Molecular genetic mechanism of alpha-parficle induced human cancers : Analysis of liver carcinogenesis in Thorotrast patients.

α颗粒诱发人类癌症的分子遗传机制:Thorotrast患者肝癌发生的分析。

基本信息

  • 批准号:
    14390006
  • 负责人:
  • 金额:
    $ 7.23万
  • 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:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2004
  • 项目状态:
    已结题

项目摘要

Thorotrast, a previously used radiological contrast medium, is known to induce liver tumors consisting of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and angiosarcoma (AS) at nearly the same instance. Pathological specimens from Thorotrast patients are valuable for assessing the relevance of long-term exposure to low dose a-particles to radiation carcinogenesis. We analyzed mutations of the p53 and the K-ras genes, microsatellite instability (MSI), and loss of heterozygosity (LOH) in pathological specimens from Thorotrast-induced ICC. The major p53 mutations observed in Thorotrast ICC were the transition type, suggesting that reactive oxygen species are not likely involved in gene mutations of Thorotrast cancers. MSI frequency in Thorotrast ICC was significantly higher than that in non-Thorotrast ICC. MSI was partly attributed to the inactivation of the hMLH1 mismatch repair gene via methylation of its promoter region. Thorotrast ICC shared LOH pattern with non-Thorotrast HCC and ICC. Furthermore, we could assess the distribution and the quantity of deposited thorium using an imaging plate and a BAS image analyzer. Thorotrast was always phagocytosed by macrophages and the distribution of thorium deposits was not always consistent with that of apoptotic cells.We conclude that Thorotrast ICC is developed through complex carcinogenic steps including genomic instability and mutations of crucial genes occurred during remodeling of the liver architecture.
Thorotrast是一种以前使用的放射造影剂,已知在几乎相同的情况下诱导由肝细胞癌(HCC)、肝内胆管癌(ICC)和血管肉瘤(AS)组成的肝脏肿瘤。Thorotrast患者的病理标本对于评估长期暴露于低剂量α粒子与辐射致癌作用的相关性是有价值的。我们分析了Thorotrast诱导的ICC病理标本中p53和K-ras基因突变、微卫星不稳定性(MSI)和杂合性丢失(洛)。在Thorotrast ICC中观察到的主要p53突变为过渡型,表明活性氧不太可能参与Thorotrast癌的基因突变。Thorotrast ICC的MSI频率显著高于非Thorotrast ICC。MSI部分归因于hMLH 1错配修复基因通过其启动子区域的甲基化而失活。Thorotrast ICC与non-Thorotrast HCC和ICC具有相同的洛丢失模式。此外,我们还可以使用成像板和BAS图像分析仪评估沉积钍的分布和数量。Thorotrast总是被巨噬细胞吞噬,钍沉积物的分布并不总是与凋亡细胞的分布一致,我们得出结论,Thorotrast ICC是通过复杂的致癌步骤,包括基因组不稳定性和关键基因的突变发生在肝脏结构的重塑。

项目成果

期刊论文数量(59)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Allelic loss at 19q12 and Xq11-12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential.
19q12和XQ11-12的等位基因损失预测具有低恶性潜力的粘液性卵巢肿瘤患者的不良临床结果。
  • DOI:
    10.1038/sj.bjc.6601681
  • 发表时间:
    2004-03-22
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
  • 通讯作者:
Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma
  • DOI:
    10.1002/ijc.10726
  • 发表时间:
    2002-12-01
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Liu, D;Momoi, H;Fukumoto, M
  • 通讯作者:
    Fukumoto, M
Liu D., Fukumoto M.et al.: "Microsatellite instability in Thorotrast-induced human intrahepatic cholangiocarcinoma"Int.J.Cancer. 102(4). 366-371 (2002)
Liu D.、Fukumoto M.等人:“Thorotrast 诱导的人肝内胆管癌中的微卫星不稳定性”Int.J.Cancer。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
内藤慎二, 福本 学 他: "ラット放射線腸炎,放射線誘発癌におけるcaveolin-1の発現"長崎医学雑誌. 77(2). 73-76 (2002)
Shinji Naito,Manabu Fukumoto 等人:“大鼠放射性肠炎和辐射诱发癌症中的 Caveolin-1 表达”,Nag​​asaki Medical Journal 77(2) (2002)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Allelotypic characteristics of Thorotrast-induced intrahepatic cholangiocarcinoma : comparison to non-Thorotrast-associated liver cancers.
Thorotrast 诱导的肝内胆管癌的等位基因特征:与非 Thorotrast 相关肝癌的比较。
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Liu D;Fukumoto M et al.
  • 通讯作者:
    Fukumoto M et al.
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FUKUMOTO Manabu其他文献

