Intracellular Radiation as a Novel Approach for Infection Treatment

细胞内放射作为感染治疗的新方法

• 批准号: 7740532
• 负责人: JUN F LIANG
• 金额: $ 19.13万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740532
• 关键词: Affect; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antineoplastic Agents; Bacteria; Bacterial DNA; Bacterial Infections; Binding; Cessation of life; Chemotherapy-Oncologic Procedure; Cytoplasm; DNA; DNA Binding; DNA Damage; DNA Repair; Disease; Dose; Drug Exposure; Drug resistance; Electrons; External Beam Radiation Therapy; Genes; Goals; Grant; Health; Human; In Vitro; Infection; Ionizing radiation; Left; Lighting; Linear Energy Transfer; Maintenance; Malignant Neoplasms; Production; Proteins; Radiation; Reactive Oxygen Species; Relapse; Research; Resistance; System; Testing; Time; adduct; bacterial resistance; cancer cell; cancer therapy; chemotherapy; clinical application; design; fighting; improved; killings; macromolecule; novel; novel strategies; pressure; public health relevance; radiation resistance; success; treatment strategy; tumor

DESCRIPTION (provided by applicant): Despite attractive, ionizing radiations cannot be directly applied in the treatment of bacterial infections since bacteria are extremely insensitive to radiations. The lethal radiation dose for bacteria is at least 1,000 times higher than the whole-body lethal dose for human. In this R21 project, we propose a novel intracellular radiation approach to activate a secondary and local radiation inside of bacteria to damage chromosomal DNAs selectively and specifically. The underlying hypothesis of this project is that: this intracellular radiation can overcome the radiation resistance in bacteria, and the intracellular radiation by itself or in combination with antibiotics may become an effective means to kill antibiotic resistance bacteria. The primary goal of this grant is to achieve the "proof-of-concept" via well designed in vitro studies. The success of this project may provide a new approach for improved the treatment of bacterial infections and various infection related diseases. PUBLIC HEALTH RELEVANCE: Intracellular Radiation as a Novel Approach for Infection Treatment Narrative Bacteria is resistant to ionizing radiations. The lethal radiation dose (1,000 Gy to 6,000 Gy) for bacteria is far beyond the whole-body lethal dose for human (5 Gy) and thus limits the potential applications of ionizing radiation in the treatment of antibiotics resistance. In this project, we propose a novel intracellular radiation approach to overcome the radiation resistance in bacteria and explore the clinical applications of radiations in the treatment of bacterial infections and various infection related diseases.

描述(申请人提供)：尽管具有吸引力，但由于细菌对辐射极其不敏感，电离辐射不能直接应用于细菌感染的治疗。细菌的致死辐射剂量至少是人类全身致死剂量的1000倍。在这个R21项目中，我们提出了一种新的细胞内辐射方法，以激活细菌内部的二次和局部辐射，选择性和特异性地损伤染色体DNA。该项目的基本假设是：这种细胞内辐射可以克服细菌对辐射的抵抗力，而细胞内辐射本身或与抗生素联合使用可能成为杀灭抗生素耐药细菌的有效手段。这笔赠款的主要目标是通过精心设计的体外研究来实现“概念验证”。该项目的成功可能为改进细菌感染和各种感染相关疾病的治疗提供一种新的途径。公共卫生相关性：细胞内辐射作为一种新的感染治疗方法，叙述了细菌对电离辐射的抵抗力。电离辐射对细菌的致死剂量(1000~6000 Gy)远远超过对人体的全身致死剂量(5 Gy)，从而限制了电离辐射在治疗抗生素耐药性方面的潜在应用。在这个项目中，我们提出了一种新的细胞内辐射方法来克服细菌对辐射的抵抗力，并探索了辐射在治疗细菌感染和各种感染相关疾病中的临床应用。