GENE AND CYTOKINE EXPRESSION IN THE CNS RADIORESPONSE

CNS 放射反应中的基因和细胞因子表达

基本信息

批准号：
6192929
负责人：
Philip Tofilon
金额：
$ 20.82万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2001-06-15
项目状态：
已结题

项目摘要

The rational development of strategies for preventing or treating radiation injury in the central nervous system (CNS) will require a more complete understanding of the fundamental radiobiology of this critical normal tissue. After other types of CNS injury acute cell death is followed by the activation of secondary reactive processes that occur hours to days after the initial damage and contribute to lesion development. In addition, there is the activation of repair/recovery processes involving the induction of genes coding for a variety of protective cytokines. The working hypothesis of this proposal is that a similar scheme applies to the CNS injury induced by radiation. Proposed studies will address the induction of repair/recovery mechanisms and the activation of secondary processes that contribute to injury development. Regarding the activation of protective mechanisms, the focus will be on the transcription factor NF-kB. Radiation-induced activation of NF-kB in the CNS is followed by a refractory period during which the susceptibility of this transcription factor to activation by subsequent irradiation is significantly reduced. An aim of this proposal is to define the mechanisms that regulate radiation-induced NF-kB activation and to determine its significance in the radioresponse of the CNS. Regarding secondary processes, an aim is to define the incidence of oxidative stress in the rat spinal cord after irradiation. To address the significance of oxidative stress in radiation CNS injury, the effects of specific anti-oxidants on radiation-induced myelopathy will be investigated. Finally, mitochondrial function and metabolism will be investigated in primary cell cultures and in the spinal cord after irradiation. The hypothesis to be tested is that mitochondrial damage serves as a source of oxidative stress and contributes to the development of radiation injury. It is anticipated that delineating the secondary events that contribute to tissue injury and the intrinsic protection mechanisms will lead to identification of processes subject to manipulation and thus provide the basis for developing therapies for radiation induced CNS toxicity.

合理制定预防或治疗策略中枢神经系统（CNS）的辐射损伤需要更多的治疗完全了解这一关键正常的基础放射生物学组织。其他类型的中枢神经系统损伤后，急性细胞死亡次生反应过程的激活发生在数小时至数天后初始损伤并促进病变发展。此外，还有修复/恢复过程的激活涉及基因编码的诱导对多种保护性细胞因子。本提案的工作假设类似的方案适用于辐射引起的中枢神经系统损伤。拟议的研究将解决修复/恢复机制的诱导和导致损伤发展的次级过程的激活。关于保护机制的激活，重点是转录因子 NF-kB。辐射诱导的中枢神经系统 NF-kB 激活是随后是一个不应期，在此期间，这种情况的敏感性随后的照射对转录因子的激活作用显着减少。该提案的目的是定义监管机制辐射诱导的 NF-kB 激活并确定其在中枢神经系统的放射反应。关于二次过程，目标是定义辐射后大鼠脊髓氧化应激的发生率。到解决氧化应激在辐射中枢神经系统损伤中的重要性，特定抗氧化剂对辐射诱发的脊髓病的影响调查了。最后，线粒体功能和代谢将在原代细胞培养物和辐射后的脊髓中进行了研究。要测试的假设是线粒体损伤是氧化应激并导致辐射损伤的发生。这是预计描绘出有助于组织的次生事件损伤和内在保护机制将导致识别过程受到操纵，从而为开发提供基础治疗辐射引起的中枢神经系统毒性。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

X-ray-mediated reduction in basic fibroblast growth factor expression in primary rat astrocyte cultures.

X射线介导的原代大鼠星形胶质细胞培养物中碱性成纤维细胞生长因子表达的减少。

DOI：
发表时间：
1997
期刊：
Radiation research
影响因子：
3.4
作者：
Noel,F;Ijichi,A;Chen,JJ;Gumin,GJ;Tofilon,PJ
通讯作者：
Tofilon,PJ

IkappaBalpha degradation is not a requirement for the X-ray-induced activation of nuclear factor kappaB in normal rat astrocytes and human brain tumour cells.

在正常大鼠星形胶质细胞和人脑肿瘤细胞中，X 射线诱导的核因子 kappaB 激活不需要 IkappaBalpha 降解。

DOI：
10.1080/095530098141195
发表时间：
1998
期刊：
International journal of radiation biology
影响因子：
2.6
作者：
Raju,U;Gumin,GJ;Noel,F;Tofilon,PJ
通讯作者：
Tofilon,PJ

Microglial cytokine gene induction after irradiation is affected by morphologic differentiation.

DOI：
发表时间：
1997-11
期刊：
Radiation medicine
影响因子：
0
作者：
K. Hayakawa;P. Borchardt;S. Sakuma;A. Ijichi;H. Niibe;P. Tofilon
通讯作者：
K. Hayakawa;P. Borchardt;S. Sakuma;A. Ijichi;H. Niibe;P. Tofilon

Salen Mn complexes mitigate radiation injury in normal tissues.

DOI：
10.2174/187152011795677490
发表时间：
2011-05-01
期刊：
Anti-cancer agents in medicinal chemistry
影响因子：
2.8
作者：
Rosenthal RA;Fish B;Hill RP;Huffman KD;Lazarova Z;Mahmood J;Medhora M;Molthen R;Moulder JE;Sonis ST;Tofilon PJ;Doctrow SR
通讯作者：
Doctrow SR

Failure of a second X-ray dose to activate nuclear factor kappaB in normal rat astrocytes.

第二次 X 射线剂量未能激活正常大鼠星形胶质细胞中的核因子 kappaB。