Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
基本信息
- 批准号:10474484
- 负责人:
- 金额:$ 38.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgeAnimalsArchivesBiological MarkersCellsCellular Metabolic ProcessChildChronicClinicalClinical TrialsCollaborationsConsumptionDeacetylaseDiagnosisDiagnosticDichloroacetateDietDiseaseEmission-Computed TomographyEndometrialEndometriumEnergy MetabolismEnvironmentEnzymesEstrogen ReceptorsEstrogensEvaluationFatty acid glycerol estersFosteringFunctional disorderFutureGoalsGoldHuntington DiseaseImageImmuneImpairmentInfertilityInfiltrationInflammationInflammation MediatorsInflammatoryLactic acidLaparoscopyLesionMacacaMagnetic Resonance ImagingMalignant NeoplasmsMeasuresMediatingMediator of activation proteinMedicalMetabolicMetabolic DiseasesMetabolic MarkerMetabolic PathwayMetabolic dysfunctionMetabolismMethodsMitochondriaModelingMolecularMonitorMonkeysOrganOvarianPainPeritonealPeritoneal FluidPolycystic Ovary SyndromePositron-Emission TomographyPre-Clinical ModelProgesteroneProgesterone ReceptorsProteinsPyruvateRegulationReportingResearch PersonnelResistanceResolutionRespirationReview LiteratureRoleSIRT1 geneSamplingScheduleSerumSeveritiesSignal TransductionSir2-like DeacetylasesStagingSteroid ReceptorsTestingTestosteroneTherapeuticTissuesTracerUterusWarburg EffectWomanWorkX-Ray Computed Tomographyaerobic glycolysiscontrast enhancedcontrast imagingdiagnosis standarddiagnostic strategyendometriosisimprovedinflammatory markerinhibitorinsightlongitudinal analysismetabolomicsmouse modelnonhuman primatenovelnovel strategiesnovel therapeuticsobesogenicpyruvate dehydrogenasereproductiveresponsesensorside effectsymptom managementsystemic inflammatory responsetargeted treatmenttherapeutic targetultrasoundwestern diet
项目摘要
Project 3: Imaging and treatment of endometriosis in nonhuman primates
SUMMARY/ABSTRACT
The overarching goal of this P01 Center is to advance our understanding of the pathophysiology of endometriosis
in order to improve the diagnosis and treatment of the disease in women. Endometriosis is a painful disorder of
women and nonhuman primates (NHPs) in which endometrium-like tissues form estrogen-dependent lesions
outside the uterus. There is currently no cure; all approved therapies target estrogen (E2) action to manage
symptoms, which is of limited use in reproductive-age women due to unwanted side effects. Macaques provide
excellent preclinical models for testing novel therapies that have not been fully vetted for clinical trials. However,
no reliable methods exist to detect early-stage disease in either women or monkeys, and improved diagnostic
approaches are needed to evaluate new therapies. Our premise is that endometriotic cell metabolism is a novel
target for improved therapies for the disease. This premise emanates, in part, from studies that have revealed
that consumption of an obesogenic "western-style" diet (WSD) combined with testosterone (T) treatment
increases the rate and severity of endometriosis in macaques. Furthermore, a key feature of endometriotic
lesions is the presentation of chronic peritoneal inflammation. Endometrial Sirtuin 1 (SIRT1) has been reported
as a biomarker of endometriosis. SIRT 1 mediates endometrial progesterone resistance associated with
endometriosis-induced infertility. Moreover, SIRT1 is a protein deacetylase enzyme that functions as a metabolic
sensor, regulating mitochondrial respiration and aerobic glycolysis. Increased understanding of the role of SIRT1
and other inflammatory and metabolic markers may help to identify more reliable methods of diagnosis and
treatment of endometriosis. Accordingly, in Specific Aim 1, we will refine positron emission tomography-
computed tomography (PET-CT) with estrogen and progesterone receptor-specific tracers. We will monitor
endometriotic lesion size and abundance in macaques by PET-CT and ultrasound and compare the results with
a laparoscopic examination, which is currently the "gold standard" for staging the disease. In Specific Aim 2,
we will evaluate cellular mediators of inflammation, progesterone resistance, and metabolic response in serum,
peritoneal fluid, endometrium, and endometrial lesions; and quantify immune cell infiltration in endometriotic
lesions from macaques. We will correlate these measures with the lesion burden detected by PET-CT and
laparoscopy. In Specific Aim 3, we will use the macaque endometriosis model to test the effect of inhibitors
against SIRT1 (Selisistat; EX-527) and the glycolytic enzyme, pyruvate dehydrogenase (dichloroacetate; DCA).
