Free Radical Metabolism and Imaging

自由基代谢和成像

• 批准号: 10600132
• 负责人: Douglas Robert Spitz
• 金额: $ 3.55万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-14 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600132
• 关键词: Adjuvant; Algorithms; Biochemical; Biochemistry; Biological Markers; Cancer Biology; Cancer Center Support Grant; Cancer Diagnostics; Chronic; Cytotoxic Chemotherapy; Development; Discipline; Epigenetic Process; Free Radicals; Functional Imaging; Funding; Genetic; Head and Neck Cancer; Image; Imaging Techniques; Imaging technology; Institution; Journals; Malignant Neoplasms; Measures; Medical Imaging; Metabolic; Metabolism; Monitor; Neuroendocrine Tumors; Normal Cell; Normal tissue morphology; Oxidation-Reduction; Oxidative Stress; Patient-Focused Outcomes; Peer Review; Peptides; Pharmacologic Ascorbate; Phase III Clinical Trials; Productivity; Publications; Radio; Radioisotopes; Reaction; Research; Research Personnel; Science; Signal Transduction; Superoxide Dismutase; Testing; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; Tumor Biology; Work; anticancer research; biomarker development; cancer cell; cancer therapy; college; image guided; imaging platform; imaging program; improved; inter-institutional; member; metabolic imaging; mimetics; neoplastic cell; novel; oral mucositis; oxidation; prognostic tool; programs; theranostics; therapeutic target; therapy outcome; tissue injury; translational study; tumor; tumor metabolism

PROJECT SUMMARY/ABSTRACT During the past two decades a significant body of evidence has shown that metabolic oxidation/reduction reactions represent a significant underlying mechanism contributing to promotion and progression of malignancy, as well as a therapeutic target for selectively sensitizing cancer cells to therapeutic interventions and protecting normal tissues from conventional cytotoxic therapies. Evolving in parallel has been the recognition that advanced medical imaging techniques, measuring metabolic changes in cancer versus normal tissues before and during therapy show great promise in allowing non-invasive quantitation and monitoring of fundamental differences in cancer cell metabolism to improve cancer therapy. The overarching hypothesis in the Free Radical Metabolism and Imaging (FRMI) program is that cancer cells exist in a chronic state of metabolic oxidative stress that represents a significant underlying mechanism contributing to promotion and progression of malignancy as well as a therapeutic target for sensitizing tumor cells to therapy as well as protecting against normal tissue injury. Furthermore, functional imaging techniques measuring metabolic changes in tumors versus normal tissues have shown great promise as predictors and biomarkers that can be used to improve cancer therapy. The diverse membership of this unique program includes 33 full members and five associate members representing two colleges and nine departments. These investigators work together to take full advantage of the convergence of the science in these two related disciplines for developing a mechanism based biochemical rationale for new image-guided cancer therapies and diagnostic/prognostic tools. FRMI members are highly collaborative. During the last period of support, 83% of a total of 235 cancer relevant publications were collaborative including 75 (32%) intraprogrammatic, 83 (35%) interprogrammatic and 127 (54%) interinstitutional publications including 17 in high impact (Impact Factor >10) journals. Program member cancer research was supported by $3.7 million of direct peer-reviewed funding including $2.1 million of NCI funding in the last year of CCSG support. Productive intra/interprogrammatic and interinstitutional groups are leading advances in the development of pharmacological ascorbate as an adjuvant to cancer therapy supported by a new NCI P01, superoxide dismutase mimetics for protection of normal tissues toxicities, and peptide-targeted, radionuclide-based theragnostic treatments.

项目摘要/摘要 在过去的二十年里，大量证据表明新陈代谢氧化/还原 反应是促进和发展的一个重要的潜在机制 恶性肿瘤，以及选择性地使癌细胞对治疗干预敏感的治疗靶点 以及保护正常组织免受常规细胞毒疗法的影响。与之平行发展的是 认识到先进的医学成像技术，测量癌症与正常人群的代谢变化 治疗前和治疗期间的组织显示出很大的希望，可以无创地定量和监测 肿瘤细胞代谢的根本差异，以提高癌症治疗。中的首要假设 自由基代谢和成像(FRMI)计划是癌细胞以慢性状态存在 代谢性氧化应激，代表了促进和 恶性肿瘤的进展以及使肿瘤细胞对治疗敏感的治疗靶点 保护身体免受正常组织损伤。此外，功能成像技术测量新陈代谢 肿瘤与正常组织相比的变化已显示出作为预测和生物标记物的巨大前景 用于改善癌症治疗。这一独特计划的不同成员包括33名正式成员和 代表两个学院和九个系的五名准成员。这些调查人员共同努力 充分利用这两个相关学科的科学融合，开发一种 基于机制的新的影像引导癌症治疗和诊断/预后的生化原理 工具。FRMI成员具有高度的协作性。在最后一段时间的支持期间，总共235例癌症患者中有83% 相关出版物是协作性的，包括75份(32%)方案内出版物，83份(35%)方案间出版物 机构间出版物127篇(54%)，其中17篇发表在高影响力(影响因素)期刊上。计划 成员癌症研究得到了370万美元的直接同行评审资金的支持，其中包括210万美元 在CCSG支持的最后一年中，NCI的资金。富有成效的方案内/方案间和机构间 在抗坏血酸作为癌症佐剂的药理开发方面，小组是领先的进展 一种新的NCI P01，超氧化物歧化酶模拟物支持的保护正常组织的治疗 毒性和多肽靶向、基于放射性核素的治疗。