ANTIOXIDANT INHIBITION OF GLIOMAS: MRI/MRS EVALUATION

神经胶质瘤的抗氧化剂抑制：MRI/MRS 评估

• 批准号: 7610262
• 负责人: Rheal A Towner
• 金额: $ 5.03万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610262
• 关键词: Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Basic Science; Biological Markers; Brain Neoplasms; Choline; Clinical; Computer Retrieval of Information on Scientific Projects Database; Creatine; Detection; Diagnosis; Effectiveness; Evaluation; Functional Magnetic Resonance Imaging; Funding; Future; Glioma; Grant; Human; Institution; LacZ Genes; Lipids; Magnetic Resonance; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Methods; Modeling; Monitor; N-acetylaspartate; Neurologic; Neurons; Neurosciences; Normal tissue morphology; Numbers; Oklahoma; Property; Prophylactic treatment; Research; Research Personnel; Research Project Grants; Resolution; Resources; Source; Students; Techniques; Technology; Therapeutic; Therapy Evaluation; United States National Institutes of Health; Urea; Vascularization; angiogenesis; base; bioimaging; clinical application; in vivo; nitrone; prevent; relating to nervous system; success; therapeutic effectiveness; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is focused on the use of in vivo magnetic resonance (MR) techniques, magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) for the serial in vivo detection of intracranial brain tumor biomarkers in experimental animal glioma models, and the assessment of phenyl tert-butyl nitrone (PBN) in its ability to suppress malignant glioma formation. Our hypothesis is that PBN, which has antioxidant, anti-inflammatory properties, can be used to inhibit the formation of malignant gliomas. Specifically, we are using high resolution in vivo functional MRI and MRS methods to monitor changes in vascularization and neuronal metabolites, as tumor biomarkers, to evaluate the effectiveness of PBN in preventing malignant brain tumor formation. The success of this research project serves as the basis for the evaluation of potential compounds that may be useful as therapeutic and/or prophylaxis agents that can reduce the formation of malignant gliomas in humans. Our results show that high resolution in vivo MR angiography provides useful information on vascularization differences between normal tissues and tumors, and we have found that gliomas have increased angiogenesis. Also functional MRS methods can monitor changes in neuronal metabolites in gliomas, such as an increase in lipids, and decreases in Cho (choline), Cr (total creatine), and NAA (N-acetyl aspartate). PBN has been found to inhibit these changes in angiogenesis (MRA) and in neural metabolites (MRS). Four glioma models have been investigated (C6, F98, 9L/lacZ and ENU (ethyl nitroso urea). The ENU model was found to be unreliable for PBN treatment studies due to the low number of animals presenting gliomas. The MRI Facility at OMRF allows cutting edge in vivo technology to be used for both the diagnosis as well as the assessment of the therapeutic effectiveness of potential agents in preventing malignant glioma formation. The technology can also eventually be adapted for clinical use. It is anticipated that the proposed basic research, and future clinical applications will develop into a neurological cancer MRI network in and contribute to the Oklahoma Center for Neuroscience network. In addition, graduate students are currently participating in the use of biomedical imaging for tumor detection and therapy evaluation.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目主要利用活体磁共振（MR）技术、磁共振波谱（MRS）和磁共振成像（MRI）技术，在实验动物脑胶质瘤模型中进行颅内肿瘤生物标志物的系列活体检测，并评估苯基叔丁基硝酮（PBN）抑制恶性胶质瘤形成的能力。 我们的假设是PBN具有抗氧化、抗炎的特性，可用于抑制恶性胶质瘤的形成。 具体而言，我们正在使用高分辨率的体内功能性MRI和MRS方法来监测血管化和神经元代谢物的变化，作为肿瘤生物标志物，以评估PBN在预防恶性脑肿瘤形成中的有效性。 该研究项目的成功为评价可能用作治疗和/或预防剂的潜在化合物提供了基础，这些化合物可以减少人类恶性胶质瘤的形成。 我们的研究结果表明，高分辨率的在体磁共振血管造影提供了有用的信息之间的血管正常组织和肿瘤的差异，我们已经发现，胶质瘤血管生成增加。 功能性MRS方法还可以监测神经胶质瘤中神经元代谢物的变化，例如脂质的增加，以及Cho（胆碱）、Cr（总肌酸）和NAA（N-乙酰天冬氨酸）的减少。 已发现PBN抑制血管生成（MRA）和神经代谢物（MRS）中的这些变化。 已经研究了四种胶质瘤模型（C6、F98、9 L/lacZ和ENU（乙基亚硝基脲））。 由于出现神经胶质瘤的动物数量较少，因此发现ENU模型对于PBN治疗研究不可靠。 OMRF的MRI设施允许尖端的体内技术用于诊断以及评估潜在药物预防恶性胶质瘤形成的治疗效果。这项技术最终也可以用于临床。 预计拟议的基础研究和未来的临床应用将发展成为一个神经系统癌症MRI网络，并有助于俄克拉荷马州神经科学中心网络。 此外，研究生目前正在参与使用生物医学成像进行肿瘤检测和治疗评估。