Free Radical Cancer Biology Program

自由基癌症生物学计划

基本信息

批准号：
7900743
负责人：
Douglas Robert Spitz
金额：
$ 1.96万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7900743
关键词：
Age Aging Animal Model Animals Antineoplastic Agents Antioxidants Area Arts Basic Science Biology Breast Cancer Cell Buffers Cancer Biology Cancer Center Cancer Center Support Grant Cardiac Cells Clinical Collaborations DNA Methylation Dimensions Disease Doxorubicin Enzymes Event Faculty Fever Free Radicals Funding Gene Expression Goals Grant Growth Human Individual Inhalation Drug Administration Learning Link Maintenance Malignant - descriptor Malignant Neoplasms Medicine Methods Modification Neoplasm Metastasis Neoplasms Nitric Oxide Oral Oxidants Oxidation-Reduction Peroxides Pharmaceutical Preparations Phospholipids Photochemotherapy Predisposition Program Research Project Grants Radiation Research Research Activity Research Peer Review Research Personnel Role Science Signal Transduction Transfection United States National Institutes of Health acute stress cancer initiation cancer therapy cell type college cytotoxicity effective therapy glutathione peroxidase improved interest malignant mouth neoplasm member neoplastic older patient oxidation programs

项目摘要

Research in the Free Radical Cancer Biology Program focuses on oxidative events in cancer, including free radicals, cell redox state and effects of anticancer drugs, radiation and other types of anticancer therapy. The overall goals of the members of this program are to identify ways of manipulating cellular redox state to improve cancer therapy and to understand the changes in oxidation associated with neoplastic disease. There are four major overlapping themes within the Program's research. Theme 1 - Understanding the role of oxidative and nitrosative events and signaling in cancer biology. Theme 2 - Augmenting cancer therapy using modulation of antioxidant enzymes, free radicals or oxidative strategies Theme 3 - The role of nitric oxide in cancer biology and cancer treatment Theme 4 - Understanding why neoplasia is more frequent and sometimes has a different biology as we age. The major accomplishments of the Free Radical Cancer Biology Program over the past funding period include the findings that (a) AdMnSOD transduction is an effective treatment for animal models of human oral cancer, (b) nitric oxide augments cell cytotoxicity of doxorubicin for a malignant breast cancer cell, but not for a cardiac cells, (c) there is a role for DNA methylation in the establishment and/or maintenance of cell-type specific gene expression, (d) there is a blunted ability in old animals to buffer potentially harmful oxidants being produced within a cell following an acute stress, and (e) that the antioxidant enzyme phospholipid glutathione peroxidase influences the growth rate of cells by altering the peroxide tone. There are numerous past and present productive collaborations both between members of the Program, and with members of other Cancer Center programs. For example, the Program Project Grant in Oxidative Events in Cancer Therapy and our participation in the Aging and Cancer P20 involve many members and are highly interactive and programmatic. The Free Radical Cancer Biology Program consists of 17 members from 9 departments and 2 colleges. Peer-reviewed, research funding for this program totals $2,230,523 with $1,624,781 coming from the NCI.

自由基癌症生物学项目的研究重点是癌症中的氧化事件，包括自由基、细胞氧化还原状态以及抗癌药物、放射和其他类型抗癌疗法的影响。该计划成员的总体目标是确定操纵细胞氧化还原状态以改善癌症治疗的方法，并了解与肿瘤疾病相关的氧化变化。该计划的研究中有四个主要的重叠主题。主题 1 - 了解氧化和亚硝化事件以及信号传导在癌症生物学中的作用。主题 2 - 使用抗氧化酶、自由基或氧化策略的调节增强癌症治疗主题 3 - 一氧化氮在癌症生物学和癌症治疗中的作用主题 4 - 了解为什么随着年龄的增长，肿瘤更常见，并且有时具有不同的生物学特征。自由基癌症生物学计划在过去资助期间的主要成就包括以下发现：(a) AdMnSOD 转导是人类口腔癌动物模型的有效治疗方法， (b) 一氧化氮增强阿霉素对恶性乳腺癌细胞的细胞毒性，但不能增强阿霉素对乳腺癌细胞的细胞毒性。 (c) DNA 甲基化在细胞类型特异性基因表达的建立和/或维持中发挥作用，(d) 年老动物缓冲细胞内产生的潜在有害氧化剂的能力减弱急性应激，以及（e）抗氧化酶磷脂谷胱甘肽过氧化物酶通过改变过氧化物调来影响细胞的生长速率。该计划的成员之间以及与其他癌症中心计划的成员之间过去和现在都有许多富有成效的合作。例如，癌症治疗中的氧化事件项目资助以及我们对老龄化和癌症 P20 的参与涉及许多成员，并且具有高度互动性和计划性。自由基癌症生物学项目由来自 9 个系和 2 个学院的 17 名成员组成。经同行评审，该项目的研究经费总计 2,230,523 美元，其中 1,624,781 美元来自 NCI。