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

Sex Differences in Blood-Brain and Blood-Tumor Barrier Dynamics in Glioblastoma

胶质母细胞瘤血脑和血肿瘤屏障动力学的性别差异

基本信息

批准号：
10886931
负责人：
Samuel Adam Tyler Sprowls
金额：
$ 3.84万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-12 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10886931
关键词：
Animal Model Animals Astrocytes Award Blood Blood - brain barrier anatomy Blood Vessels Blood capillaries Brain Breast Cancer Model Breast Cancer Patient Breast Cancer cell line Breast cancer metastasis Cancer Center Cancer Etiology Central Nervous System Neoplasms Cessation of life Clinical Data Consensus Coupled Data Dependence Diagnosis Dose ERBB2 gene Endothelial Cells Environment Event Faculty Failure Fluorescence Focused Ultrasound Focused Ultrasound Therapy Foot Process Foundations Funding Glioblastoma Goals Imaging Techniques Institution Ionizing radiation Laboratory Research Lead Lesion Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of brain Mentors Mentorship Metastatic malignant neoplasm to brain Microbubbles Modeling Molecular Monitor Mus Neoplasm Metastasis Neurocognitive Deficit Neuroimmune Operative Surgical Procedures Outcome Patients Penetration Pericytes Permeability Pharmaceutical Preparations Pharmacologic Substance Phase Positioning Attribute Postdoctoral Fellow Pre-Clinical Model Protocols documentation Publications Radiation Radiation exposure Radiation therapy Regulation Reporting Research Research Personnel Research Project Grants Science Sex Differences Techniques Testing Therapeutic Time Tracer Training Universities West Virginia Woman Work advanced breast cancer anticancer research blood-brain barrier disruption blood-brain tumor barrier chemotherapy clinical translation clinically relevant cytotoxic cytotoxicity design experimental study foot human model imaging modality improved innovation malformation malignant breast neoplasm multimodality neurovascular unit novel palliative pharmacologic post-doctoral training pre-clinical programs radiation effect radiation response response standard care treatment strategy tumor

项目摘要

Project Summary Metastatic lesions encompass approximately 80% of all CNS tumors. Of that, breast cancer brain metastasis comprises a third of all brain metastases. Treatment options are few and often only offer palliative support, but include surgery, chemotherapy, and radiation therapy. Ionizing radiation is observed to disrupt the BTB, however the mechanism and time course of molecular events following radiation exposure remains poorly understood. Gap: There is currently no consensus on the sequence of events following radiation therapy for patients with brain metastases, and whether or not chemotherapy can be effectively timed with windows of greatest disruption of the BTB. My goal during the F99 phase is to elucidate the time line, at a range of clinically relevant doses, of radiation-induced BTB openings and determine if two approved therapeutics, when given at windows of greatest disruption, lead to increased cytotoxicity when timed competently rather than at random. The training plan set forth in this application employs a wide variety of experimental techniques including animal modeling of metastatic brain cancer, multiple imaging modalities, use of radiation in small animals, design of clinically translatable experiments, and conducting science with integrity in a rigorous and competitive field. This project uses an innovative approach combining our novel brain tropic breast cancer cell lines with small animal radiation techniques. Herein, we will use our unique multimodal fluorescence and phosphorescent imaging techniques to monitor changes in BTB permeability. I will complete this research under the mentorship of Dr. Paul R. Lockman, whose lab boasts a strong publication record with excellent funding in the field of brain metastases of breast cancer. The F99 phase of this award aligns with the remaining 2 years I have of my time in the Pharmaceutical and Pharmacological Sciences graduate program at West Virginia University. Our institutional environment is more than adequately positioned to conduct the research and training described in this proposal, which more than demonstrates the quality and strength offered by the faculty at our university. In the K00 phase of this award, I will identify a postdoctoral mentor at an institution with a strong cancer center allowing me to pursue further the cellular and molecular foundation of BBB/BTB regulation in brain metastases from a different, but complementary avenue. Combined together, the two phases of this award will provide me with the means to establish myself as a successful cancer researcher and enable me to lay the foundation for my own independent cancer research laboratory predicated on the study of the molecular interworking of the BTB in CNS metastatic lesions and novel treatment strategies.

项目总结