Tumor-promoting liver injuries and mechanisms
促肿瘤肝损伤及其机制
基本信息
- 批准号:10332735
- 负责人:
- 金额:$ 49.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-20 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimalsAutomobile DrivingCancer EtiologyCarcinogenesis MechanismCellsClinical TreatmentComplementConflict (Psychology)CountryDataDefectDevelopmentDiethylnitrosamineDiseaseDrug TargetingEnvironmental Risk FactorEventExcisionGene MutationGoalsHepatocarcinogenesisHepatocyteHumanIncidenceInflammatory ResponseKnock-outLeadLiverLiver diseasesMalignant - descriptorMalignant neoplasm of liverModelingMolecularMolecular AnalysisMusMutant Strains MiceMutationNFKB Signaling PathwayOncogenicOncoproteinsOutcomePathogenicityPathway interactionsPatientsPrimary Malignant Neoplasm of LiverPrimary carcinoma of the liver cellsProcessRecurrenceReportingRoleSignal TransductionSignaling MoleculeTestingTherapeuticTimeWorkbasebeta catenincarcinogenicitychemical carcinogendesignexperimental studyliver cancer modelliver cancer patientliver cell proliferationliver injurymortalitymouse modelmutantnonalcoholic steatohepatitisnovelnovel therapeutic interventionnovel therapeuticssuccesstheoriestherapeutically effectivetumortumor initiationtumor progressiontumorigenesistumorigenic
项目摘要
The goal of this project is to decipher how various liver injuries and disorders can
accelerate and exacerbate development of hepatocellular carcinoma (HCC), one leading cause
of cancer-related mortality worldwide. The immediate focus is on elucidating the tumorigenic
liver damages generated ironically by loss of pro-oncogenic molecules in hepatocytes. In recent
experiments, we found that deletion of Shp2/Ptpn11, previously known to be pro-oncogenic,
aggravated HCC development induced by diethylnitrosamine (DEN) or by Pten deficiency and
NASH. Consistently, several other groups reported that targeted removal of oncoproteins, such
as c-Met, Ikkb, and b-catenin, from hepatocytes indeed aggravated HCC induced by DEN or
other oncogenic drivers. However, the underlying mechanisms for the anti-oncogenic effect of
these oncoproteins are unclear. Our hypothesis is that loss of the pro-oncogenic molecules
generates a variety of tumor-promoting factors in the liver microenvironment, resulting in
exacerbated tumorigenesis. Of note, these mouse tumor models closely recapitulate many
aspects of the pathogenic process in liver cancer patients. Therefore, we believe that common
mechanisms or oncogenic liver disorders are shared between the mouse models and human
patients in tumor initiation and progression. On this project, we will pursue a comprehensive
analysis of the molecular and cellular events that drive hepato-carcinogenesis using several
mouse models. We propose the following three Specific Aims: 1) to search and identify
tumorigenic factors in livers deficient for c-Met, Ikkb, Shp2 or b-catenin; 2) to determine the
mutation profiles and HCC initiation in these mutants; and 3) to characterize DEN-induced and
spontaneous tumorigenesis in liver deficient for both Shp2 and Ikkb. Success of this project will
decipher common and distinctive mechanisms that drive liver tumorigenesis, and will facilitate
design of novel and effective therapeutic strategies for liver cancer.
这个项目的目标是破译各种肝脏损伤和疾病是如何
加速和加剧肝细胞癌(HCC)的发展,这是主要原因之一
全球与癌症相关的死亡率。当务之急是阐明肿瘤的致癌机制
具有讽刺意味的是,肝脏损伤是由于肝细胞中的致癌分子丢失而造成的。在最近
实验中,我们发现Shp2/Ptpn11的缺失,以前已知是促癌的,
二乙基亚硝胺(DEN)或Pten缺乏症加重肝细胞癌进展
纳什。一致地,其他几个小组报告说,有针对性地去除癌蛋白,如
肝细胞中的c-Met、IKKB和b-catenin确实加重了DEN或
其他致癌驱动因素。然而,其抗肿瘤作用的潜在机制
这些癌蛋白还不清楚。我们的假设是,致癌分子的丢失
在肝脏微环境中产生多种促肿瘤因子,导致
加剧了肿瘤的发生。值得注意的是,这些小鼠肿瘤模型紧密地概括了许多
关于肝癌患者发病过程的几个方面。因此,我们认为,共同的
机制或致癌性肝病在小鼠模型和人类之间是相同的
患者在肿瘤发生和发展中的作用。在这个项目上,我们将推行全面的
分析分子和细胞事件的驱动肝癌发生的几个
老鼠模型。我们提出了以下三个具体目标:1)搜索和识别
C-Met、IKKB、Shp2或b-catenin缺乏的肝脏中的致癌因素;2)确定
这些突变体的突变谱和肝癌的启动;以及3)表征DEN诱导的和
Shp2和IKKB基因缺陷型肝脏的自发性肿瘤发生。这个项目的成功将会
破译共同和独特的驱动肝脏肿瘤发生的机制,并将促进
设计新的、有效的肝癌治疗策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Gen-Sheng Feng其他文献
Gen-Sheng Feng的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Gen-Sheng Feng', 18)}}的其他基金
A new mechanism of hepatocyte proliferation under stress
应激下肝细胞增殖的新机制
- 批准号:
10186136 - 财政年份:2021
- 资助金额:
$ 49.3万 - 项目类别:
A new mechanism of hepatocyte proliferation under stress
应激下肝细胞增殖的新机制
- 批准号:
10577880 - 财政年份:2021
- 资助金额:
$ 49.3万 - 项目类别:
A new mechanism of hepatocyte proliferation under stress
应激下肝细胞增殖的新机制
- 批准号:
10358625 - 财政年份:2021
- 资助金额:
$ 49.3万 - 项目类别:
Project 4: Interrogating and harnessing age-related IFN signaling and innate immunity in HCC prevention and therapy
项目 4:在 HCC 预防和治疗中探究和利用与年龄相关的 IFN 信号传导和先天免疫
- 批准号:
10698110 - 财政年份:2021
- 资助金额:
$ 49.3万 - 项目类别:
Project 4: Interrogating and harnessing age-related IFN signaling and innate immunity in HCC prevention and therapy
项目 4:在 HCC 预防和治疗中探究和利用与年龄相关的 IFN 信号传导和先天免疫
- 批准号:
10270689 - 财政年份:2021
- 资助金额:
$ 49.3万 - 项目类别:
Intra- and inter-cellular signals that drive hepato-oncogenesis
驱动肝肿瘤发生的细胞内和细胞间信号
- 批准号:
10330463 - 财政年份:2020
- 资助金额:
$ 49.3万 - 项目类别:
Intra- and inter-cellular signals that drive hepato-oncogenesis
驱动肝肿瘤发生的细胞内和细胞间信号
- 批准号:
9887833 - 财政年份:2020
- 资助金额:
$ 49.3万 - 项目类别:
Intra- and inter-cellular signals that drive hepato-oncogenesis
驱动肝肿瘤发生的细胞内和细胞间信号
- 批准号:
10557925 - 财政年份:2020
- 资助金额:
$ 49.3万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 49.3万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 49.3万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 49.3万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 49.3万 - 项目类别:
Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
- 批准号:
23KK0126 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 49.3万 - 项目类别:
Training Grant














{{item.name}}会员




