Reactive Oxygen Species in the Initiation, Survival and Racial Disparity of Uterine Leiomyoma
活性氧在子宫平滑肌瘤的发生、存活和种族差异中的作用
基本信息
- 批准号:10410463
- 负责人:
- 金额:$ 15.35万
- 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:2020-08-06 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcetatesAcuteAddressAffectAgeAreaBCL2 geneBiologicalBlack raceCell DeathCell SurvivalCellsCessation of lifeChromatinChronicDNADNA Sequence AlterationDataDevelopmentDiseaseDrug Metabolic DetoxicationEnvironmentEnzymesEstrogensEuropeEventExonsFibroid TumorGNRH1 geneGenesGenomic DNAGenomic InstabilityGonadal Steroid HormonesGrowthHigh PrevalenceHomeostasisHormonesHysterectomyIncidenceInfertilityKnowledgeLeadLearningLeiomyomaMedicalMedical Care CostsMitochondriaMolecularMolecular AnalysisMorbidity - disease rateMutationMutation AnalysisMyometrialNucleotidesOGG1 geneOxidative StressOxidesPathogenesisPathway interactionsPharmaceutical PreparationsPlayPremenopausePrevention strategyProductionProgesteroneProgesterone ReceptorsProtein FamilyPublic HealthPublishingRaceReactive Oxygen SpeciesRegulationRoleSOD2 geneSeminalSignal PathwaySteroidal EstrogenStressSuperoxide DismutaseSymptomsTestingTimeTissuesToxic effectUnited StatesUterine FibroidsWomananalogblack womendeep sequencingdisabling symptomhigh risk populationhormonal signalsinhibitorinsightmitochondrial metabolismmyometriumnovelracial differenceracial disparityreceptorrepair enzymereproductiveresponsesenescenceside effectsurvival disparitytranslational applicationstreatment strategytumortumor growthtumor initiation
项目摘要
To date, we do not understand why there is such a high prevalence of uterine leiomyoma in premenopausal
women nor do we understand the reasons for the racial disparity observed in this disease. Black women tend
to
groups.
pertains
role
DNA
hypothesize
addition,
homeostatic
and
analysis
cells
will
develop tumors earlier and are more numerous, larger in size and more symptomatic than other ethnic
We have studied the molecular mechanisms involved in leiomyoma tumor growth and survival as it
to hormones and signaling pathways and found that reactive oxygen species (ROS) plays a significant
in leiomyoma pathogenesis. Moreover, for the first time, we discovered that ROS levels and effects on
are increased in the myometrial and leiomyoma tissues of Black compared to White women. We
that ROS promotes mutations in the MED12 gene, to promote leiomyoma tumor formation. In
ROS promotes growth and survival of the leiomyoma tumors as estrogen and progesterone provide a
environment to protect the tumors from the toxicity of high ROS levels. We propose mechanistic
molecular analyses to test our hypothesis including mutational analysis upon chronic treatment with ROS,
of ER and PR occupancy on chromatin in response to ROS, and we test the BCL2 inhibitors to target
where ROS promotes senescence when estrogen and progesterone are absent. In all of our studies, we
compare the tissues from Black versus white women which willgenerate valuable and novel insight into
the racial disparity observed in leiomyoma. We will learn about early changes that may lead to leiomyoma
development as well as provide biological rationale to treat leiomyoma tumors with the BCL2 inhibitors.
到目前为止,我们还不明白为什么绝经前子宫肌瘤的发病率如此之高。
我们也不了解在这种疾病中观察到种族差异的原因。黑人女性倾向于
至
组。
涉及到
角色
脱氧核糖核酸
假设
此外,
动态平衡
和
分析
单元格
将要
与其他种族相比,肿瘤发生得更早,数量更多,体积更大,症状更多
我们已经研究了与子宫肌瘤生长和生存有关的分子机制
对激素和信号转导途径的研究发现,活性氧(ROS)起着显著的作用
在肌瘤发病机制中的作用。此外,我们第一次发现,ROS水平和对
与白人妇女相比,黑人妇女子宫肌层和子宫肌瘤组织中的蛋白增加。我们
ROS促进MED12基因的突变,从而促进肌瘤的形成。在……里面
ROS促进子宫肌瘤的生长和存活,因为雌激素和孕激素提供了
保护肿瘤免受高ROS水平的毒性的环境。我们提出机械论
分子分析来验证我们的假设,包括对ROS慢性治疗的突变分析,
ER和PR在染色质上的占有率对ROS的响应,我们测试了BCL2抑制剂的靶向性
当缺乏雌激素和黄体酮时,ROS会促进衰老。在我们所有的研究中,我们
比较黑人和白人女性的组织将产生有价值的和新的洞察力
在肌瘤中观察到的种族差异。我们将学习可能导致子宫肌瘤的早期变化
并为bcl2抑制剂治疗子宫肌瘤提供生物学基础。
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 }}
Ji-Yong Julie Kim其他文献
Ji-Yong Julie Kim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('Ji-Yong Julie Kim', 18)}}的其他基金
Reactive Oxygen Species in the Initiation, Survival and Racial Disparity of Uterine Leiomyoma
活性氧在子宫平滑肌瘤的发生、存活和种族差异中的作用
- 批准号:
10231239 - 财政年份:2020
- 资助金额:
$ 15.35万 - 项目类别:
Project 01: Understanding Racial Disparity in Endometrial Cancer through Tumor Genomics
项目01:通过肿瘤基因组学了解子宫内膜癌的种族差异
- 批准号:
10265427 - 财政年份:2020
- 资助金额:
$ 15.35万 - 项目类别:
Project 01: Understanding Racial Disparity in Endometrial Cancer through Tumor Genomics
项目01:通过肿瘤基因组学了解子宫内膜癌的种族差异
- 批准号:
10488638 - 财政年份:2020
- 资助金额:
$ 15.35万 - 项目类别:
Reactive Oxygen Species in the Initiation, Survival and Racial Disparity of Uterine Leiomyoma
活性氧在子宫平滑肌瘤的发生、存活和种族差异中的作用
- 批准号:
10655328 - 财政年份:2020
- 资助金额:
$ 15.35万 - 项目类别:
Northwestern Center for Reproductive Science Predoctoral Training Program in Reproductive Science, Medicine, and Technology
西北生殖科学中心生殖科学、医学和技术博士前培训项目
- 批准号:
10401464 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Understanding Progesterone Receptor action in Obesity for Endometrial Cancer Prevention
了解孕酮受体在肥胖中的作用以预防子宫内膜癌
- 批准号:
10221650 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Northwestern Center for Reproductive Science Predoctoral Training Program in Reproductive Science, Medicine, and Technology
西北生殖科学中心生殖科学、医学和技术博士前培训项目
- 批准号:
10163063 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
PCOS and androgen-related disease modeling and drug testing in Multi-organ Integrated Microfluidic Reproductive Platform
多器官集成微流控生殖平台中的 PCOS 和雄激素相关疾病建模和药物测试
- 批准号:
10432418 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Understanding Progesterone Receptor action in Obesity for Endometrial Cancer Prevention
了解孕酮受体在肥胖中的作用以预防子宫内膜癌
- 批准号:
10680493 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 15.35万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 15.35万 - 项目类别:
Operating Grants