Free Radical Cancer Biology

自由基癌症生物学

• 批准号: 8340076
• 负责人: George J. Weiner
• 金额: $ 4.8万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-19 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8340076
• 关键词: Area; Arts; Basic Science; Biochemical; Biochemistry; Biology; Cancer Biology; Cancer Center Support Grant; Cell Cycle; Cell Respiration; Cellular biology; Chronic; Clinical; Consensus; Epigenetic Process; Free Radicals; Funding; Gene Expression; Genetic; Glucose; Glutathione; Goals; Hydrogen Peroxide; Image; Individual; Injury; Instruction; Link; Malignant Neoplasms; Medicine; Metabolic; Metabolism; Mitochondria; Monitor; NCI-Designated Cancer Center; Neoplasm Metastasis; Normal Cell; Normal tissue morphology; Oxidation-Reduction; Oxidative Regulation; Oxidative Stress; Pathway interactions; Play; Predisposition; Production; Publications; Radiation; Radio; Reaction; Reactive Oxygen Species; Regulation; Relative (related person); Research; Research Peer Review; Role; Science; Signal Transduction; Superoxide Dismutase; Thioredoxin; Transcription Factor AP-2 Alpha; anticancer research; cancer cell; cancer therapy; cell growth; cell killing; college; cost; deprivation; extracellular; improved; inhibitor/antagonist; interest; member; molecular imaging; novel; programs; response; therapy outcome

The Free Radical Cancer Biology Program (FRCBP) is unique to the HCCC and focuses on studying the biology of inherent differences in reductive and oxidative (redox) metabolism between cancer vs. normal cells. Research in the program is determining the role that redox reactions play in cancer phenotypic changes relevant to cell growth, differentiation, signal transduction, metastasis, functional molecular imaging, and therapy. A unifying goal of the program is to utilize a comprehensive basic science understanding of redox biology to develop novel biochemical rationales for improving cancer therapy. Three overlapping themes exist within the program. Theme 1: Understanding the role of redox biochemistry in regulation of genetic and epigenetic gene expression pathways relevant to cancer biology. Within this theme are research areas of focus exploring redox fluctuations and gene expression globally, as well as gene expression changes related of key redox sensitive molecules such as glutathione, thioredoxin, SOD, and AP2. Ttieme 2: Understanding the role of redox regulation in cell biology. Within this theme are research areas exploring the effects of redox on the cell cycle as well as invasion and metastasis. Ttieme 3: Exploring the role of oxidative stress in therapy outcomes. Within this theme are research areas exploring the role of manipulating oxidative stress to improve therapy as well as using imaging of oxidative metabolism as an approach to monitor and guide therapy. Major accomplishments of the FRCBP over the past funding period include findings that (a) cancer cells (relative to normal cells) produce increased steady-state levels of 02*' and H2O2 from mitochondrial metabolism that significantly contribute to differential susceptibility to clonogenic cell killing induced by glucose deprivation; (b) extracellular superoxide dismutase (EcSOD) inhibits invasion and metastasis; (c) expression of MnSOD governs the late production of reactive oxygen species, cell cycle check points, and transformation following radiation exposure; (d) that inhibitors of glucose and hydroperoxide metabolism can be used to enhance responses to radio-chemo-therapy by enhancing metabolic oxidative stress. The FRCBP consists of 18 members from 1 basic science department and 6 clinical departments and 2 colleges. Peer-reviewed, research funding for this program totals $3.9 million with over $2.0 million total costs from NCI. FRCBP members co-authored 237 publications. Of these publications, 20% were intraprogrammatic, 24% were interprogrammatic and 10% were both intra and interprogrammatic, for a total of 54% collaborative publications.

自由基癌症生物学计划（FRCBP）是HCCC独有的，并着重研究癌症与正常细胞之间还原性和氧化（氧化还原）代谢的固有差异的生物学。 该计划中的研究确定了氧化还原反应在与细胞生长，分化，信号转导，转移，功能性分子成像和治疗相关的癌症表型变化中的作用。该计划的一个统一目标是利用对氧化还原生物学的全面基础科学理解来开发新的生化理由来改善癌症治疗。程序中存在三个重叠的主题。主题1：了解氧化还原生物化学在与癌症生物学相关的遗传和表观遗传基因表达途径调节中的作用。在此主题中，重点的研究领域在全球范围内探索氧化还原波动和基因表达，以及基因表达的变化与关键的氧化还原敏感分子（如谷胱甘肽，硫氧还蛋白，SOD和AP2）相关。 ttieme 2：了解氧化还原调节在细胞生物学中的作用。在此主题中，研究领域探讨了氧化还原对细胞周期以及侵袭和转移的影响。 ttieme 3：探索氧化应激在治疗结果中的作用。在此主题中，研究领域探讨了操纵氧化应激的作用 改善治疗以及使用氧化代谢的成像作为监测和指导治疗的方法。在过去的资金期间，FRCBP的主要成就包括（a）癌细胞（相对于正常细胞）产生的稳态水平增加，从线粒体代谢中产生的02**'和H2O2，这显着促进了对葡萄糖诱导的葡萄糖诱导的差异性的敏感性 剥夺; （b）细胞外超氧化物歧化酶（ECSOD）抑制侵袭和转移； （c）MNSOD的表达控制了活性氧，细胞周期检查点和辐射暴露后转化的晚期产生； （d）葡萄糖和氢过氧代谢的抑制剂可用于 通过增强代谢氧化应激来增强对放射化学疗法的反应。 FRCBP由来自1个基础科学系和6个临床系和2所大学的18名成员组成。同行评审，该计划的研究资金总计390万美元，NCI的总成本超过200万美元。 FRCBP成员合着了237个出版物。在这些出版物中，有20％是磁内图，24％为 分解媒介成分和10％是内部和诠释截图，共有54％的合作出版物。