FUKUMOTO Manabu的其他文献

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{{ truncateString('FUKUMOTO Manabu', 18)}}的其他基金

Development of a novel MRI contrast medium toward detection of hypoxic lesions and quantification of partial oxygen pressure
开发一种新型 MRI 造影剂,用于检测缺氧病变和量化氧分压
  • 批准号:
    23659197
  • 财政年份:
    2011
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular Epidemiological Analysis of Liver and Lung Cancers of Mayak Workers in Russia and Thorotrast Patients in Japan
俄罗斯玛雅克工人和日本胸透患者肝癌和肺癌的分子流行病学分析
  • 批准号:
    15406010
  • 财政年份:
    2003
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Evaluation of Indication for Liver Transplantation in Primary Liver Cancers : Focused on Analysis of Multicentric Liver Cancers and Relapse of Prediction.
原发性肝癌肝移植指征的评估:重点分析多中心肝癌和复发预测。
  • 批准号:
    10470048
  • 财政年份:
    1998
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
An Attempt to Clone Amplified Genes which are Overexpressed
克隆过度表达的扩增基因的尝试
  • 批准号:
    05454179
  • 财政年份:
    1993
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Analysis of Gene Amplification in Association with Carcinogenesis
基因扩增与癌变相关的分析
  • 批准号:
    03454169
  • 财政年份:
    1991
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Analysis of Oncogene Amplification and C-Myc Overexpression in Human Ovarian Cancer
人卵巢癌癌基因扩增和 C-Myc 过表达分析
  • 批准号:
    01571283
  • 财政年份:
    1989
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

Development of rapid and sensitive bioassay methods to contribute to actinide internal exposure medical response
开发快速、灵敏的生物测定方法,有助于锕系元素内照射医疗反应
  • 批准号:
    22K12384
  • 财政年份:
    2022
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Screening for individual internal exposure using teeth formed after the accident of Fukushima daiichi nuclear power plants.
使用福岛第一核电站事故后形成的牙齿筛查个人内照射。
  • 批准号:
    19K10458
  • 财政年份:
    2019
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Mechanism Study of Radioactive Microparticles in the Body by Respiration and the Risk Assessment of Internal Exposure by using an Improved Model
放射性微粒呼吸进入体内的机制研究及改进模型内照射风险评估
  • 批准号:
    19J14291
  • 财政年份:
    2019
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Conversation analysis of the internal exposure test result consultation
内暴露测试结果咨询谈话分析
  • 批准号:
    19K02112
  • 财政年份:
    2019
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Evaluation of the internal exposure effect in by the single cell - alpha particle Irradiation live imaging system.
单细胞-α粒子辐照实时成像系统内照射效果评价。
  • 批准号:
    18K11641
  • 财政年份:
    2018
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Screening for individual internal exposure using teeth
使用牙齿筛查个人内暴露
  • 批准号:
    15H05055
  • 财政年份:
    2015
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Seasonal change of radioactive contamination in edible wild plants and a method to reduce the internal exposure risk of radiocesium when collecting edible wild plants
食用野生植物放射性污染的季节变化及降低食用野生植物采集时放射性铯内照射风险的方法
  • 批准号:
    15K07496
  • 财政年份:
    2015
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    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Estimation of internal exposure from ingestion of radium isotopes in the groundwater sample and investigation of radium isotope behavior in the low-salinity groundwater environment
地下水样品中镭同位素摄入的内暴露估算以及低盐度地下水环境中镭同位素行为的研究
  • 批准号:
    26740021
  • 财政年份:
    2014
  • 资助金额:
    $ 7.23万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Establishment of dose assessment methods based on individual data for high internal exposure due to I-131 intake
根据 I-131 摄入引起的高内照射个体数据建立剂量评估方法
  • 批准号:
    26893330
  • 财政年份:
    2014
  • 资助金额:
    $ 7.23万
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Extension of standardization of radiological exposure management by applying the internal exposure management in Europe after Chernobyl
切尔诺贝利事故后欧洲通过应用内部照射管理来扩展放射照射管理的标准化
  • 批准号:
    24659326
  • 财政年份:
    2012
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