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Long non-coding RNA Heterogeneity in ER + Breast Cancer

ER 乳腺癌中的长非编码 RNA 异质性

基本信息

批准号：
10673205
负责人：
Roza Kamila Przanowska
金额：
$ 9.96万
依托单位：
UNIVERSITY OF VIRGINIA
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：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10673205
关键词：
Accounting Adult Affect Algorithms Angiogenesis Inhibitors Animal Model Antineoplastic Agents Antisense Oligonucleotides Benign Bioinformatics Biological Assay Brain Brain Neoplasms Cancer Biology Cancer Model Cancer Prognosis Cell physiology Cells Central Nervous System Neoplasms Cessation of life Chemicals Chemotherapy and/or radiation Classification Clinical Trials Combined Modality Therapy Data Diagnosis Diagnostic Disease Disease remission Drug Targeting Epigenetic Process Estrogen receptor positive Evaluation Excision Exhibits Exons FDA approved Focused Ultrasound Future Genes Glioblastoma Glioma Gold Grant Heterogeneity Histopathology Immune response Immune system Immunotherapy Invaded Knowledge Location Malignant - descriptor Malignant Neoplasms Malignant neoplasm of brain Maps Methodology Methods MicroRNAs Mus NF-kappa B National Cancer Institute Neoplasm Metastasis Nervous System Nervous System Neoplasms Oncogenes Oncogenic Oncolytic viruses Operative Surgical Procedures Organism Pathway interactions Patients Phase Phosphotransferases Postdoctoral Fellow Prognosis Proteins Quality of life RNA RNA delivery Recurrence Regulation Regulatory Pathway Research Research Design Research Personnel Research Project Grants Risk Role Scientist Series Signs and Symptoms Specimen Structure Structure-Activity Relationship Techniques Testing Therapeutic Time Training Translating Tumor Antibodies Tumor Burden Tumor Suppression Tumor Suppressor Proteins Untranslated RNA Work Xenograft procedure bevacizumab biomarker discovery career cell motility comparative design effective therapy experimental study improved in vivo malignant breast neoplasm migration mouse model nanoparticle neuropathology novel novel strategies novel therapeutic intervention overexpression pre-doctoral screening targeted treatment therapeutic RNA therapy development tumor tumor growth tumor progression

项目摘要

Project Summary/Abstract About 30 percent of all brain tumors and central nervous system tumors are gliomas. They also comprise 80 percent of all malignant brain tumors. Glioma is a heterogeneous disease with multiple subtypes. The neuropathological evaluation and diagnostics of brain tumor specimens are performed according to WHO Classification of Tumors of the Central Nervous System: grades I, II, III and IV. Grade I biologically benign gliomas are comparatively low risk and can be removed surgically depending on their location. Grade II low- grade gliomas (LGGs) tend to exhibit benign tendencies, but they also have a uniform rate of recurrence and increase in grade over time. Grade III-IV high-grade gliomas (including glioblastoma; GBM) are malignant and carry the worst prognosis. Despite vast amounts of research, high-grade gliomas can be very difficult to treat and most often not curative. The multimodal treatments available, like tumor excision, radiation or chemotherapy, TTF (tumor treating fields), targeted drug therapy and immunotherapy, may slow cancer progression and reduce signs and symptoms in order to maximize a patient’s quality of life. Still, the median survival time of patients with high-grade gliomas is only 12–14 months. In the F99 phase of this project, I propose structure – function studies of two lncRNAs involved in glioma/GBM progression: oncogenic LINC00152 and tumor suppressive DRAIC. The working hypothesis is that lncRNAs, like proteins, have specific functional domains responsible for their activities. To investigate the relationship between lncRNA structure and function, I propose to determine (1) the secondary structure of LINC00152 and DRAIC using SHAPE-MaP technique and (2) the functionality of DRAIC lncRNA domains in the context of suppression of migration and invasion, and inhibition of the NF-kB pathway. The proposed work will open a new field of lncRNA secondary structure-function studies, which will allow faster functional description of novel cancer-related lncRNAs and define minimal functional domains that can be used in the future for therapy. In parallel, by interacting with scientists who are experts in those fields, I will familiarize myself with animal models and histopathology of gliomas to prepare for the K00 phase of work. In the K00 phase, I will focus on how to target oncogenic long and short non-coding RNAs (ncRNAs) in gliomas, and explore novel methods to deliver the minimal functional domains of the tumor suppressor ncRNAs for glioma therapy. I will also examine how manipulating noncoding RNA structure affects an organism’s immune response to the RNA delivery. Work performed in the F99 phase to understand key regulatory pathways impacted by lncRNAs in gliomas will allow me in the K00 phase to design screens for chemicals that will target these pathways, and thus help to develop novel approaches for treating gliomas.

项目总结/文摘