权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
10229162
负责人：
Tova Bergsten
金额：
$ 5.1万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
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：
https://reporter.nih.gov/project-details/10229162
关键词：
Address Adrenergic Agents Adverse effects Anabolism Automobile Driving Biological CRISPR/Cas technology Cancer Biology Cancer Patient Cells Chemicals Chemoprevention Clinical Clinical Management Coculture Techniques Communication Cues Data Development Diagnosis Disease Disease Progression Distant Metastasis Early Intervention Epithelial Epithelial Cells Event FDA approved Goals Human Image Invaded Lesion Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Mammalian Oviducts Mass Spectrum Analysis Mediator of activation protein Molecular Mus Mutation Neoplasm Metastasis Norepinephrine Osteonectin Outcome Ovarian Ovary PI3K/AKT Pathway interactions Patient Care Patients Peritoneal Pharmaceutical Preparations Pharmacology Physicians Production Prognosis Propranolol Radiation therapy Refractory Regulation Rest Role Scientist Series Serous Signal Transduction Soil Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization System TP53 gene Techniques Testing Time Training Translating Tube Tumor Promoters Tumor Suppressor Proteins Up-Regulation Woman Xenograft procedure advanced disease beta-2 Adrenergic Receptors beta-adrenergic receptor clinical practice cost drug repurposing expectation experimental study high risk improved improved outcome inhibitor/antagonist insight malignant phenotype migration neoplastic cell novel strategies ovarian neoplasm overexpression paracrine precision medicine prevent receptor release factor response small hairpin RNA standard of care tumor tumor progression tumorigenic

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