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Researches on novel techniques of organ-selective gene therapy in thoracic surgery

Researches on novel techniques of organ-selective gene therapy in thoracic surgery
胸外科器官选择性基因治疗新技术研究
批准号:
11557100
负责人:
MATSUDA Hikaru
金额:
$8.64万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000

项目摘要

项目成果

MATSUDA Hikaru的其他基金

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中文摘要
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英文摘要
Heart failure, caused by various cardiac disorders such as dilated cardiomyopathy (DCM) and myocardial infarction, is the leading cause of death in developed countries, but no effective treatment except for the *ardic transplantation has been existed. Heart failure is pathophysiologically characterized by structural *modeling of the myocardium associated with myocyte hypertrophy, cell death and excess deposition of extracellular matrix, which causes functional impairment. Therefore, such a remodeling has emerged as a new therapeutic target of heart failure to improve the morbidity and mortality of the disease. Hepatocyte growth factor, originally cloned as a potent mitogen for mature hepatocytes, has angiogenic, anti-apoptotic and anti-fibrotic activities in various disease models, albeit not proved in the heart. In this research, we elucidated the role of HGF in the heart in the following points ; 1) We newly identified HGF as an endogenous cardioprotective factor, as HGF and c-Met/HG … More F receptor was rapidly upregulated after ischemia-reperfusion injury and HGF-administration significantly suppressed the pathological progression in ischemia-reperfusion injury. 2) In end-stage of DCM hamsters, the myocardial TGF-β1 levels, that is thought to be a crucial fibrogenic factor in chronic fibrotic disorders, increased, whereas the myocardial HGF levels significantly decreased. When the hamsters received daily administration with recombinant human HGF for 3 weeks, myocardial fibrotic area were significantly decreased, whereas the myocyte cross-sectional area was significantly increased. Moreover, the level of TGF-β1 and type I and III collagen mRNA were down-regulated and the progression of cardiac dysfunction was significantly inhibited. 3) When HGF gene was transfected into canine myocardium of rapid-pacing induced DCM, promoted the recovery in LV function, LV wall thickness, cell diameter, and angiogenesis and decreased the fibrosis and cardiomyocytes apoptosis. Our findings suggest that HGF or HGF gene therapy may be a novel therapeutic strategy for heart failure. Less
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Suzuki K et al.: "Reconstituted fusion liposomes for gene transfer in vivo and in vivo."Gene Therapy and Regulation.. 1. 65-77 (2000)
Suzuki K 等人:“用于体内和体内基因转移的重构融合脂质体。”基因治疗和调节.. 1. 65-77 (2000)
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通讯作者:
Nakamura T.Sawa Y.Matsuda H. et al.: "Myocardial protection from ischemia/reperfusion iujury by endogenous and exogenous HGF"J Clin Invest. 106. 1511-1519 (2000)
Nakamura T.Sawa Y.Matsuda H. 等人:“内源性和外源性 HGF 对心肌缺血/再灌注损伤的保护”J Clin Invest。
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Kitagawa-Sakakida S.et al.: "Active Cell Migration in Retransplanted Rat Cardiac Allografts during the Course of Chronic Rejection"The Journal of Heart and Lung Transplantation. 19(6). 584-590 (2000)
Kitakawa-Sakakida S.et al.:“慢性排斥过程中重新移植的大鼠同种异体心脏移植物中的活性细胞迁移”心肺移植杂志。
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Hayashi Y.et al.: "P-Selectin Monoclonal Antibody May Attenuate the Whole Body Inflammatory Response Induced by Cardiopulmonary Bypass."ASAIO J. 46. 334-337 (2000)
Hayashi Y.等人:“P-选择素单克隆抗体可以减弱心肺旁路引起的全身炎症反应。”ASAIO J. 46. 334-337 (2000)
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39
    Introduction of new strategy for end-stage heart failure by implantable ventricular assist device aiming to long-term-support with reintegration into society : Survey for the background and possible candidates.
    • 批准号:
      21390396
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $9.32万
    • 财政年份:
      2009
    • 负责人:
      MATSUDA Hikaru
    • 依托单位:
    Myocardial regeneration therapy using nanotechnology enhances self-regeneration in damaged myocardium
    • 批准号:
      15209046
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $29.37万
    • 财政年份:
      2003
    • 负责人:
      MATSUDA Hikaru
    • 依托单位:
    STUDIES FOR ESTABLISHMENT OF PEDIATRIC HEART AND LUNG TRANSPLANTATION IN JAPAN
    • 批准号:
      12307027
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $27.54万
    • 财政年份:
      2000
    • 负责人:
      MATSUDA Hikaru
    • 依托单位:
    MULTI-CENTER STUDIES FOR CLINICAL APPLICATION OF PEDIATRIC HEART AND LUNG TRANSPLANTATION IN JAPAN
    • 批准号:
      09307028
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $21.5万
    • 财政年份:
      1997
    • 负责人:
      MATSUDA Hikaru
    • 依托单位: