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Basic study on development of combination treatments for curative radiotherapy and surgery using regererative medicine

Research Project

Project/Area Number 14571293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionNational Cancer Center Research Institute

Principal Investigator

SUGIYAMA Kenji  National Cancer Center Research Institute, Investigative Treatment Division, Senior Research Associate, がん治療開発部, 主任研究官 (40132766)

Co-Investigator(Kenkyū-buntansha) MUTO Manabu  National Cancer Center Research Institute, Investigative Treatment Division, Chief, がん治療開発部, 室長 (40360698)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsWound healing / Cancer / Radiotherapy / Wound complication / Pre-operative radiation / Rat skin / Anastomosis vasorum / Regenerative medicine / 形成外科 / ケラチノサイト / 移植 / 線維芽細胞 / ラット皮膚 / 皮膚再生 / 放射線 / 術前手術
Research Abstract

Pre-operative cancer radiotherapy frequently prevents the following surgical operation, since effective dose of ionized radiation induces wound complication. The purposes in this study are to clarify causes for the impaired wound healing, and to accelerate the wound healing using animal models.
One week after X-ray (30Gy) irradiation to the back of rat, full-thickness skin (2 cm-length) was incised and sutured. Impairment of wound healing was characterized by depilation, continuous inflammation, epidermal desquamation and acanthosis, in addition to absence of granulation tissue and impaired vascularization.
When incisional wounds of irradiated and non-irradiated skins were sutured each other as a model of end-to-end implantation, granulation tissues in the non-irradiated region expanded in the irradiated region of the skin. The skin of mouse, whose bone marrow has been replaced with GFP-expressing bone marrow cells, was wounded. In the non-irradiated skin, number of GFP-positive cells in … More creased after wounding, whereas, number of GFP-positive cells decreased in the irradiated skin. These findings suggested that infiltration of bone marrow-derived fibrocytes and/or activation of dermal fibroblasts may be disordered in the irradiated skin.
The expression of transforming growth factor-β(TGF-β) increased during wound healing of irradiated skins. So, to interfere with TGF-β signaling, recombinant interferon-γ was subcutaneously injected. Granulation formation by myofibroblasts was found in the region of subepidermal bulla in the irradiated skin. Moreover, the inhibitor of TGF-β receptor kinase accelerated the wound healing by suppressing continuous inflammation and ancanthosis.
Next, rat groins were irradiated, and the femoral artery and vein in skin flap were anastomosed with that of recipient rat. The irradiated femoral artery showed pachytic tunica intima, and angeitis.
In conclusion, to suppress radiation-induced impairment of wound healing, the treatment to enhance the recruitment of bone marrow derived fibrocytes and vascularization may be effective in addition to the treatment of inhibitors for TGF-β signaling. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (23 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (11 results)

  • [Journal Article] In vivo Characterization of bone-marrow-derived fibroblasts recruited into fibrotic lesions2005

    • Author(s)
      Ishii, G, Sangai, T, Sugiyama, K, et al.
    • Journal Title

      Stem Cells 23

      Pages: 669-706

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region2005

    • Author(s)
      Muto M, et al.
    • Journal Title

      Carcinogenesis 26(5)

      Pages: 1008-1012

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endoscopic mucosal resection in the stomach using the insulated-tip needle-knife.2005

    • Author(s)
      Muto M, et al.
    • Journal Title

      Endoscopy 37(2)

      Pages: 178-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] In vivo Characterization of bone-marrow-derived fibroblasts recruited into fibrotic lesions2005

    • Author(s)
      Ishii, G, Sangai, T, Sugiyama, K et al.
    • Journal Title

      Stem Cells 23

      Pages: 669-706

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region.2005

    • Author(s)
      Muto M et al.
    • Journal Title

      Carcinogenesis 26(5)

      Pages: 1008-1012

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vivo immunophenotype of bone-marrow-derived fibroblasts2005

    • Author(s)
      Ishii, G, Sangai, T, Sugiyama, K, et al.
    • Journal Title

      Stem Cells (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region2005

    • Author(s)
      Muto M, et al.
    • Journal Title

      Carcinogenesis (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites2004

    • Author(s)
      Muto M, et al.
    • Journal Title

      Cancer 101(6)

      Pages: 1375-1381

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites.2004

    • Author(s)
      Muto M et al.
    • Journal Title

      Cancer 101(6)

      Pages: 1375-1381

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] EMR as salvage treatment for patients with locoregional failure of definitive chemoradiotherapy for esophageal cancer.2003

    • Author(s)
      Hattori, S, Muto M, et al.
    • Journal Title

      Gastrointest Endosc. 58(1)

      Pages: 65-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions.2003

    • Author(s)
      Katada, C, Muto M, et al.
    • Journal Title

      Gastrointest Endosc 57(2)

      Pages: 165-169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Esophageal stenosis after endoscopic mucosai resection of superficial esophageal lesions2003

    • Author(s)
      Katada, C, Muto M, et al.
    • Journal Title

      Gastrointest Endosc 57(2)

      Pages: 165-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yokoyama T, Muto M, et al.: "Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for esophageal squamous cell carcinoma in Japanese men."Cancer Epidemiol Biomarkers Prev. 12(11). 1227-1233 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsu A, Muto M, et al.: "Controversies in the treatment of esophageal cancer from the viewpoint of medical oncology"Gan To Kagaku Ryoho. 30(9). 425-433 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikura S, Muto M, et al.: "Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus."J Clin Oncol.. 21(14). 2697-2702 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori S, Muto M, et al.: "EMR as salvage treatment for patients with locoregional failure of definitive chemoradiotherapy for esophageal cancer.."Gastrointest Endosc.. 58(1). 65-70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawai H, Muto M, et al.: "Efficacy and safety profile of S-1 in patients with metastatic gastric cancer in clinical practices : results from a post-marketing survey."Gastric Cancer.. 6. 19-23 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katada C., Muto M, et al.: "Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions."Gastrointest Endosc.. 57(2). 165-169 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉山 賢司: "大腸癌の発生、進展に関連する病変の理解 : ACF(aberrant crypt foci)"内科. 91(5). 11-15 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Katada C, Muto M, et al.: "Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions"Gastrointestinal Endoscopy. 57(2). 165-169 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Muto M, et al.: "Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer"Carcinogenesis. 23(10). 1759-1765 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Muto M, et al.: "Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer"Gastrointestinal Endoscopy. 56(4). 517-521 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyamoto S, Muto M, et al.: "A new technique for endoscopic mucosal resection with an insulated-tip electrosurgical knife improves the completeness of resection of intramucosal gastric neoplasms"Gastrointestinal Endoscopy. 55(4). 576-581 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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