Free Radical Metabolism and Imaging

项目总结/摘要 在过去的二十年里，大量的证据表明，代谢氧化/还原 反应代表了促进和进展的重要潜在机制， 恶性肿瘤，以及用于选择性地使癌细胞对治疗干预敏感的治疗靶标 以及保护正常组织免受常规细胞毒性疗法的影响。与此同时， 认识到先进的医学成像技术，测量癌症与正常人的代谢变化， 治疗前和治疗期间的组织在允许非侵入性定量和监测 癌细胞代谢的根本差异，以改善癌症治疗。最重要的假设是 自由基代谢和成像（FRMI）计划是癌细胞存在于一种慢性状态， 代谢性氧化应激，代表促进和 以及用于使肿瘤细胞对治疗敏感的治疗靶点， 防止正常组织损伤。此外，功能成像技术测量代谢 肿瘤相对于正常组织的变化已经显示出作为预测因子和生物标志物的巨大前景， 用于改善癌症治疗。这一独特计划的成员包括33名正式成员， 代表两所书院及九个学系的五名准会员。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， 新的图像引导癌症治疗和诊断/预后的基于机制的生化原理 工具. FRMI成员具有高度协作性。在上一次支持期间，235名癌症患者中有83% 相关出版物是合作出版的，包括75份（32%）方案内出版物，83份（35%）方案间出版物 127篇（54%）机构间出版物，包括17篇高影响力（影响因子>10）期刊。程序 成员癌症研究获得了370万美元的直接同行评审资金支持，其中包括210万美元 在CCSG支持的最后一年，NCI资助。富有成效的方案内/方案间和机构间 一些研究小组在开发抗坏血酸作为癌症辅助药物方面取得了领先的进展 由新的NCI P01支持的治疗，用于保护正常组织的超氧化物歧化酶模拟物 毒性和肽靶向的、基于放射性核素的治疗不确定性治疗。

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.