Regulation of primary metastasis in high grade serous ovarian cancer
高级别浆液性卵巢癌原发转移的调节
基本信息
- 批准号:10608098
- 负责人:
- 金额:$ 5.27万
- 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:2021-05-16 至 2025-05-15
- 项目状态:未结题
- 来源:
- 关键词:AddressAdrenergic AgentsAdrenergic beta-AntagonistsAdverse effectsAnabolismAutomobile DrivingCRISPR/Cas technologyCancer BiologyCancer PatientCellsChemicalsChemopreventionClinicalClinical ManagementCoculture TechniquesCommunicationCuesDataDevelopmentDiagnosisDiseaseDisease ProgressionDistant MetastasisEarly InterventionEpithelial CellsEpitheliumEventFDA approvedGoalsHumanImmunotherapyInvadedLesionMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of ovaryMammalian OviductsMediatorMolecularMusMutationNeoplasm MetastasisNorepinephrineOsteonectinOutcomeOvarianOvaryPI3K/AKTPathway interactionsPatient CarePatientsPeritonealPharmaceutical PreparationsPhysiciansProductionPrognosisPropranololRadiation therapyRefractoryRegulationRestRoleScientistSeriesSerousSignal TransductionSoilSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSystemTP53 geneTechniquesTestingTimeTrainingTranslatingTumor PromotersTumor Suppressor ProteinsUp-RegulationWomanXenograft procedureadvanced diseaseantagonistbeta-2 Adrenergic Receptorsbeta-adrenergic receptorclinical practicecostdrug repurposingexpectationexperimental studyhigh riskimprovedimproved outcomeinhibitorinsightmalignant phenotypemass spectrometric imagingmigrationneoplastic cellnovel strategiesovarian neoplasmoverexpressionparacrinepharmacologicprecision medicinepreventreceptorrelease factorresponsesmall hairpin RNAstandard of caretumortumor progressiontumorigenic
项目摘要
Project Summary/Abstract
High grade serous ovarian cancer (HGSOC) is both the most common and most lethal ovarian cancer
histotype. Though HGSOC has been long thought to originate in the ovary, recent evidence now suggests that
HGSOC precursor lesions in fact originate in the fallopian tube. Further, select dysplastic cells from the
fallopian tube disseminate from these precursor lesions and follow a variety of local migratory cues in order to
colonize the ovary and establish a primary HGSOC tumor. The ovary seems to facilitate the expansion and
spread of the ovary to the rest of the peritoneal space. Though this phenomenon is well documented, the
molecular mechanisms that drive the initial dissemination of dysplastic fallopian tube cells to the ovary are
poorly understood. To address this, our group has developed a new imaging mass spectrometry technique that
has allowed for unprecedented insight into the paracrine factors that create a pro-metastatic niche and allow
for the migration of fallopian tube cells toward the ovary. Using this technique, we determined that co-culture of
murine ovary explants with dysplastic tubal cells leads to consistent increases in norepinephrine secretion from
the ovary, later found to be produced by the ovary itself. This is significant, as norepinephrine is an established
tumor promoter in advanced disease, and ovarian cancer patients taking β-blockers that interfere with
norepinephrine signals typically have improved clinical outcomes. However, the role of norepinephrine in tumor
development is largely unknown. Given the wide availability, low cost, and minimal adverse effects of β-
blockers, should norepinephrine similarly enhance the development of HGSOC this may provide opportunity
for early intervention and/or chemoprevention in high-risk patients. Given the potential to directly impact clinical
practice, it is essential to further dissect both the mechanisms that direct norepinephrine biosynthesis, as well
as the downstream effects of norepinephrine during HGSOC development. Through the experiments detailed
in this proposal, we will gain valuable insight into these events in hopes of either preventing or delaying
HGSOC development in high-risk patients.
项目总结/文摘
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Fallopian tube secreted protein affects ovarian metabolites in high grade serous ovarian cancer.
- DOI:10.3389/fcell.2022.1042734
- 发表时间:2022
- 期刊:
- 影响因子:5.5
- 作者:
- 通讯作者:
Home-Built Spinning Apparatus for Drying Agarose-Based Imaging Mass Spectrometry Samples.
- DOI:10.1021/jasms.2c00044
- 发表时间:2022-07-06
- 期刊:
- 影响因子:3.2
- 作者:Lusk, Hannah J.;Levy, Sarah E.;Bergsten, Tova M.;Burdette, Joanna E.;Sanchez, Laura M.
- 通讯作者:Sanchez, Laura M.
Kaempferol, a Phytoprogestin, Induces a Subset of Progesterone-Regulated Genes in the Uterus.
- DOI:10.3390/nu15061407
- 发表时间:2023-03-15
- 期刊:
- 影响因子:5.9
- 作者:Bergsten TM;Li K;Lantvit DD;Murphy BT;Burdette JE
- 通讯作者:Burdette JE
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Tova Bergsten其他文献
Tova Bergsten的其他文献
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{{ truncateString('Tova Bergsten', 18)}}的其他基金
Regulation of primary metastasis in high grade serous ovarian cancer
高级别浆液性卵巢癌原发转移的调节
- 批准号:
10368940 - 财政年份:2021
- 资助金额:
$ 5.27万 - 项目类别:
Regulation of primary metastasis in high grade serous ovarian cancer
高级别浆液性卵巢癌原发转移的调节
- 批准号:
10229162 - 财政年份:2021
- 资助金额:
$ 5.27万 - 项目类别:
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