Free Radical Cancer Biology

自由基癌生物学计划(FRCBP)是HCCC独有的，专注于研究癌症和正常细胞之间还原和氧化(Redox)代谢固有差异的生物学。 该项目的研究正在确定氧化还原反应在与细胞生长、分化、信号转导、转移、功能分子成像和治疗相关的癌症表型变化中所起的作用。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，为改进癌症治疗开发新的生化原理。该计划有三个重叠的主题。主题1：了解氧化还原生物化学在调节与癌症生物学相关的遗传和表观遗传基因表达途径中的作用。在这一主题中，重点研究领域是探索全球氧化还原波动和基因表达，以及与关键氧化还原敏感分子相关的基因表达变化，如谷胱甘肽、硫氧还蛋白、超氧化物歧化酶和AP2。论文2：理解氧化还原调节在细胞生物学中的作用。在这个主题中，有一些研究领域探索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。在这个主题中，有一些研究领域探索了操纵氧化应激对 改善治疗，并使用氧化代谢成像作为监测和指导治疗的方法。FRCBP在过去资助期间的主要成就包括：(A)癌细胞(相对于正常细胞)从线粒体代谢产生的02*‘和H_2O_2的稳态水平增加，这对葡萄糖诱导的克隆细胞杀伤的不同敏感性有显著贡献 被剥夺；(B)细胞外超氧化物歧化酶(EcSOD)抑制侵袭和转移；(C)MnSOD的表达控制辐射后活性氧的晚期产生、细胞周期检查点和转化；(D)葡萄糖和氢过氧化氢代谢的抑制剂可用于 通过增强代谢氧化应激来增强对放化疗的反应。FRCBP由来自1个基础科学系、6个临床科和2个学院的18名成员组成。经过同行评审，该项目的研究资金总额为390万美元，其中NCI的总成本超过200万美元。FRCBP成员共同撰写了237份出版物。在这些出版物中，20%是方案内出版物，24%是方案内出版物 方案间出版物和10%的出版物既是方案内出版物，也是方案间出版物，总共有54%的合作出版物。

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.