Role of Kupffer Cell in Hepatic Carcinogenesis

库普弗细胞在肝癌发生中的作用

基本信息

项目摘要

DESCRIPTION (provided by applicant): Liver cancer currently ranks fifth highest of all human cancers in incidence and third highest in cancer mortality. Recent investigations have reported a dramatic increase in the incidence of the liver cancer in the US. The etiology of human liver cancer has been linked to a number of factors including hepatitis B and C infection, mycotoxin exposure, iron overload, and environmental agents. Chronic liver hyperplasia is a common feature in human liver neoplasia development and as such appears to follow the same sequential multi-step process seen in rodent liver. While the hepatocyte is the target of most liver carcinogens, recent evidence suggests that non-parenchymal cells, including the Kupffer cell (the resident liver macrophage), may be an important component of growth regulation in the liver. The Kupffer cell upon activation can produce an array of products, including reactive oxygen intermediates and cytokines, which may impact on cell growth regulation. Little is known about the role of the Kupffer cell in hepatocarcinogenesis. The long term objectives of these studies therefore are to better understand the role that the Kupffer cell plays in this process. The proposed studies will specifically examine whether activation of the Kupffer cell is important in the tumor promotion stage of hepatic tumorigenesis. The overall hypothesis of these studies is that activation of Kupffer cells result in the release of cellular growth regulatory signaling molecules that selectively produce an increase in cell proliferation in initiated cells ultimately leading to hepatic neoplasia. These studies will examine the effect of Kupffer cell activation and deactivation on both normal (noninitiated) and initiated hepatocyte growth, and will determine whether activation hepatic tumor promoting compounds activate Kupffer cells, which result in hepatocyte proliferation. The products of the tumor promoter activated Kupffer cells will be determined and examined for potential hepatocyte growth regulatory effects. In addition, the effect of Kupffer activation, either by LPS (lipopolysaccharide) or hepatic tumors promoters on preneoplastic lesion growth and normal liver growth will be investigated These studies will provide information regarding the interplay between the Kupffer cell and heptatocytes during the tumor promotion stage of hepatocarcinogenesis. These studies will further our understanding into the mechanisms of the development and progression of human liver cancer with potential application to prevention and therapy.
描述(申请人提供):目前,肝癌的发病率在所有人类癌症中排名第五,在癌症死亡率中排名第三。最近的调查报告称,美国肝癌的发病率急剧上升。人类肝癌的病因与许多因素有关,包括乙肝和丙型肝炎感染、霉菌毒素暴露、铁超载和环境因素。慢性肝脏增生是人类肝脏肿瘤发展的共同特征,因此似乎遵循与啮齿动物肝脏相同的连续多步骤过程。虽然肝细胞是大多数肝脏致癌物的靶标,但最近的证据表明,非实质细胞,包括Kupffer细胞(驻留在肝脏的巨噬细胞),可能是肝脏生长调节的重要组成部分。库普弗细胞激活后可以产生一系列的产物,包括活性氧中间体和细胞因子,这可能会影响细胞的生长调节。人们对Kupffer细胞在肝癌发生中的作用知之甚少。因此,这些研究的长期目标是更好地了解库普弗细胞在这一过程中所起的作用。这项拟议的研究将专门研究Kupffer细胞的激活是否在肝脏肿瘤发生的肿瘤促进阶段发挥重要作用。这些研究的总体假设是,Kupffer细胞的激活导致细胞生长调节信号分子的释放,这些信号分子选择性地促进启动细胞的细胞增殖,最终导致肝脏肿瘤。这些研究将检测Kupffer细胞的激活和失活对正常(非启动)和启动的肝细胞生长的影响,并将确定激活的肝肿瘤促进剂是否激活Kupffer细胞,从而导致肝细胞增殖。肿瘤促进剂激活的Kupffer细胞的产物将被检测并检查潜在的肝细胞生长调节作用。此外,还将研究Kupffer激活,无论是由脂多糖或肝肿瘤促进剂激活,对癌前病变生长和正常肝脏生长的影响。这些研究将提供关于Kupffer细胞和肝细胞在肝癌发生的促癌阶段相互作用的信息。这些研究将进一步加深我们对人类肝癌发生发展机制的理解,并有可能应用于预防和治疗。

项目成果

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JAMES E KLAUNIG其他文献

JAMES E KLAUNIG的其他文献

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{{ truncateString('JAMES E KLAUNIG', 18)}}的其他基金

The Toxicology Forum 40th Annual Summer Meeting
毒理学论坛第 40 届夏季年会
  • 批准号:
    8839077
  • 财政年份:
    2014
  • 资助金额:
    $ 23.37万
  • 项目类别:
Role of Kupffer Cell in Hepatic Carcinogenesis
库普弗细胞在肝癌发生中的作用
  • 批准号:
    6867667
  • 财政年份:
    2005
  • 资助金额:
    $ 23.37万
  • 项目类别:
Role of Kupffer Cell in Hepatic Carcinogenesis
库普弗细胞在肝癌发生中的作用
  • 批准号:
    7341146
  • 财政年份:
    2005
  • 资助金额:
    $ 23.37万
  • 项目类别:
Role of Kupffer Cell in Hepatic Carcinogenesis
库普弗细胞在肝癌发生中的作用
  • 批准号:
    7175310
  • 财政年份:
    2005
  • 资助金额:
    $ 23.37万
  • 项目类别:
Role of Kupffer Cell in Hepatic Carcinogenesis
库普弗细胞在肝癌发生中的作用
  • 批准号:
    7536435
  • 财政年份:
    2005
  • 资助金额:
    $ 23.37万
  • 项目类别:
EFFECT OF GREEN TEA AND DIETARY INTAKE ON OXIDATIVE STRESS IN SMOKERS
绿茶和饮食摄入对吸烟者氧化应激的影响
  • 批准号:
    6291090
  • 财政年份:
    1998
  • 资助金额:
    $ 23.37万
  • 项目类别:
EFFECT OF GREEN TEA AND DIETARY INTAKE ON OXIDATIVE STRESS IN SMOKERS
绿茶和饮食摄入对吸烟者氧化应激的影响
  • 批准号:
    6117793
  • 财政年份:
    1998
  • 资助金额:
    $ 23.37万
  • 项目类别:
EFFECT OF GREEN TEA AND DIETARY INTAKE ON OXIDATIVE STRESS IN SMOKERS
绿茶和饮食摄入对吸烟者氧化应激的影响
  • 批准号:
    6290937
  • 财政年份:
    1998
  • 资助金额:
    $ 23.37万
  • 项目类别:
SALICYLATE ASSAY IN CIGARETTE SMOKERS AND NONSMOKERS
吸烟者和不吸烟者的水杨酸盐测定
  • 批准号:
    6249021
  • 财政年份:
    1997
  • 资助金额:
    $ 23.37万
  • 项目类别:
EFFECT OF GREEN TEA AND DIETARY INTAKE ON OXIDATIVE STRESS IN SMOKERS
绿茶和饮食摄入对吸烟者氧化应激的影响
  • 批准号:
    6278988
  • 财政年份:
    1997
  • 资助金额:
    $ 23.37万
  • 项目类别:

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确定 G1/S 细胞周期转变如何调节成体肠道干细胞的稳态
  • 批准号:
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    $ 23.37万
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    1998
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    1998
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    $ 23.37万
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  • 批准号:
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