Two-pronged therapeutic approach for glioblastoma: high dose radiation therapy then repair of radiation-induced brain injury

胶质母细胞瘤的双管齐下治疗方法：高剂量放射治疗然后修复放射引起的脑损伤

基本信息

批准号：
9751998
负责人：
Piotr Walczak
金额：
$ 15.33万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2019-11-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751998
关键词：
Achievement Acute Astrocytes Blood Vessels Brain Brain Injuries Brain Neoplasms Calcium Cells Cellular Structures Cerebrovascular system Complex Data Dependence Development Disease Dose Endothelium Engraftment Functional Imaging Glioblastoma Glioma Hemorrhage Image Immunocompetent Individual Injury Intra-Arterial Injections Ischemia Label Literature Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of brain Maximum Tolerated Dose Mitotic Modeling Molecular Molecular Biology Mus Nervous System Physiology Neuroglia Neurological Models Neurons Patients Peripheral Primary Brain Neoplasms Radiation Radiation Dose Unit Radiation Injuries Radiation induced damage Radiation therapy Regenerative Medicine Reporter Research Resistance Rodent Rodent Model Signal Transduction Site Testing Therapeutic Therapeutic Intervention Time Tissues Transgenic Animals Transgenic Organisms Transplantation Work Xenograft procedure anatomic imaging base bioluminescence imaging dysmyelination experimental study fetal imaging platform improved intravital imaging multimodality myelination nervous system disorder neuro-oncology neurorestoration oncology preservation prevent progenitor radiation effect recruit regenerative repaired restorative treatment tool treatment response treatment strategy tumor two photon microscopy white matter white matter damage

项目摘要

Over the last few decades, we have witnessed exceptional progress in the fields of regenerative medicine and oncology in terms of defining molecular mechanisms of disease, developing research tools (molecular biology, imaging, transgenic animals) and identifying treatment strategies. While these two fields have overall divergent targets they are can be envisioned as being complementary. Further interfacing is needed: in particular, the field of neuro-oncology may greatly benefit from exploiting all the recent achievements in regenerative medicine. Glioblastoma multiforme (GBM) accounts for approximately 65% of all primary brain tumors and is characterized by low survival, with only 10% of patients surviving >5 years. Radiation therapy dose escalation has been explored but now abandoned due to radiation-induced brain injury, which is primarily manifested by damage to white matter and cerebral vasculature. We believe we can make significant advancements in developing a better cure for GBM. Our preliminary experiments indicate that tumors can be completely eradicated with radiation therapy provided that the dose is sufficiently high. We have shown complete elimination of tumors without reoccurrence with a single dose of 40 or 80 Gy. Importantly, the injury as manifested by white matter damage and the occurrence of hemorrhage as seen on magnetic resonance imaging (MRI) was detectable after 2-3 months, providing an ample time window for therapeutic intervention. We propose to perform a detailed characterization of radiation-induced brain injury following high dose radiation therapy and to test the feasibility of regenerative approaches aiming at reversing or preventing the injury to the most vulnerable components (white matter and vasculature). To this end, we will use a state-of-the art multimodal intravital imaging platform with MRI, bioluminescence imaging (BLI) and two-photon microscopy (2PM).

在过去的几十年中，我们目睹了再生医学领域的出色进步和肿瘤学在定义疾病的分子机制方面，开发研究工具（分子生物学，成像，转基因动物）并确定治疗策略。虽然这两个领域的总体不同可以将目标的目标设想为互补。需要进一步的接口：特别是神经肿瘤的领域可能会从中利用所有最新成就，从而大大受益药品。胶质母细胞瘤多形（GBM）约占所有原发性脑肿瘤的65％，IS 以低存活率为特征，只有10％的患者> 5年。放射治疗剂量升级已经探索了，但由于辐射引起的脑损伤而被放弃，这主要由损害白质和脑脉管系统。我们相信我们可以在开发更好的GBM治疗方法。我们的初步实验表明肿瘤可以完全通过放射疗法消除，规定剂量足够高。我们已经显示完整消除无需再次发生的肿瘤，单剂量为40或80 Gy。重要的是，伤害为如在磁共振上看到的白质损伤和出血的发生所表现出来 2-3个月后可以检测到成像（MRI），为治疗干预提供了充足的时间窗口。我们建议对辐射引起的脑损伤进行高剂量后的详细表征放射疗法并测试旨在逆转或防止这种再生方法的可行性最脆弱的成分（白质和脉管系统）受伤。为此，我们将使用最先进的具有MRI，生物发光成像（BLI）和两光子显微镜的ART多模式静脉成像平台（下午2点）。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Unlocking the potential of ultra-high dose fractionated radiation for effective treatment of glioblastoma.

释放超高剂量分割放射有效治疗胶质母细胞瘤的潜力。

DOI：
10.21203/rs.3.rs-3500563/v1
发表时间：
2023
期刊：
Research square
影响因子：
0
作者：
Lan,Xiao-Yan;Kalkowski,Lukasz;Chu,Cheng-Yan;Jablonska,Anna;Li,Shen;Kai,Mihoko;Gao,Yue;Janowski,Miroslaw;Walczak,Piotr
通讯作者：
Walczak,Piotr