Program 3: Free Radical Metabolism and Imaging

项目 3：自由基代谢和成像

• 批准号: 9252418
• 负责人: Douglas Robert Spitz
• 金额: $ 2.58万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9252418
• 关键词: Adjuvant; Animals; Biochemistry; Biology; Biostatistics Core; Bone Marrow; Cancer Biology; Cancer Center; Cancer Center Support Grant; Cancer Patient; Carboxylic Acids; Cell Cycle; Chronic; Clinical; Clinical Trials; Collaborations; Decision Making; Development; Diagnosis; Diagnostic Imaging; Discipline; Discipline of Nuclear Medicine; Epigenetic Process; Evaluation; FOLH1 gene; Faculty; Family suidae; Flow Cytometry; Free Radicals; Functional Imaging; Funding; Genetic; Genome Stability; Genomics Shared Resource; Goals; Head and Neck Cancer; Image; Imaging Techniques; Injury; Institution; Ions; Journals; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Mammalian Cell; Manuscripts; Measures; Medical Imaging; Medical Oncologist; Metabolic; Metabolism; Microscopy; Misonidazole; Mitochondria; Molecular; Monitor; Neoplasm Metastasis; Neuroendocrine Tumors; Neurosecretory Systems; New Agents; Normal Cell; Normal tissue morphology; Octreotide; Oxidation-Reduction; Oxidative Stress; Patient-Focused Outcomes; Peer Review; Pelvic Cancer; Pharmacology; Phase I Clinical Trials; Physicians; Play; Positron-Emission Tomography; Publications; Publishing; Radiation; Radiation Oncologist; Research; Research Personnel; Resource Sharing; Resources; Role; SOD2 gene; Science; Scientist; Signal Transduction; Sirtuins; Surgical Oncologist; Testing; Therapeutic; Therapeutic Intervention; Transgenic Animals; United States; Viral Vector; Work; anatomic imaging; anticancer research; ascorbate; base; cancer cell; cancer diagnosis; cancer imaging; cancer therapy; chemoradiation; chemotherapy; college; head and neck cancer patient; image guided therapy; imaging program; imaging study; improved; ketogenic diet; member; metabolic imaging; molecular imaging; novel; novel strategies; pre-clinical; predict clinical outcome; predicting response; programs; radiation response; research facility; response; therapeutic development; therapeutic target; therapy outcome; tumor; tumor metabolism

During the past two decades a significant body of evidence has accumulated showing 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. 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 Free Radical Metabolism and Imaging (FRMI) Program (32 full members and 9 associate members) representing 3 colleges and 10 departments was formed by a merger in 2014 of former programs in Free Radical Cancer Biology and Tumor Imaging to take full advantage of the convergence of the science in these two disciplines. The FRMI program has four research themes: 1) Free Radical Cancer Biology, the study of fundamental differences in redox biochemistry and its impact on cell signaling, genetics and epigenetics in cancer biology and therapy; 2) Redox-Based Therapeutics, the development and testing of novel cancer therapeutics based on exploiting fundamental differences in free radical metabolism to selectively eradicate cancer cells while protecting normal tissues; 3) Patient Outcomes and Molecular Imaging, the development of novel image- guided therapy approaches for enhancing and predicting patient outcomes in cancer therapy using molecular and metabolic imaging techniques; and 4) Novel Approaches to Diagnostic Imaging, the development of novel approaches that integrate state-of-the-art functional and anatomic imaging techniques into cancer biology and therapy. FRMI members were highly collaborative during the last period of support with a total of 250 cancer relevant publications (2011-2015) including 53% (n=133) involving collaborations between 2 or more members of the HCCC. Of the collaborative publications, 66% (n=88) were intra-programmatic and 60% (n=81) were inter- programmatic. In addition, 30% (n=76) were interinstitutional with members of the program co-authoring 45 publications with faculty members at other cancer centers in the United States. Ten manuscripts were published in high impact journals (impact factor ≥10). The program members were supported by $5,857,820 of total peer-reviewed funding and $2,699,266 of NCI funding in the last year of CCSG support. The successful completion of the research initiatives pursued by FRMI would involve preclinical and clinical verification of a paradigm shifting approach for targeting oxidative metabolic processes in cancer cells as indicated by selective enhancement of therapeutic outcomes, and implementation of new image-based approaches to predicting clinical outcomes, monitoring response and guiding decision-making.

在过去的二十年里，大量的证据表明，代谢 氧化/还原反应代表了有助于促进的重要潜在机制， 恶性肿瘤的进展，以及用于选择性地使癌细胞对治疗剂敏感的治疗靶点 干预措施。与此同时，人们认识到，先进的医学成像技术， 在治疗前和治疗期间测量癌症与正常组织的代谢变化显示出很大的希望 在允许非侵入性定量和监测癌细胞代谢的基本差异， 改善癌症治疗。自由基代谢和成像（FRMI）计划（32名正式成员和9名 准会员）代表3个学院和10个部门成立于2014年合并的前 自由基癌症生物学和肿瘤成像计划，以充分利用 这两个学科的科学。 FRMI计划有四个研究主题：1）自由基癌症生物学，基础研究 氧化还原生物化学的差异及其对癌症生物学中细胞信号传导、遗传学和表观遗传学的影响 2）基于氧化还原的治疗，开发和测试基于氧化还原的新型癌症治疗方法 利用自由基代谢的根本差异来选择性地根除癌细胞， 保护正常组织; 3）患者结局和分子成像，开发新的图像- 使用分子生物学技术增强和预测癌症治疗中患者结果的指导治疗方法 和代谢成像技术;和4）诊断成像的新方法，新的 将最先进的功能和解剖成像技术整合到癌症生物学中的方法， 疗法 FRMI成员在上一个支持期间高度合作，共有250名癌症相关患者。 出版物（2011-2015年），包括53%（n=133）涉及2名或更多成员之间的合作 HCCC。在合作出版物中，66%（n=88）为计划内出版物，60%（n=81）为计划间出版物。 纲领性的。此外，30%（n=76）是跨机构的，与该计划的成员共同创作45 与美国其他癌症中心的教职员工一起出版。10篇论文 在高影响力期刊上发表（影响因子≥10）。该计划的成员得到了5，857，820美元的支持， 在CCSG支持的最后一年，同行评审的资金总额和2，699，266美元的NCI资金。成功 完成FRMI所追求的研究计划将涉及临床前和临床验证， 通过选择性代谢试验表明的靶向癌细胞中氧化代谢过程的范式转换方法 提高治疗效果，并实施新的基于图像的方法来预测 临床结果，监测反应和指导决策。