Mechanisms of Hepatoblastoma Carcinogenesis in Low Birth Weight Infants
低出生体重儿肝母细胞瘤癌变机制
基本信息
- 批准号:15591892
- 负责人:
- 金额:$ 2.05万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To verify possible roles of oxygen radicals in carcinogenesis of liver cells in premature babies, oxygen-causing oxidative DNA damage and an antioxidant enzyme activity were examined in primary cultures of rat liver cells. After oxygen exposure, 8-OHdG was significantly accumulated in a time-dependent manner particularly in the medium of liver cells derived from newborn rats. Superoxide dismutase activity was significantly lower in liver cells of newborn rats, suggesting that it was responsible for oxidative DNA damages in liver cells of newborn rats. Next, it was examined whether oxidative stresses such as hyperoxia or hypoxia caused alterations in β-catenin gene or its expression in liver cells of newborn and fetal rats. An accumulation of β-catenin protein in the nuclei was also examined. However, no genomic alterations or nuclear accumulation of β-catenin were observed in cells exposed to oxidative stresses. Third, it was examined whether oxidative stresses affected the expression of genes relating to differentiation of liver cells in fetal rats. Liver cells derived from fetal rats (day 18) were exposed to hypoxia, hyperoxia, and hypoxia and hyperoxia, and the expression of α1-AT, HNF4, AFP, albumin were examined. The expression of AFP gene was decreased as the time of culture increased, however, this was not observed in liver cells exposed to oxidative stresses. The oxidative stresses might have caused an arrest of differentiation of developing liver cells or stimulated directly the expression of AFP gene. It was suggested that oxidative stress might be responsible for hepato-carcinogenesis by affecting the differentiation of premature liver cells.
为了验证氧自由基在早产儿肝细胞致癌中的可能作用,在大鼠肝细胞的原代培养物中检测了氧引起的氧化性DNA损伤和抗氧化酶活性。氧暴露后,8-OHdG显着积累的时间依赖性的方式,特别是在培养基中的肝细胞来源于新生大鼠。超氧化物歧化酶活性在新生大鼠肝细胞中明显降低,提示其与新生大鼠肝细胞DNA氧化损伤有关。接下来,检查氧化应激(例如高氧或缺氧)是否引起新生大鼠和胎鼠肝细胞中β-连环蛋白基因或其表达的改变。还检测了β-连环蛋白在细胞核中的积累。然而,在暴露于氧化应激的细胞中没有观察到β-连环蛋白的基因组改变或核积累。第三,研究了氧化应激是否影响与胎鼠肝细胞分化相关的基因表达。取胎鼠(18 d)肝细胞,分别置于缺氧、高氧、缺氧高氧条件下,检测α1-AT、HNF 4、AFP、白蛋白的表达。AFP基因表达随培养时间的延长而降低,但在氧化应激的肝细胞中未观察到这种变化。氧化应激可能导致发育中的肝细胞分化停滞或直接刺激AFP基因的表达。提示氧化应激可能通过影响未成熟肝细胞的分化而参与肝癌的发生。
项目成果
期刊论文数量(44)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hypoxia-hyperoxia stress affects fetal rat hepatocyte differentiation
缺氧-高氧应激对胎鼠肝细胞分化的影响
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:池田 均;池田 均;Takayasu H
- 通讯作者:Takayasu H
低出生体重児の肝芽腫とその発生機序 : 酸素暴露と肝細胞のDNA酸化障害
低出生体重儿肝母细胞瘤及其发病机制:氧暴露与肝细胞DNA氧化损伤
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:池田 均;池田 均;Takayasu H;Ikeda H;Ikeda H;Takayasu H;池田 均;池田 均;Takayasu H;Takayasu H;池田 均
- 通讯作者:池田 均
シンポジウム講演 : 低出生体重児と肝芽腫 : 疫学研究から基礎研究へ
研讨会讲座:低出生体重儿与肝母细胞瘤:从流行病学研究到基础研究
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:池田 均;池田 均
- 通讯作者:池田 均
池田 均: "低出生体重児の肝芽腫とその発生機序:酸素曝露と肝細胞のDNA酸化障害"小児外科. 35・5. 556-561 (2003)
池田仁:“低出生体重儿的肝母细胞瘤及其发病机制:肝细胞中的氧暴露和DNA氧化障碍”35・5(2003年)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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{{ truncateString('IKEDA Hitoshi', 18)}}的其他基金
A novel treatment for liver injury by modulation oflipid mediator effects
通过调节脂质介质效应治疗肝损伤的新方法
- 批准号:
22590716 - 财政年份:2010
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of a role of sphingosine 1-phosphate on liver damage
阐明 1-磷酸鞘氨醇对肝损伤的作用
- 批准号:
19590750 - 财政年份:2007
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of the clinical significance of autotaxin and lysophosphatidic acid in liver diseases.
阐明自分泌运动因子和溶血磷脂酸在肝脏疾病中的临床意义。
- 批准号:
17590618 - 财政年份:2005
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of the mechanism of the inhibitory effect of sphingosine 1-phosphate on hepatocyte proliferation and the significance in liver regeneration
阐明1-磷酸鞘氨醇抑制肝细胞增殖的机制及其在肝再生中的意义
- 批准号:
14570451 - 财政年份:2002
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
-General Study of the Chinese Agriculture and Rural Economy after joining World Trade Organization-
-加入世界贸易组织后中国农业农村经济概况-
- 批准号:
14402031 - 财政年份:2002
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
PORTAL HYPERTENSION-ELUCIDATION OF THE MECHANISM IN THE LIGHT OF FUNCTIONAL ABNORMALITIES OF HEPATIC STELLATE CELLS AND DEVELOPMENT OF THERAPEUTIC STRATEGY
门静脉高压——肝星状细胞功能异常的机制阐明及治疗策略的制定
- 批准号:
12670461 - 财政年份:2000
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Pathogenetic roles of human endogenous retroviruses in autoimmune diseases
人内源性逆转录病毒在自身免疫性疾病中的致病作用
- 批准号:
12670193 - 财政年份:2000
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
ELUCIDATION OF SIGNIFICANCE OF c-met EXPRESSION IN ACTIVATED HEPATIC STELLATE GELLS AND ITS APPLICATION OF THERAPEUTIC STRATEGY
活化肝星状凝胶中c-met表达意义的阐明及其治疗策略的应用
- 批准号:
09670517 - 财政年份:1997
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mapping of the gene for Holmes' ataxia by searching of triplet repeats
通过搜索三联体重复序列绘制福尔摩斯共济失调基因图谱
- 批准号:
09470057 - 财政年份:1997
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Platelet Epidermal Growth Factor and Liver Regeneration
血小板表皮生长因子与肝脏再生
- 批准号:
62570313 - 财政年份:1987
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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