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
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)
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Gen-Sheng Feng其他文献
Gen-Sheng Feng的其他文献
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{{ 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:
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