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一酸化窒素供与剤併用による新規肺癌治療法開発の研究

Research Project

Project/Area Number 17790524
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

安田 浩康  東北大学, 病院, 医員 (90396482)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywords一酸化窒素 / 固形癌内部における低酸素状態 / 腫瘍内微小血管密度 / 抗癌剤耐性 / Hypoxia-inducible factor-1 / VEGF / P-glycoprotein
Research Abstract

1.臨床研究
私たちは、第2相臨床試験で未治療進行非小細胞肺癌症例においてシスプラチン・ビノレルビン(VC)治療群に比べてニトログリセリン(GTN)併用VC治療群の方が無増悪生存期間が延長することを報告した。更に、手術可能肺腺癌症例において術前にGTNを常用していた症例の切除腫瘍組織ではGTNを使用しなかった症例に比べ、HIF-1α・血管内皮成長因子(VEGF)・P-glycoprotein(P-gp)の発現は有意に減少していた。また、未治療進行肺腺癌症例において抗癌剤(ドセタキセル・カルボプラチン:DCb)投与前にGTNを3日間投与し、血漿中VEGF濃度をGTN投与前後で測定したところ、GTN投与後に血漿中VEGF濃度が-16pg/mL以上滅少する症例ではGTN併用DCbが奏効する感度・特意度が84%と高いことを報告した。
2.基礎研究
マウス肺腺癌継代細胞であるLLC細胞とマウス大腸がん継代細胞であるcolon26細胞を用いて担癌モデルを製作した。LLC細胞とcolon26細胞の双方において、腫瘍成長曲線はGTN併用シスプラチン化学療法の方がシスプラチン単独化学療法よりも有意に低値を示した。生存曲線もまたGTN併用シスプラチン化学療法の方がシスプラチン単独化学療法よりも良好であった。GTN投与により腫瘍内のHIF-1α,P-gp,VEGF発現は有意に減少レ、活性型p53蛋白は増加することが判明した。更に、予想に反してGTNは腫瘍組織への抗癌剤の薬物分配を促進しなかった。腫瘍組織の腫蕩内微小血管密度(IMD)を測定したところ、両群の間でIMDの統計学的有意差は認められなかった。
GTN投与は血管新生を介さず、腫瘍内の血流を増加することによって腫瘍内酸素分圧を増加し、HIF-1pathwayの抑制と活性型p53蛋白増加を介して抗癌剤の増感作用をもたらすことが示唆された。

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (11 results)

All 2006 2005 Other

All Journal Article (10 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Randomized Phase II Trial Comparing Nitroglycerin Plus Vinorelbine and Cisplatin With Vinorelbine and Cisplatin alone in Previously Untreated Stage IIIB/IV Non-small Cell Lung Cancer.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Journal of Clinical Oncology 24

      Pages: 688-694

    • Related Report
      2006 Annual Research Report 2005 Annual Research Report
  • [Journal Article] Nitroglycerin treatment may increase response to docetaxel and carboplatin in patients with lung adenocarcinoma.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Clinical Cancer Research 12

      Pages: 6748-6757

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      European Respiratory Journal 28

      Pages: 51-58

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association of susceptibility to the development of pneumonia in older Japanese population with the haem oxygenase-1 gene promoter polymorphism.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Journal of Medical Genetics 43

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Arterial Carboxyhemoglobin Concentrations as a Predictor for Chemosensitivity in Elderly Patients with Advanced Lung Cancer.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Journal of American Geriatrics Society 54

      Pages: 373-375

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      European Respiratory Society (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of susceptibility to the development of pneumonia in older Japanese population with the haem oxygenase-l gene promoter polymorphism,2006

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Journal of Medical Genetics (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased arterial carboxyhemoglobin concentrations in patients with chronic obstructive pulmonary disease.2005

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      American Journal of Respiratory Critical Care Medicine 171

      Pages: 1246-1251

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Partial response by nitroglycerin plus amrubicin regimen in patients with refractory and recurrent advanced non-small cell lung cancer who had received at least third-line chemotherapy : Case report.

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Cancer Therapy (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tumor hypoxia imaging with [F-18] fluoronitroimidazole in non-small-cell lung cancer.

    • Author(s)
      Hiroyasu Yasuda, et al.
    • Journal Title

      Journal of American Geriatrics Society (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] POTENTIATING AGENT FOR EFFECT OF ANTICANCER AGENT2005

    • Inventor(s)
      Hiroyasu Yasuda
    • Industrial Property Rights Holder
      Hiroyasu Yasuda
    • Filing Date
      2005-06-10
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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