal growth factor receptor gene mutations.2006

    • Author(s)
      Inoue A
    • Journal Title

      J Clin Oncol 24

      Pages: 3340-3346

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dendritic cells modified to express fractalkine/CX3CL1 in the treatment of preexisting tumors.2006

    • Author(s)
      Nukiwa M
    • Journal Title

      Eur J lmmunol 36

      Pages: 1019-1027

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multicenter Phase I Study of Repeated Intratumoral Delivery of Adenoviral p53 (ADVEXIN) in Patients with Advanced Non-Small Cell Lung Cancer.2006

    • Author(s)
      Fujiwara T
    • Journal Title

      J Clin Oncol 24

      Pages: 1689-1699

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer.2006

    • Author(s)
      Inoue A
    • Journal Title

      Lung Cancer 52

      Pages: 83-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phase I/II study of carboplatin combined with biweekly docetaxel for advanced non-small cell lung cancer.2006

    • Author(s)
      Ishimoto O, Sugawara S, Saijo Y, et al.
    • Journal Title

      J Thorac Oncol 1

      Pages: 979-983

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A phase I study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer.2006

    • Author(s)
      Inoue A, Yamazaki K, Maemondo M, Saijo Y, et al.
    • Journal Title

      J Thorac Oncol 1

      Pages: 551-555

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A prospective phase II study of gefitinib for chemo-naive pts with advanced non-small cell lung cancer with epidermal growth factor receptor gene mutations.2006

    • Author(s)
      Inoue A, Suzuki T, Saijo Y, et al.
    • Journal Title

      J Clin Oncol 24

      Pages: 3340-3346

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dendritic cells modified to express fractalkine/CX3CL1 in the treatment of preexisting tumors.2006

    • Author(s)
      Nukiwa M, Andarini S, Saijo Y, Nukiwa T, Kikuchi T
    • Journal Title

      Eur J Immunol. 36

      Pages: 1019-1027

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multicenter phase I study of repeated intratumoral delivery of adenoviral p53 (ADVEXIN) in patients with advanced non-small cell lung cancer.2006

    • Author(s)
      Fujiwara T, Tanaka N, Kanazawa S, Saijo Y, et al.
    • Journal Title

      J Clin Oncol 24

      Pages: 1689-1699

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multicenter Phase I Study of Repeated Intratumoral Delivery of Adenoviral p53 in Patients With Advanced Non-Small-Cell Lung Cancer.2006

    • Author(s)
      Fujiwara T, Tanaka N, Kanazawa S, Ohtani S, Saijo Y, Nukiwa T et al.
    • Journal Title

      J Clin Oncol (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer.2006

    • Author(s)
      Inoue A, Usui K, Kanbe M, Gomi K, Koinumaru S, Saijo Y, Nukiwa T.
    • Journal Title

      Lung Cancer (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization2005

    • Author(s)
      Nakao S
    • Journal Title

      J Clin Invest 115

      Pages: 2979-2991

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of CX3CL1 expression by DCs in enhancement of host immunity against Legionella peumophilia2005

    • Author(s)
      Kikuchi T
    • Journal Title

      Infect Immun 73

      Pages: 5350-5357

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antitumor Immune Response by CX3CL1 Fractalkine Gene Transfer Depends on both NK and T Cells2005

    • Author(s)
      Xin H
    • Journal Title

      Eur J Immunol 35

      Pages: 1371-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vaccination of DCs loaded with IL-12 secreting cancer cells augments in vivo antitumor immunity2005

    • Author(s)
      Suzuki T
    • Journal Title

      Clin Cancer Res 11

      Pages: 58-66

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization.2005

    • Author(s)
      Nakao S
    • Journal Title

      J Clin Invest 115

      Pages: 2979-2991

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of Fractalkine/CX3CL1 expression by dendritic immunity against Legionella peumophilia cells in the enhancement of host2005

    • Author(s)
      Kikuchi T
    • Journal Title

      Infect Immun 73

      Pages: 5350-5357

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antitumor Immune Response by CX3CL1 Fractalkine Gene Transfer Depends on both NK and T Cells.2005

    • Author(s)
      Xin H
    • Journal Title

      Eur J Immunol 35

      Pages: 1371-1380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vaccination of dendritic cells loaded with Interleukin-12 secreting cancer cells augments in vivo antitumor immunity : Characteristics of syngeneic and allogeneic antigen presenting cell-cancer hybrid cells.2005

    • Author(s)
      Suzuki T
    • Journal Title

      Clin Cancer Res. 11

      Pages: 58-66

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth.2005

    • Author(s)
      Nakao S, Kuwano T, Saijo Y, Nukiwa T, Strieter RM, Kuwano M, Ono M. et al.
    • Journal Title

      J Clin Invest 115(12)

      Pages: 2979-2991

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of fractalkine/CX3CL1 expression by dendritic cells in the enhancement of host immunity against Legionella pneumophila.2005

    • Author(s)
      Kikuchi T, Andarini S, Xin H, Gomi K, Saijo Y, Honjo T, Nukiwa T.
    • Journal Title

      Infect Immun. 73(9)

      Pages: 5350-5357

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aatitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells.2005

    • Author(s)
      Xin H, Kikuchi T, Nukiwa T, Huqn, Hagiwara K, Honjo T, Saijo Y.
    • Journal Title

      Eur J Immunol 35(5)

      Pages: 1371-1380

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antitumor Immune Response by CX3CL1 Fractalkine Gene Transfer Depends on both NK and Cells2005

    • Author(s)
      Xin H, Saijo Y et al.
    • Journal Title

      European Journal of Immunology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity :2005

    • Author(s)
      Suzuki T, Saijo Y et al.
    • Journal Title

      Clinical Cancer Research 11

      Pages: 58-58

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene therapy with secretory leukoprotease inhibitor promoter controlled by replication-competent adenovirus for non-small cell lung2004

    • Author(s)
      Maemondo M, Saijo Y et al.
    • Journal Title

      Cancer Reserach 64

      Pages: 4611-4611

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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