Post-Irradiation Intervention to Mitigate and Treat Non Hematological Radiation

减轻和治疗非血液放射的放射后干预

• 批准号: 7925109
• 负责人: JOHN E MOULDER
• 金额: $ 28.41万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925109
• 关键词: Post; Irradiation; Intervention; Mitigate; Treat

The overall goal of the Center is to develop pharmacologic approaches for the mitigation and treatment of the non-hematological radiation injuries that will occur in victims of radiological terrorism or radiation accidents who receive doses in excess of 5 Gy, and for whom hematological toxicity is prevented or avoided. For uniform total body irradiation, injury to bone marrow is likely to be the primary life-threatening injury. But for partial-body exposure or for internally-deposited radioisotopes (where radiation doses may be high but some bone marrow may be spared), or if the bone marrow damage can be treated with cytokines or stem cell transplants, other types of acute (e.g., Gl, skin, lung) and late (e.g. renal, lung, CNS) injuries are expected to occur. It is these non-hematological injuries which are the focus of the proposed Center; although treatment and mitigation of injuries to these tissues will be of little importance to victims of radiological terrorism or radiation accidents unless there are advancements in the mitigation and treatment of hematological injuries. The Center will be a Consortium made up of 5 projects and 5 cores drawn from 4 institutions: the Medical College of Wisconsin, the Henry Ford Health Systems, the University of Toronto, and Eukarion, Inc. The organ systems to be studied are the Gl tract (Project 1), the kidney (Project 2), the lung (Projects 3 and 4) and the CNS (Project 5), as these are some of the major organ systems that will be at risk if doses exceed 5 Gy and if fatal hematological injury is prevented or avoided. The rodent radiation-induced renal injury model system used in Project 2 and the canine model for Gl injury (Project 1) are already well-developed; but further model development is required for large-animal renal models (Project 2), and for rodent models of Gl injury (Project 1), lung injury (Projects 3 and 4) and CNS injury (Project 5). The major pharmaceutical approaches that will be assessed are suppression of the renin-angiotensin system (Projects 1, 2, 3, 5), and suppression of acute and chronic oxidative stress (Projects 1, 2, 4, 5). The Projects will be supported by an Irradiation Core and a SOD/Catalase Mimetic Core; and the Center will also contain a Pilot Grant Program and a Teaching and Education Program).

该中心的总体目标是开发药理学方法，以减轻和治疗辐射恐怖主义或辐射事故受害者在接受超过5戈伊的剂量时可能发生的非血液辐射损伤，并预防或避免血液毒性。对于均匀全身照射，骨髓损伤可能是主要的危及生命的损伤。但对于部分身体暴露或内部沉积的放射性同位素（其中辐射剂量可能很高，但一些骨髓可能不会受到影响），或者如果骨髓损伤可以用细胞因子或干细胞移植治疗，则其他类型的急性（例如，GI、皮肤、肺）和晚期（例如肾、肺、CNS）损伤。这些非血液损伤是拟议中心的重点;虽然治疗和减轻这些组织的损伤对放射性恐怖主义或辐射事故的受害者来说并不重要，除非在减轻和治疗血液损伤方面取得进展。该中心将是一个由来自4个机构的5个项目和5个核心组成的联盟：威斯康星州医学院、亨利福特卫生系统、多伦多大学和Eukarion公司。待研究的器官系统是胃肠道（项目1）、肾脏（项目2）、肺（项目3和4）和CNS（项目5），因为如果剂量超过5戈伊，并且如果预防或避免致命的血液学损伤，这些是将处于风险中的一些主要器官系统。项目2中使用的啮齿动物辐射诱导的肾损伤模型系统和GI损伤的犬模型（项目1）已经开发良好;但需要进一步开发大型动物肾模型（项目2）以及GI损伤（项目1）、肺损伤（项目3和4）和CNS损伤（项目5）的啮齿动物模型。将评估的主要药物方法是抑制肾素-血管紧张素系统（项目1、2、3、5）以及抑制急性和慢性氧化应激（项目1、2、4、5）。这些项目将得到辐照核心和SOD/过氧化氢酶模拟核心的支持;该中心还将包含一个试点赠款计划和一个教学和教育计划。

项目成果

Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung.

• DOI: 10.1667/rr3127.1
• 发表时间: 2013-04
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Gao F;Narayanan J;Joneikis C;Fish BL;Szabo A;Moulder JE;Molthen RC;Jacobs ER;Rao RN;Medhora M
• 通讯作者: Medhora M

Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril.

• DOI: 10.1111/j.1440-1843.2012.02247.x
• 发表时间: 2012-11
• 期刊: Respirology (Carlton, Vic.)
• 作者: Molthen RC;Wu Q;Fish BL;Moulder JE;Jacobs ER;Medhora MM
• 通讯作者: Medhora MM

Novel synthetic SOD/catalase mimetics can mitigate capillary endothelial cell apoptosis caused by ionizing radiation.

• DOI: 10.1667/rr1948.1
• 发表时间: 2010-06
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Vorotnikova E;Rosenthal RA;Tries M;Doctrow SR;Braunhut SJ
• 通讯作者: Braunhut SJ

Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation.

• DOI: 10.1667/rr2400.1
• 发表时间: 2011-01
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Moulder JE;Cohen EP;Fish BL
• 通讯作者: Fish BL

Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.

• DOI: 10.1186/1748-717x-3-40
• 发表时间: 2008-11-24
• 期刊: RADIATION ONCOLOGY
• 影响因子: 3.6
• 作者: Kumar, Sanath;Kolozsvary, Andrew;Kohl, Robert;Lu, Mei;Brown, Stephen;Kim, Jae Ho
• 通讯作者: Kim, Jae Ho