Molecular mechanisms and novel therapeutic approaches to combined radiation and b

放射和b联合治疗的分子机制和新治疗方法

基本信息

批准号：
7568561
负责人：
Roslyn Rivkah ISSEROFF
金额：
$ 19万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-15 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7568561
关键词：
Adrenergic Receptor Adrenergic beta-Antagonists Algorithms Animal Model Animals Apoptosis Architecture Area Arts Biological Assay Biological Markers Biology Biometry Burn injury CREB1 gene Cell Proliferation Cells Clinic Clinical Clinical Sciences Complex Critical Pathways Cytokine Gene Data Development Dose End Point Evaluation Failure Fibroblast Growth Factor Foundations Gene Expression Gene Proteins Genes Genetic Glean HSPB1 gene Harvest Healed Health Benefit Human Impaired wound healing Individual Inflammation Injury Interleukins Intervention Invasive Investigation Ionizing radiation JUN gene Leadership Lesion MAP Kinase Gene MAP2K1 gene MAPK1 gene MAPK14 gene MAPK3 gene MAPK8 gene Measures Mesenchymal Stem Cells Methods Metric Modeling Molecular Molecular Biology Molecular Profiling Mus NF-kappa B Nuclear Warfare Operative Surgical Procedures Outcome Pathway interactions Patients Pattern Pharmaceutical Preparations Phase Proteins Public Health Qualifying RNA ROC Curve Radiation Radiation Injuries Radiobiology Range Safety Sampling Science Skin Skin Tissue Statistical Methods Statistically Significant Surface Surgical wound TP53 gene Testing Time Tissues Trauma Vascular Endothelial Growth Factors Work Wound Healing Wounds and Injuries base beta-adrenergic receptor cost cytokine healing human data improved in vivo injured interest irradiation keratinocyte mouse model multidisciplinary novel therapeutics programs protein expression repaired response success wound

项目摘要

DESCRIPTION (provided by applicant): We will investigate combined injury by moderate dose radiation in two models in a two-phase study. In the first phase, we will use anonymized surgical samples irradiated and wounded ex vivo by burning to study gene and protein expression differences, develop a non-invasive assay to predict successful wound healing, and test a beta adrenergic receptor antagonist as potential therapy to improve wound healing. In the second phase, we will investigate similar issues in a mouse model. Thus, the total study will combine human data (which is, however, not in vivo) and data from intact animals (which is in vivo) to obtain relevant information that can inform the development of a better mechanistic understanding of the mechanisms of wound healing in the presence of radiation damage, and to develop potential therapies that can later be tested in the clinic. Public Health Relevance In a nuclear warfare or terrorist incident, combined injury by radiation and burn wounding is likely. We will provide a better mechanistic understanding of the molecular biology behind healing of combined injury wounds, and will test a non-invasive assay for wound healing success and a potential therapy to improve healing. All of this would be of considerable public health benefit in such a scenario.

描述（由申请人提供）：在两阶段研究中，我们将在两个模型中调查中等剂量辐射的综合损伤。在第一阶段，我们将通过燃烧研究基因和蛋白质表达差异，开发非侵入性测定方法来预测伤口愈合，并测试β肾上腺素能受体拮抗剂作为潜在的治疗，以改善伤口愈合，从而使用匿名的外科手术样品辐照和受伤的离体受伤。在第二阶段，我们将研究鼠标模型中的类似问题。因此，全面研究将结合人类数据（但是，不是体内）和完整动物的数据（体内）的数据，以获取相关信息，以便在存在放射线损害的情况下对伤口愈合机制的发展有助于发展，并开发出可能在诊所进行测试的潜在疗法。公共卫生与核战或恐怖事件中的相关性，可能会因辐射和烧伤伤害而造成的伤害。我们将对损伤联合伤口愈合背后的分子生物学有更好的理解，并将测试一种无创测定的伤口愈合成功和改善愈合的疗法。在这种情况下，所有这些都将带来可观的公共卫生益处。