During each aim, macaque samples will be archived for future study, and relevant findings will be used to inform
Project 1 (Dr. Young, PI; involving PET/MRI imaging and inflammation of the disease in women) and Project 2
(Dr. Jeong, PI; involving the role of SIRT1 in mediating progesterone resistance). This work is highly
complementary to the other proposed projects and will support our long-term goal of advancing novel therapies
for this debilitating disease in women.
项目3:非人灵长类动物子宫内膜异位症的影像学及治疗
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 }}
OV D SLAYDEN其他文献
OV D SLAYDEN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('OV D SLAYDEN', 18)}}的其他基金
Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
- 批准号:
10700030 - 财政年份:2021
- 资助金额:
$ 38.28万 - 项目类别:
Development of magnetic hyperthermia for the systemic treatment of endometriosis
磁热疗系统治疗子宫内膜异位症的进展
- 批准号:
10490250 - 财政年份:2021
- 资助金额:
$ 38.28万 - 项目类别:
Imaging and treatment of endometriosis in nonhuman primates
非人灵长类动物子宫内膜异位症的影像学和治疗
- 批准号:
10309094 - 财政年份:2021
- 资助金额:
$ 38.28万 - 项目类别:
A nanoparticle-based approach for surgical imaging and intraoperative treatment of endometriosis
基于纳米颗粒的子宫内膜异位症手术成像和术中治疗方法
- 批准号:
10112277 - 财政年份:2020
- 资助金额:
$ 38.28万 - 项目类别:
A nanoparticle-based approach for surgical imaging and intraoperative treatment of endometriosis
基于纳米颗粒的子宫内膜异位症手术成像和术中治疗方法
- 批准号:
9893322 - 财政年份:2020
- 资助金额:
$ 38.28万 - 项目类别:
A macaque model for endometriosis induced pelvic pain and infertility
子宫内膜异位症引起的盆腔疼痛和不孕症的猕猴模型
- 批准号:
8512128 - 财政年份:2013
- 资助金额:
$ 38.28万 - 项目类别:
A macaque model for endometriosis induced pelvic pain and infertility
子宫内膜异位症引起的盆腔疼痛和不孕症的猕猴模型
- 批准号:
8666680 - 财政年份:2013
- 资助金额:
$ 38.28万 - 项目类别:
ANALYSIS OF RNA FROM ECTOPIC ENDOMETRIUM IN RHESUS MACAQUES
恒河猴异位子宫内膜 RNA 分析
- 批准号:
8357805 - 财政年份:2011
- 资助金额:
$ 38.28万 - 项目类别:
PRECLINICAL STUDIES ON HUMAN FIBROIDS IN IMMUNODEFICIENT MICE
免疫缺陷小鼠人体肌瘤的临床前研究
- 批准号:
8357768 - 财政年份:2011
- 资助金额:
$ 38.28万 - 项目类别:
SUPPRESSION OF MENSTRUAL BLEEDING IN RHESUS MACAQUES
抑制恒河猴的月经出血
- 批准号:
8357806 - 财政年份:2011
- 资助金额:
$ 38.28万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 38.28万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 38.28万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 38.28万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 38.28万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 38.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 38.28万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 38.28万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 38.28万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 38.28万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 38.28万 - 项目类别:
Miscellaneous Programs